Pladienolide is active on gastric cancer

The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6–4.0) and 1.2 ± 1.1 (range, 0.4–3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens\u27 antibacterial susceptibility

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010.The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents.Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S.aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S.pneumoniae were 1.1% and 0.0%, respectively. Among H.influenzae, 17.6% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be β-lactamase-non-producing ABPC-resistant and 11.0% to be β-lactamase-producing ABPC-resistant strains. Extended spectrum β-lactamase-producing K.pneumoniae and multi-drug resistant P.aeruginosa with metallo β-lactamase were 2.9% and 0.6%, respectively.Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis

Fluorometric determination of ammonia in river water by flow injection analysis

Flow injection analysis(FIA) was examined for the fluorometric determination of ammonia in river water. Ammonia reacted with ο-phthalaldehyde(OPA) in the presence of 2-mercaptoethanol(ME) to form a fluorescent substance at pH 9.5. The reagent solution containing 10(-2) M OPA and 10(-3) M ME and the carrier fluid(distilled water) were propelled by a double plunger pump at a rate of 1.2 ml/min. The 40μl sample solution, injected into the carrier stream, was mixed with the reagent solution in a Teflon tubing (3 m, 0.5 mm i.d.) and led to a flow cell(18 μl). Fluorescence excited at λ(ex)=350 nm was measured at λ(em)=486 nm. Ions present commonly in river waters did not interfere with the determination of ammonia. An anion exchange column installed just behind a sample injection valve in the flow system was effective in eliminating interferences with amino acids. Using the proposed FIA system, trace amounts of ammonia(3150 ppb as nitrogen) in river water were determined in the rate of 40 samples per h

Continuous flow method for the determination of phosphorus using the fluorescence quenching of Rhodamine 6 G with molybdophosphate

Continuous flow method was examined for the determination of phosphorus. The molybdophosphate formed between orthophosphate and molybdate in hydrochloric acid medium diminished the fluorescence of Rhodamine 6 G. Carrier solution (distilled water) and reagent solution were propelled by double plunger pump P(1) and P(2) (flow rate : 0.98 ml/min), and sample solution(160μl) was injected into the carrier stream. The two streams were mixed in 20 cm long Teflon tubing (1 mm i.d.), and the mixture was flowed through a flow cell(18μl), at which the fluoresence of Rhodamine 6 G was detected(λ(ex) =350 nm, λ(em)=580 nm). The reagent solution consists of 0.035 M molybdenum and 1×10(-5) M Rhodamine 6 G in 0.8 M hydrochloric acid. Co-existing ions generally existing in river and sea waters did not interfere the determination of phosphorus. The calibration curve was linear from 0 to 45 ppb of phosphorus. The method was applied to sea water. The sampling rate was 20 samples per hour

Ultra-Trace Determination of Phosphate Ion Based on Filtration-Dissolution and Flow-through Spectrophotometric Measurement

A sensitive spectrophotometric method for the determination of ultra-trace amounts of phosphate ion is proposed. The colored ion associate formed between molybdophosphate and Malachite Green (MG) was filtered through a tiny membrane filter (cellulose nitrate; poresize, 1.0μm; 9mm diameter), dissolved together with the membrane filter in 1cm(3) or less of Methyl Cellosolve; the absorbance of the solution was then measured at 627nm with a flow-through system equipped with an autosampler. The absorbance, the standard deviation and the relative standard deviation of the reagent blank were 0.0270, 0.0005 and 1.8%, respectively. A calibration graph was linear over the range from 0.018 to 1.0ng cm(-3) (1ppb) of phosphorus using 40cm(3) of sample solutions; the detection limit corresponding to two-times the standard deviation of the reagent blank was 3ppt of phosphorus. By using the proposed method, phosphate ion in pure water samples were determined

Clonal Dissemination of Macrolide-Resistant and Penicillin-Susceptible Serotype 3 and Penicillin-Resistant Taiwan 19F-14 and 23F-15 Streptococcus pneumoniae Isolates in Japan: a Pilot Surveillance Study

Large-scale surveillance studies using molecular techniques such as pulsed-field gel electrophoresis (PFGE) have revealed that the spread of antibiotic-resistant pneumococci is due to clonal spread. However, in Japan, surveillance studies using such molecular techniques have never been done. Therefore, we conducted a pilot surveillance study to elucidate the present situation in Japan. Among the 145 isolates examined, the most prevalent serotype was type 19F (20%), for which most isolates were not susceptible to penicillin (86.2%) but were positive for the mef(A)/mef(E) gene (89.7%). The secondmost prevalent was serotype 3 (16.6%), for which most isolates were susceptible to penicillin (87.5%) and positive for the erm(B) gene (91.7%). PFGE analysis showed that both serotypes consisted mainly of clonally identical or related isolates and, in particular, 38% of the type 19F isolates were indistinguishable from or closely related to the Taiwan 19F-14 clone. In addition, some of the Japanese type 23F isolates with the erm(B) gene were indistinguishable from or related to the Taiwan 23F-15 clone as analyzed by PFGE. Based on the results of our pilot study performed in a single institution, it is likely that international antibiotic-resistant clones have already spread in Japan; therefore, a nationwide surveillance study should be urgently conducted

A preliminary study on rectal dose reduction associated with hyaluronic acid implantation in brachytherapy for prostate cancer

Objectives: Hydrogel spacer (HS) was developed to reduce rectal toxicities caused by radiotherapy, but has been reported to cause major adverse events. Our institute has attempted to introduce a hyaluronic acid (HA) as an alternative spacer. This study aimed to compare rectal doses and geometric distributions between the HS and HA implantation in prostate cancer. Methods: HS and HA were inserted in 20 and 18 patients undergoing high-dose brachytherapy, respectively. The rectum spacer volumes injected were 10 mL and 22 mL, respectively. In the treatment planning system, 13.5 Gy was administered with common catheter positions. The rectal dose indices were assessed between the spacer groups for dosimetry evaluation. Distances between the prostate and rectum and configurations of the spacers were compared. Results: The mean doses irradiated to 0.1 and 2 mL of the rectum were 10.45 Gy and 6.71 Gy for HS, and 6.73 Gy and 4.90 Gy for HA (p<0.001). The mean minimum distances between the prostate and rectum were 1.23 cm and 1.79 cm for HS and HA, respectively (p<0.05). Geometrical configuration comparisons revealed that HA has a higher ability to expand the space than HS. Conclusion: The rectal dose reduction ability of HA is significantly greater than that of HS, suggesting its potential as a new spacer

Sensitive determination of ammonia in exhaust gas of thermal power plant using gas permeation/flow injection system

A flow injection analysis coupled with a gas permeation unit for the sensitive determination of ammonia was investigated to improve the sensitivity and the rapidity of the determination of trace amounts of ammonia in exhaust gas. As gas sampling times are shortened, ammonium concentrations in absorption liquid (boric acid solution) will be lowered; the determination sensitivity of ammonia in the absorption liquid needs to be improved. Various experimental conditions, such as reagent solutions, sample sizes, reaction temperatures, flow rates of the reagent solutions and the length of gas permeation tube, were investigated and optimized. Of these, the reaction temperature and the length of gas permeation tube were found to greatly effect the sensitivity improvement for the determination of ammonia. The effect of the length of the microporous PTFE tube used for the gas permeation system was investigated by varying the length from 5 cm to 50 cm. The results showed that is the 50 cm tube, the peak height was about 6 times higher than in the 10 cm tube, and the percentage of the permeation of ammonia was about 55% and 9% in the 50 cm and 10 cm tube, respectively. Under the optimized conditions, the limit of detection of ammonia was lowered down to on fifth of the previous system. The limit of detection corresponding to the standard deviation of the reagent blank of 3 was 4 μg l(-1) of NH(4)(+). A calibration graph was linear from 10 μg l(-1) to 500 μg l(-1) of NH(4)(+). The relative standard deviations for 50 μg l(-1) and 100 μg l(-1) of NH(4)(+) were 4.5% and 2.3%, respectively. The proposed method was suitably applied to the determination of ammonia in the exhaust gas of the thermal power plant