Smallest Optical Gap for Pt(II)-Pt(IV) Mixed-Valence Pt-Cl and Pt-Br Chain Complexes Achieved by Using a Multiple-Hydrogen-Bond Approach.

A multiple-hydrogen-bond approach was applied to shorten Pt-X-Pt distances in Cl- and Br-bridged Pt chain complexes. [Pt(dabdOH)2Cl]Cl2 (5) and [Pt(dabdOH)2Br]Br2 (6) (dabdOH = (2 S,3 S)-2,3-diaminobutane-1,4-diol) contain hydroxy groups, which form additional hydrogen bonds with counteranions. 5 has the shortest Pt-Cl-Pt distance (5.0747(8) Å) of all Cl-bridged Pt chain complexes reported to date. Furthermore, the smallest optical gap (1.45 eV for 5 and 1.19 eV for 6) in any Cl- or Br-bridged Pt chain complex was achieved. 6 has the highest electrical conductivity (1.9 × 10-5 S cm-1 at room temperature) of all Br-bridged Pt chain complexes. This study shows that the introduction of additional hydrogen bonds between the ligands and halides is effective to enhance the electronic properties of halogen-bridged metal complexes.

Randomised phase II trial of irinotecan plus S-1 in patients with gemcitabine-refractory pancreatic cancer.

BACKGROUND: We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients were treated with oral S-1 (80-120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m-2 on days 1 and 15 every 4 weeks; IRIS group) or oral S-1 group (80-120 mg daily for 28 days every 6 weeks). The primary endpoint was progression-free survival (PFS). RESULTS: Of 137 patients enrolled, 127 were eligible for efficacy. The median PFS in the IRIS group and S-1 monotherapy group were 3.5 and 1.9 months, respectively (hazard ratio (HR)=0.77; 95% confidence interval (CI), 0.53-1.11; P=0.18), while the median overall survival (OS) were 6.8 and 5.8 months, respectively (HR=0.75; 95% CI, 0.51-1.09; P=0.13). Response rate was significantly higher in the IRIS group than in the S-1 monotherapy group (18.3% vs 6.0%, P=0.03). Grade 3 or higher neutropenia and anorexia occurred more frequently in the IRIS group. CONCLUSIONS: There was a trend for better PFS and OS in the IRIS group that could be a treatment arm in the clinical trials for gemcitabine-refractory pancreatic cancer.

Diagnosis and treatment of bone metastasis: comprehensive guideline of the Japanese Society of Medical Oncology, Japanese Orthopedic Association, Japanese Urological Association, and Japanese Society for Radiation Oncology.

Diagnosis and treatment of bone metastasis requires various types of measures, specialists and caregivers. To provide better diagnosis and treatment, a multidisciplinary team approach is required. The members of this multidisciplinary team include doctors of primary cancers, radiologists, pathologists, orthopaedists, radiotherapists, clinical oncologists, palliative caregivers, rehabilitation doctors, dentists, nurses, pharmacists, physical therapists, occupational therapists, medical social workers, etc. Medical evidence was extracted from published articles describing meta-analyses or randomised controlled trials concerning patients with bone metastases mainly from 2003 to 2013, and a guideline was developed according to the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014. Multidisciplinary team meetings are helpful in diagnosis and treatment. Clinical benefits such as physical or psychological palliation obtained using the multidisciplinary team approaches are apparent. We established a guideline describing each specialty field, to improve understanding of the different fields among the specialists, who can further provide appropriate treatment, and to improve patients' outcomes.

A randomized phase II study of S-1 plus oral leucovorin versus S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer.

BACKGROUND: We evaluated the efficacy and toxicity of adding oral leucovorin (LV) to S-1 when compared with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer (PC). PATIENTS AND METHODS: Gemcitabine-refractory PC patients were randomly assigned in a 1:1 ratio to receive S-1 at 40, 50, or 60 mg according to body surface area plus LV 25 mg, both given orally twice daily for 1 week, repeated every 2 weeks (SL group), or S-1 monotherapy at the same dose as the SL group for 4 weeks, repeated every 6 weeks (S-1 group). The primary end point was progression-free survival (PFS). RESULTS: Among 142 patients enrolled, 140 were eligible for efficacy assessment (SL: n = 69 and S-1: n = 71). PFS was significantly longer in the SL group than in the S-1 group [median PFS, 3.8 versus 2.7 months; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.37-0.85; P = 0.003]). The disease control rate was significantly higher in the SL group than in the S-1 group (91% versus 72%; P = 0.004). Overall survival (OS) was similar in both groups (median OS, 6.3 versus 6.1 months; HR, 0.82; 95% CI, 0.54-1.22; P = 0.463). After adjusting for patient background factors in a multivariate analysis, OS tended to be better in the SL group (HR, 0.71; 95% CI, 0.47-1.07; P = 0.099). Both treatments were well tolerated, although gastrointestinal toxicities were slightly more severe in the SL group. CONCLUSION: The addition of LV to S-1 significantly improved PFS in patients with gemcitabine-refractory advanced PC, and a phase III trial has been initiated in a similar setting. CLINICAL TRIALS NUMBER: Japan Pharmaceutical Information Center: JapicCTI-111554.

Investigation of a high spatial resolution method based on polar coordinate maximum entropy method for analyzing electron density fluctuation data measured by laser phase contrast.

Laser phase contrast is a powerful diagnostic method to determine the spatial distribution of electron density fluctuations in magnetically confined plasmas, although its applicability depends on magnetic field configurations. The spatial resolution of fluctuations is linked with the resolution of the propagation direction that is derived from the two-dimensional spectral analysis of the wavenumber for the fluctuations. The method was applied to fluctuation measurements in a compact helical system. In order to improve the resolution of the propagation direction with a relatively small number of data points, the maximum entropy method with polar coordinates was employed. A spatial resolution of the order of 1 cm was obtained, which is satisfactory in a plasma with a 20 cm minor radius.

Comparative risk of common peroneal nerve injury in far anteromedial portal drilling and transtibial drilling in anatomical double-bundle ACL reconstruction.

PURPOSE: The purpose of this study was to investigate the risk of common peroneal nerve injury in FM drilling as compared to transtibial drilling in anatomical double-bundle ACL reconstruction. METHODS: Ten cadaveric knees without ligament injury or significant arthritis were used for this study. Knees were secured at 90° and 120° of flexion. In transtibial drilling groups, a guide pin was drilled through either the anteromedial bundle (AMB) or posterolateral bundle (PLB) tibial insertion site to either the AMB or PLB femoral insertion site (tibial insertion site-femoral insertion site: AM-AM, PL-PL, PL-AM and AM-PL). In FM drilling groups (FM-AM and FM-PL),the pin was drilled at the AMB or PLB femoral insertion site through the FM. We measured the shortest distance between the point at which the pin ran through the lateral cortex of the femur and the ipsilateral common peroneal nerve at a knee flexion of 90° and 120°. RESULTS: At a knee flexion of 90°, the shortest mean distance to the common peroneal nerve was 15.3 mm in the FM-PL group, 13.4 mm in the FM-AM group, 27.9 mm in the PL-PL group, 30.8 mm in the AM-AM group, 37.8 mm in the PL-AM group and 29.5 mm in the AM-PL group. At a knee of flexion 120°, the mean distance was 17.3 mm in the FM-PL group, 18.1 mm in the FM-AM group, 32.2 mm in the PL-PL group, 36.6 mm in the AM-AM group, 38.0 mm in the PL-AM group and 35.2 mm in the AM-PL group. Significant differences were observed between 90° and 120° of knee flexion in the FM-AM, PL-PL, AM-AM and AM-PL groups (P < 0.05). Significant differences were observed at flex 90° between the FM-AM group and AM-AM group, and between the FM-AM group and PL-AM group. Significant differences were observed at flex 120° between the FM-AM group and AM-AM group, between the FM-AM group and PL-AM group and between the FM-PL group and AM-PL group. CONCLUSION: The distance to the peroneal nerve in FM drilling was significantly longer at 120° than at 90° of knee flexion. Therefore, the risk of peroneal injury using FM drilling should decrease at a higher angle of knee flexion.

The role of immune cells in brain metastasis of lung cancer cells and neuron-tumor cell interaction.

Following any type of brain injury such as lesion, stroke, and tumor/cancer invasion, microglia are rapidly activated and recruited to the site of injury. Microglia is the main immune effector cell population of the central nervous system and control immune cell recruitment. However, the molecular mechanism of brain metastasis and interaction between neuron-glia-tumor cells are poorly understood. Therefore, we established an animal model for brain metastasis using human lung cancer-derived cells (HARA-B) in nude mice. Accumulation of activated microglia was observed around tumor cells depending on the size of metastatic foci and the area of the brain. In vitro study, conditioned medium from primary cultured mouse microglia inhibited the proliferation of tumor cells, while tumor cell-conditioned medium inhibited the proliferation of primary cultured neurons from mouse cortex. Though the responsible factors released from microglia and tumor cells are still under investigation, these studies will contribute to understand the mechanism of cell-cell interaction in the brain and possible therapeutic target for brain metastasis.

Development of a phase contrast imaging system based on a yttrium aluminum garnet laser with folded beam for observations of density fluctuations in compact helical system.

A near-infrared laser phase contrast optical system incorporating a folded beam was developed in order to measure the distribution of density fluctuations in a high-temperature plasma. The coherent light source used was an yttrium aluminum garnet laser stabilized by a ring oscillator. The probe beam system separates and reflects the incident and exiting beams with a polarizer and a fully reflective mirror with a waveplate. This system was employed with a compact helical system to detect fluctuations at the plasma edge.

Reconstruction method of local density fluctuation for heavy ion beam probe measurements.

Heavy ion beam probe (HIBP) is an excellent diagnostic to measure the density and potential fluctuations simultaneously in magnetically confined plasmas. However, it has been well known that the density fluctuation measured with the HIBP is not local but contains the fluctuations along the beam orbits. In this article, a method is proposed to evaluate local density fluctuation in the HIBP measurements by removing the well-known path integral effects. The reconstructed density fluctuation amplitude and power spectrum are shown, for example, by applying the proposed method on the density fluctuation measurement data obtained in a toroidal helical plasma, Compact Helical System.

Experimental evidence of a zonal magnetic field in a toroidal plasma.

A zonal magnetic field is found in a toroidal plasma. The magnetic field has a symmetric bandlike structure, which is uniform in the toroidal and poloidal directions and varies radially with a finite wavelength of mesoscale, which is analogous to zonal flows. A time-dependent bicoherence analysis reveals that the magnetic field should be generated by the background plasma turbulence. The discovery is classified as a new kind of phenomenon of structured magnetic field generation, giving insight into phenomena such as dipole field generation in rotational planets.

Long-lasting production of TGF-beta1 by alveolar macrophages exposed to low doses of asbestos without apoptosis.

Alveolar macrophages (AMs) exposed to asbestos are well known to produce TNF-alpha, which induces the production of TGF-beta1, leading to lung fibrogenesis. The present study examines the production of TGF-beta1 by AMs exposed to chrysotile B asbestos (CH) in vivo or in vitro and the relationship between TGF-beta1 production and apoptosis in cultures of AMs. Rats instilled with CH via the trachea showed increases in TNF-alpha, IL-1beta and IL-6 in the bronchoalveolar lavage fluid (BALF) 1 day after the instillation, followed by increases in TGF-beta1 and apoptotic cells 5 days after. The AMs from these BALFs produced a significantly increased amount of TGF-beta1 in culture compared to those from the control rats. The addition of 2.5 mug/cm2 of CH augmented the production of TGF-beta1 by the AMs from the control to the same level as produced by the AMs from the CH-treated rats. The apoptosis of AMs was not induced at 2.5 microg/cm2 of CH, but was drastically induced at over 12.5 microg/cm2. In contrast, the production of TGF-beta1 by AMs peaked at around 2.5 microg/cm2 of CH, and it lasted for 11 days. In addition, Bcl-2 and Bcl-xL increased in the AMs surviving under the exposure to CH. Taken together, these results indicate that AMs can autonomously, without other pulmonary cells, acquire the lasting ability to produce TGF-beta1 independently of apoptosis under low exposure to CH. The AMs with the lasting production of TGF-beta1 may contribute not only to lung fibrosis but also to immune suppression.

The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice.

The pathogenesis of bone metastases may require the activation of osteoclasts by tumor-secreted factors, which promote important interactions with the bone microenvironment. We utilized an intratibial model of bone metastasis with bioluminescent imaging (BLI) to measure the effect of osteoclast inhibition on the interaction of human lung cancer cells with bone, and on tumor growth. Mice were injected with luciferase-transduced tumor cells (HARA, human pulmonary squamous carcinoma) and divided into three groups: (1) untreated, (2) twice weekly treatment with the bisphosphonate zoledronic acid (ZOL), or (3) osteoprotegerin (OPG). Histomorphometry and imaging were used to evaluate tumor burden, and parameters of osteoclast activity. Mice in the treated groups had increased bone density and decreased osteoclast numbers in nontumor-bearing tibiae. There was greater than 60% reduction in mean tumor volume in both treatment groups when evaluated by histomorphometry (P = 0.06 [OPG], P = 0.07 [ZOL]). However, bioluminescent imaging failed to show a reduction in tumor burden due to wide variability in the data. Osteoclast numbers along tumor-associated bone were significantly increased compared to tumor-free bone, and were not reduced by either treatment. Plasma calcium concentration was increased in all groups. Plasma tartrate-resistant acid phosphatase 5b was reduced in both treatment groups. Plasma PTHrP was significantly increased in the untreated tumor-bearing group, but was not significantly different in the two treatment groups compared to normal mice. OPG or ZOL did not change tumor cell proliferation, but ZOL increased HARA cell apoptosis. OPG and ZOL reduced tumor growth in the tibiae of treated mice, however, PTHrP production by HARA cells may have resulted in a high concentration in the bone microenvironment, partially overriding the antiosteoclast effects of both OPG and ZOL.

Identification of zonal flows in a toroidal plasma.

This Letter presents experimental confirmation of the presence of zonal flows in magnetically confined toroidal plasma using an advanced diagnostic system--dual heavy ion beam probes. The simultaneous observation of an electric field at two distant toroidal locations (approximately 1.5 m apart) in the high temperature (approximately 1 keV) plasma provides a fluctuation spectrum of electric field (or flow), a spatiotemporal structure of the zonal flows (characteristic radial length of approximately 1.5 cm and lifetime of approximately 1.5 ms), their long-range correlation with toroidal symmetry (n=0), and the difference in the zonal flow amplitude with and without a transport barrier. These constitute essential elements of turbulence-zonal flow systems, and illustrate one of the fundamental processes of structure formation in nature.

Analysis of retrograde ejaculation using color Doppler ultrasonography before and after transurethral collagen injection.

Transurethral bladder neck collagen injection therapy was performed in a patient with retrograde ejaculation. The phenomenon of retrograde ejaculation and its correction after the therapy were clearly demonstrated by color Doppler ultrasonography. To our knowledge this is the first report showing successful observation of retrograde ejaculation using color Doppler ultrasonography.

[Report on the ECR2003 (European Congress of Radiology): comparison of apparent diffusion coefficient (ADC) between different MRI scanners].

PURPOSE: To analyze reproducibility of ADC measurements on different MRI scanners. METHODS AND MATERIALS: Diffusion-weighted imaging (DWI) of a home-made phantom (gelatine of different concentration was enclosed in case of circle pillar shape) was performed with the following protocol; spin-echo type echo planar imaging; TR=7000 msec, TE=minimal, matrix=128 x 128, FOV=220 mm, slice thickness=5mm, NEX=1, b-factor=0, 500, and 1000 sec/mm(2) on four different 1.5T MR scanners [GE Signa Horizon (two of them), GE Signa Horizon Lx, and Siemens Magnetom Symphony]. Image analysis were performed on a workstation (GE Medical Systems) or on an operators console of Symphony (for data of Symphony). We used two-point method. Regions of interest (ROIs) were set on every part of ADC map of home-made phantom and ADCs were measured. A linear approximation graphs were also made with every MRI scanner and b-factor. RESULTS: A linear approximation was performed, formulas were y=-0.08x+2.32, r(2)=0.84(Lx), y=-0.09x+2.58, r(2)=0.89(Horizon-1) y=-0.11x+2.67, r(2)=0.95(Horizon-2), y=-0.08x+2.42, r(2)=0.97(Symphony) at b-factor of 500sec/mm(2). y=-0.08x+2.33, r(2)=0.91(Lx), y=-0.09x+2.43, r(2)=0.93(Horizon-1), y=-0.08x +2.48, r(2)=0.92(Horizon-2), y=-0.07x+2.39, r(2)=0.96(Symphony) at b-factor of 1000 sec/mm(2). CONCLUSIONS: ADC values measured at two MRI scanners (same model and older than the other scanners) are higher than other scanners on b-factor=500 sec/mm(2), but at b-factor=1000 sec/mm(2), a good relationship between every scanners was obtained. This result seems to depend on generation of the MRI scanners; newly scanners have good relations b-factor 500 and 1000 sec/mm(2). Pulse sequence design may be improved and optimized in newly scanners. When ADCs were used as quantitative value, a proper b-factor must be used.