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Articles by Y Yamada
Total Records ( 6 ) for Y Yamada
  N. T Okita , Y Yamada , D Takahari , Y Hirashima , J Matsubara , K Kato , T Hamaguchi , K Shirao , Y Shimada , H Taniguchi and T. Shimoda
  Objective

Vascular endothelial growth factor (VEGF) and its receptors VEGF-R1, -R2 and -R3 play important roles in tumor angiogenesis and are associated with poor prognosis in several solid tumors. However, their functional significance remains unclarified. Here, we investigated the associations between the expression of these receptors and the clinical outcomes of colorectal cancer (CRC) patients.

Methods

An immunohistochemical approach was used to detect VEGF-R1, -R2 and -R3 expression in 91 CRC patients who underwent surgery and received chemotherapy at the National Cancer Center Hospital. Statistical analysis was performed to determine the prognostic significance of these biomarkers.

Results

Immunoreactivity for VEGF-R2 and -R3 was localized in microvessels and that for VEGF-R1 in cancer cells and stromal microvessels. VEGF-R1 staining in cancer cells (>10% staining) was found in 84 patients (92%) and in stromal vessels in 75 patients (82%). VEGF-R2 staining in tumor vessels (>10% staining) was found in 84 patients (92%), whereas VEGF-R3 staining was found in 85 patients (93%). Strong positive staining (>60% staining) of VEGF-R1 in tumor cells, and VEGF-R1, -R2 and -R3 in vessels was identified in 58 (64%), 33 (36%), 52 (57%) and 60 (66%) patients, respectively. Univariate analysis revealed that VEGF-R1 strong positive staining correlated with shorter post-operative survival in patients with Stage II/III disease (P = 0.01), but neither VEGF-R2 nor R3 expression correlated with survival.

Conclusions

VEGF-R1, -R2 and -R3 were highly expressed in CRC cells and stromal vessels. VEGF-R1 strong positive staining correlated with shorter survival after CRC surgery.

  K Yamada , N Yamamoto , Y Yamada , T Mukohara , H Minami and T. Tamura
  Objective

ABI-007 is a novel Cremophor® EL-free nanoparticle albumin-bound paclitaxel. This Phase I study was designed to evaluate tolerability and determine recommended dose for Japanese patients when ABI-007 was administered in every-3-week schedule. Pharmacokinetics of paclitaxel was also assessed.

Methods

Patients with advanced solid tumors refractory to standard therapy received a 30 min intravenous infusion of ABI-007 every 3 weeks without pre-medications at 200, 260 or 300 mg/m2, respectively. Tolerability and recommended dose were determined by the standard ‘3 + 3’ rule.

Results

No dose-limiting toxicity was observed, despite the dose escalation. In another cohort, 260 mg/m2 was re-evaluated and resulted in no dose-limiting toxicity. Grade 3 or 4 neutropenia was reported for the majority of patients (n = 8) but no incidence of febrile neutropenia. Non-hematological toxicities were generally mild except for Grade 3 sensory neuropathy (n = 3). Pharmacokinetic study demonstrated the area under the curve of paclitaxel increased with increasing the dosage, and comparable pharmacokinetic parameters to the western population. Partial response was observed in three non-small cell lung cancer patients. Two of whom had received docetaxel-containing chemotherapy prior to the study.

Conclusions

ABI-007 administered in every-3-week schedule was well tolerated up to 300 mg/m2, and recommended dose was determined at 260 mg/m2 in consideration of efficacy, toxicities and similarity of pharmacokinetic profile in western studies. Additional studies of single-agent ABI-007 as well as platinum-based combinations, particularly in patients with non-small cell lung cancer, are warranted.

  Y Fujisaka , Y Yamada , N Yamamoto , A Horiike and T. Tamura
  Objective

Temsirolimus (CCI-779) is a novel inhibitor of the mammalian target of rapamycin. This Phase 1 study was aimed at investigating the maximum-tolerated dose, toxicity, pharmacokinetics and antitumor activity in Japanese patients with advanced solid tumors.

Methods

Temsirolimus was given as a 30 min intravenous infusion once a week. Patients with solid tumors not amenable to standard forms of treatment were eligible. Dose escalation of temsirolimus was planned from 15, 45, 80 to 165 mg/m2. The pharmacokinetics of temsirolimus and sirolimus in whole blood were examined for cycles 1, 2, 4 and 5 of treatment.

Results

Ten patients (median age 60.5 years; range 41–69 years) with advanced solid tumors were enrolled. Their primary cancers were renal cell carcinoma (five patients), lung cancer (three patients) and colorectal cancer (two patients). The major toxicities were hypophosphatemia diarrhea, hyperglycemia, stomatitis, pyrexia, elevated aspartate aminotransferase, rash, reduced neutrophil count, elevated alanine aminotransferase, anorexia, hypertriglyceridemia and somnolence. Two of three patients who received temsirolimus 45 mg/m2 developed dose-limiting toxicities of Grade 3 stomatitis (one patient) and Grade 3 diarrhea (two patients). The maximum-tolerated dose was 15 mg/m2. The peak blood concentrations of temsirolimus and sirolimus, a major active metabolite, increased in a dose-dependent manner. The area under the concentration-versus-time curve of sirolimus, but not temsirolimus, increased in a dose-dependent manner.

Conclusions

The recommended dose for Phase 2 clinical studies of temsirolimus in Japanese patients with advanced solid tumors is 15 mg/m2 intravenously once a week.

  T Tsukada , H Taniguchi , S Ootaki , Y Yamada and M. Inoue
 

This study aimed to describe the electromyographic (EMG) activity patterns of the genioglossus (GG) and suprahyoid (SHy) muscles during swallowing. The effects of changes in food texture/consistency and head posture on transport of the swallowed bolus were also investigated. Participants were 10 normal adults. Test foods consisted of a liquid, a syrup, or 4 ml of paste made from 0.5% or 1.0% agar. Each food was swallowed with the head in one of three positions, and EMGs and videofluorographic (VF) images were recorded. Mean values of onset, peak, and offset times, peak amplitude, area, and duration of the EMG burst were measured. The total swallowing time, oral ejection time, pharyngeal transit time, clearance time, fauces transit time, and upper esophageal sphincter (UES) transit time were measured. The GG muscle burst patterns showed two peaks (GG1 and GG2) during each swallowing. The offset time and duration of the GG1 burst and the onset, peak, and offset times and duration of both the GG2 and SHy bursts were significantly affected by food texture. There were no significant differences in bolus transit time among the different experimental conditions. Regression analyses demonstrated significant linear relationships between the tongue tip touching the palate and the peak of the GG1 burst, between passage of the bolus tail at the fauces and offset of the GG1 burst, between passage of the bolus tail at the UES and peak of the GG2 burst, and between passage of the bolus tail at the UES and offset of the SHy burst. These results demonstrate that the duration, but not the amplitude, of tongue and suprahyoid muscle activity were increased with increasing hardness of food during swallowing and that the bolus transit time can be fixed within a certain range of physical food properties.

  K Fukutsu , Y Yamada and M. Akashi
 

A positive nasal swab taken at a radiation emergency, when properly collected and analysed, is a good indication of a potential inhalation intake. It may be expected to be a useful method for early dose assessment in cases of accidental inhalation of an alpha emitter. To improve the first estimation of intake activity, the quality of a nasal swab measurement was experimentally investigated. Alpha spectrometry was used to examine the experimental nasal swab samples involved with a plutonium solution or particles. Also, a numerical simulation analysis on the alpha spectrum using advanced alpha-spectrometric simulation was made to characterise the experimental results. It was observed that the alpha energy spectrum had a quite different shape among samples, and it was characterised by the type of contaminant. This could be the second advantage of using alpha spectrometry in addition to nuclide identification. The absorption of alpha radiation within the experimental nasal swab sample was different between the types of contaminants. For a quantitative discussion, the absorption for a swab sample must be determined for each type of contaminant. This new finding could be very useful for first responders. A nasal swab sample measured using an alpha spectrometer will give more useful information during the first response of an emergency.

  Y Yamada , K Fukutsu , M Yuuki and M. Akashi
 

After radiological emergencies, patients contaminated with radioactivity are taken to radiation emergency hospitals for treatment. Numerical simulations using the computer software ‘Flow Designer®’ were made in order to evaluate indoor air contamination caused by the breathing out of contaminated air. The National Institute of Radiological Sciences facility was used for the numerical evaluation. Results indicate that the dispersion of contaminated air depends on the characteristics of the contaminants, and that the dispersion range was limited and localised. Only medical staff standing in a special position near the patient was exposed to almost un-diluted contaminated air. Highly contaminated air was evacuated with a local exhaust pump system. Room air quality was monitored using a continuous air sampling system, but it was found that the sampling point was not representative for the purpose of radiation protection. From the air-flow analysis, some problems that affect radiological safety were revealed and valuable information and measures for preventing secondary contamination were determined.

 
 
 
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