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Takashi Yoshioka

Publications and source records attributed to Takashi Yoshioka.

At least 19 recordsLinked to original sources
PubMed2006

Dose escalation study of docetaxel and nedaplatin in patients with relapsed or refractory squamous cell carcinoma of the esophagus pretreated using cisplatin, 5-fluorouracil, and radiation.

BACKGROUND: Definitive chemoradiation with cisplatin (CDDP) and 5-fluorouracil (5FU) has been playing an important role in the treatment of esophageal cancer, but some patients are not curable or have recurrent lesions. However, few chemotherapeutic regimens are available for such patients. Docetaxel and nedaplatin are active for esophageal cancer. We conducted a dose-escalation study of docetaxel and nedaplatin as second line-chemotherapy after definitive chemoradiation in patients with relapsed or refractory squamous cell carcinoma of the esophagus after chemoradiation. METHODS: Nedaplatin was administered on day 1 and docetaxel was administered on days 1 and 15, every 4 weeks. Dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle. RESULTS: Twelve patients were enrolled. At a docetaxel dose of 30 mg/m(2) and a nedaplatin dose of 80 mg/m(2), one grade 4 neutropenia occurred and caused one treatment break longer than 2 weeks, but there were few DLTs. At doses of 35 and 80 mg/m(2), respectively, two grade 4 neutropenias and one grade 2 thrombopenia occurred and caused three treatment breaks longer than 2 weeks. Therefore, the maximum tolerated dose was established at this dose level. Two grade 3 anorexias and one grade 3 nausea occurred, but other non-hematological toxicities were generally mild. Responses were seen in one-fourth of the 12 patients, including one complete remission. CONCLUSION: The recommended doses of docetaxel and nedaplatin were 30 and 80 mg/m(2), respectively. This combination could be a potential second-line treatment for this target population.

Aged↗
PubMed2006

O-[18F]fluoromethyl-L-tyrosine is a potential tracer for monitoring tumour response to chemotherapy using PET: an initial comparative in vivo study with deoxyglucose and thymidine.

PURPOSE: To compare the utility of a new artificial amino acid, O-[18F]fluoromethyl-L-tyrosine ([18F]FMT), for monitoring cancer chemotherapy with deoxyglucose and thymidine. METHODS: [18F]FMT, [14C]deoxyglucose ([14C]DG) and [6-3H]thymidine ([3H]Thd) were applied in this study. A 2.5 mg/kg dose of mitomycin (MMC) was administered to AH272 rat hepatoma-bearing Donryu rats. Tumour uptake of each tracer was measured just before (baseline) and on days 1, 3, 5 and 7 after the MMC administration, 1 h after a mixture of [18F]FMT, [14C]DG and [3H]Thd had been injected, and was shown as DURs (% injected dose/gram tissue normalised for the rat body weight). Dual-tracer macroautoradiographs with [18F]FMT and [14C]DG were also prepared. RESULTS: The tumour uptake for each tracer decreased earlier than did the tumour size. DURs (mean+/-SD) at baseline and on days 1, 3, 5 and 7 were as follows: [18F]FMT: 4.68+/-0.72, 3.34+/-0.66, 3.13+/-0.72, 3.42+/-0.45, 3.01+/-0.32; [14C]DG: 3.26+/-0.40, 3.09+/-0.55, 3.01+/-0.97, 2.28+/-0.35, 1.70+/-0.72; and [3H]Thd: 2.23+/-0.46, 1.54+/-0.45, 1.28+/-0.37, 1.35+/-0.20, 0.94+/-0.12. Decrease in [18F]FMT uptake compared with baseline was significant from day 1 (p<0.01), and the decrease in [3H]Thd uptake was also significant on day 1 (p<0.05) and days 3-7 (p<0.01). However, decrease in [14C]DG uptake was only significant from day 5 (p<0.01). Macroautoradiography suggested that the influence of inflammatory cells on the accumulation of [18F]FMT in tumours is smaller than that on the accumulation of [14C]DG. CONCLUSION: [18F]FMT uptake shows a rapid and sensitive response to chemotherapy, comparable to that of [3H]Thd, suggesting that it may be applied as a powerful tracer for monitoring of proliferative activity after cancer chemotherapy using PET.

Animals↗
PubMed2006

Influence of disease stage on polyethylenimine-mediated plasmid DNA delivery in murine hepatitis.

In order to determine the influence of hepatic disease-stage on polyethylenimine-mediated gene delivery, we investigated branched and linear polyethylenimine (B-PEI, L-PEI)-mediated plasmid DNA delivery with time in murine hepatitis induced by a subcutaneous injection of tetrachloro carbon (CCl(4)). Plasmid DNA (pDNA) encoding firefly luciferase was used as the model reporter gene. We determined luciferase activity in various organs of CCl(4)-treated mice and control mice after an intravenous administration of B-PEI and L-PEI/pDNA complexes. Both B-PEI and L-PEI/pDNA complexes showed significantly lower gene expression in the liver, spleen, and lung at the stage of severe hepatitis (18 h after CCl(4) injection), whereas the complexes induced gene expression in the liver at the liver regeneration stage (48 h after CCl(4) injection). Significant differences in gene expressions between CCl(4)-treated mice and control mice vanished in most organs at the hepatitis subsidence stage (168 h after CCl(4) injection), indicating that the influence of hepatitis induced by CCl(4) was reversible with PEI-mediated gene delivery. Our findings demonstrated that murine hepatitis induced by CCl(4) could influence polyethylenimine-mediated plasmid DNA delivery according to the disease stage. These results indicate the necessity of considering the timing and dose of gene therapy according to the disease stage.

Animals↗
PubMed2006

Spatiotemporal receptive fields of peripheral afferents and cortical area 3b and 1 neurons in the primate somatosensory system.

Neurons in area 3b have been previously characterized using linear spatial receptive fields with spatially separated excitatory and inhibitory regions. Here, we expand on this work by examining the relationship between excitation and inhibition along both spatial and temporal dimensions and comparing these properties across anatomical areas. To that end, we characterized the spatiotemporal receptive fields (STRFs) of 32 slowly adapting type 1 (SA1) and 21 rapidly adapting peripheral afferents and of 138 neurons in cortical areas 3b and 1 using identical random probe stimuli. STRFs of peripheral afferents consist of a rapidly appearing excitatory region followed by an in-field (replacing) inhibitory region. STRFs of SA1 afferents also exhibit flanking (surround) inhibition that can be attributed to skin mechanics. Cortical STRFs had longer time courses and greater inhibition compared with peripheral afferent STRFs, with less replacing inhibition in area 1 neurons compared with area 3b neurons. The greater inhibition observed in cortical STRFs point to the existence of underlying intracortical mechanisms. In addition, the shapes of excitatory and inhibitory lobes of both peripheral and cortical STRFs remained mostly stable over time, suggesting that their feature selectivity remains constant throughout the time course of the neural response. Finally, the gradual increase in the proportion of surround inhibition from the periphery to area 3b to area 1, and the concomitant decrease in response linearity of these neurons indicate the emergence of increasingly feature-specific response properties along the somatosensory pathway.

Afferent Pathways↗
PubMed2006

Phase I-II study of biweekly paclitaxel administration with fixed-dose-rate cisplatin in advanced gastric cancer.

BACKGROUND: Both paclitaxel (TXL) and cisplatin (CDDP) show efficacy against gastric cancer. The aim of this phase I-II study was to determine the maximum tolerated dose (MTD) and to evaluate the toxicity and efficacy of combination chemotherapy with these two agents. METHODS: Nineteen patients entered the phase I part of the study, and 21 patients entered the phase II part. TXL infusions were administered on days 1 and 15, with a fixed 3mg/m2 dose of CDDP. RESULTS: In the phase I part of the study, we determined dose level 5, which represented a TXL dose of 18 mg/m2, with CDDP 3 mg/m2, to be the MTD. The recommended dose (RD) was level 4, with a TXL dose of 16 mg/m2 with CDDP, 3 mg/m2. In the phase II part of the study, the response rate was 25.0%; five patients had a partial response, seven had stable disease, 6 had progressive disease, and 2 were not evaluable. Grade 3 or 4 neutropenia was the most common adverse event and occurred in 65% of the patients. During treatment, 25% of the patients received granulocyte colony-stimulating factor, but febrile neutropenia was not shown in any of the patients. Major nonhematological toxicities were nausea/vomiting, anorexia, fatigue, alopecia, and sensory neuropathy. Adverse reactions of grade 3 or 4 were shown by two patients, one with anorexia (5%) and the other with sensory neuropathy (5%). CONCLUSION: The RD was determined to be TXL 14 mg/m2, with CDDP 3 mg/m2.

Aged↗
PubMed2006

Partial hepatectomy enhances polyethylenimine-mediated plasmid DNA delivery.

Polyethylenimine (PEI) is widely used for non-viral transfection in vitro and in vivo. Hepatectomy is an interesting and considerable factor modifying PEI-mediated gene expression. We investigated the gene expression in mice over time following partial hepatectomy after an intravenous injection of PEI/plasmid DNA (pDNA) complex. pDNA encoding firefly luciferase was used as the model reporter gene. The hepatectomized liver was rapidly regenerated until 72 h. After 168 h, the liver weight of hepatectomized mice was similar to that of control mice. Slight liver function impairment was only observed at 1-24 h after hepatectomy in alanine aminotransferase and aspartate aminotransferase levels. Luciferase activity in the liver of partial hepatectomized mice at 48 h after partial hepatectomy increased by 70 times compared with that of control mice; however, luciferase activities did not significantly differ between hepatectomized mice and control mice in the spleen, lung, kidney, and heart. Among the lobes, luciferase activity by gram of tissue was not significantly different, indicating that gene expression enhancement by partial hepatectomy occurred equally throughout the liver. In conclusion, our findings demonstrate that liver resection is an influencing factor on PEI-mediated gene delivery in mice. These results indicate the necessity of considering cell division in PEI-mediated pDNA delivery.

Animals↗
PubMed2006

[A case of malignant melanoma from the esophagus responding to weekly paclitaxel therapy].

A 44-year-old man had a tumor in the lower thoracic esophagus at a health check, and was initially diagnosed as an undifferentiated carcinoma of the esophagus by the esophago-gastric endoscope. Although curative chemoradiotherapy was scheduled after the diagnosis, the interim evaluation revealed that the tumor was malignant melanoma of the esophagus with right renal metastasis. Since then, CVD (cisplatin, vindesine and dacarbazine) therapy, palliative radiotherapy and DAC-Tam (dacarbazine, nimustine, cisplatin and tamoxifen) therapy were carried out, but all of them proved ineffective, and multiple newly metastatic lesions appeared in liver and lymph nodes. Oral intake was impossible because of progressing stricture of the esophagus. As a fourth-line therapy, weekly paclitaxel therapy was started, and his oral intake was improved after the second course. He received the therapy as an outpatient for four months. After the third course, tumor lesions were evaluated as a partial response by CT. Consequently, five courses of the therapy were performed with modest adverse effects. Weekly paclitaxel therapy was reasonably safe as reported in other reports and considered to be a promising regimen for malignant melanoma of the esophagus.

Adult↗
PubMed2005

[Retrospective analysis on efficacy and toxicity of 5-fluorouracil (5-FU) and l-leucovorin (l-LV) in advanced or recurrent colorectal cancer].

The aim of this study was to evaluate the efficacy and toxicity of 5-fluorouracil (5-FU) and l-leucovorin (I-LV) in 50 patients with advanced or recurrent colorectal cancer in our institute. The dose of 5-FU was 600 mg/m2 and the dose of l-LV was 250 mg/m2. Objective response were 36.8% of patients who had administration of full-dose and 14.8% of patients who had the administration of reduced dose or prolonged interval. No significant difference was observed in clinical benefit rates between patients administrated in full-dose and patients in reduced dose or prolonged interval. Median survival time (MST) of patients in reduced dose or prolonged interval is longer than patients in full-dose. These data suggest that 5-FU/l-LV can be given in the outpatient and yields improved prognosis and minimal adverse reactions even in patients in reduced dose or prolonged interval.

Adult↗
PubMed2004

The RING finger protein, RNF8, interacts with retinoid X receptor alpha and enhances its transcription-stimulating activity.

Retinoid X receptor alpha (RXR alpha) is a member of the steroid hormone receptor superfamily. Using yeast two-hybrid screening, beta-galactosidase assays, and pull-down assays, we show that RNF8, a RING finger protein recently isolated as a protein binding to a ubiquitin-conjugating enzyme, binds to RXR alpha through the N-terminal regions of both proteins. In COS7 cells, overexpressed RNF8 colocalized and interacted with RXR alpha in the nucleus, as shown by fluorescence resonance energy transfer. A point mutation of RNF8, Cys-403 to Ser (C403S), which disrupts the RING finger structure, or deletion of the N-terminal region (Delta N) of RNF8 prevented localization of RNF8 to the nucleus without affecting nuclear localization of RXR alpha. Although transient overexpression of RNF8 had little effect on RXR alpha ubiquitination, RNF8 dose-dependently enhanced RXR alpha-mediated transactivation of the RXR-responsive element (RXRE)-bearing gene promoter without the addition of its ligand, 9-cis-retinoic acid (RA), and up-regulated the expression of the genes downstream of RXRE as well as an RA-response element. This transactivation-enhancing activity was not seen with either the C403S point mutant or the Delta N deletion mutant of RNF8. These results suggest a novel function of RNF8 as a regulator of RXR alpha-mediated transcriptional activity through interaction between their respective N-terminal regions.

Animals↗
PubMed2004

A novel germline mutation of the LKB1 gene in a patient with Peutz-Jeghers syndrome with early-onset gastric cancer.

The gene responsible for Peutz-Jeghers syndrome (PJS), LKB1 (also called STK11) was mapped to chromosome 19p13.3 and was found to encode a putative serine/threonine protein kinase, LKB1. As only a limited number (approximately 100) of germline mutations of the gene have been reported, and because the protein function is still unclear, information about LKB1 mutations and their expression should be accumulated to understand the phenotype-genotype correlation of this disease. Here we report a patient with sporadic PJS with early-onset gastric cancer. We found a novel germline frameshift mutation (757-758insT) in the LKB1 gene and a marked reduction in LKB1 protein expression in the carcinoma cells, suggesting that the loss of LKB1 function may have led to the carcinogenesis of the gastric cancer.

AMP-Activated Protein Kinase Kinases↗
PubMed2004

Neuronal protein NP25 interacts with F-actin.

Neuronal protein NP25 is a neuron-specific protein present in highly differentiated neural cells, but its functional properties have not been well characterized. NP25 shows high amino acid sequence homology with the smooth muscle cell cytoskeleton-associated proteins, SM22, mp20, and calponin. To gain an insight into the biological functions of NP25, we first examined its subcellular localization in the human neuroblastoma cell line, SK-N-SH. NP25 diffusely distributed in the cytoplasm and fiber-like staining was also observed. It showed that NP25 co-localized with F-actin on stress fibers. A co-sedimentation assay demonstrated that NP25 bound to filamentous actin. Further investigations using fluorescence resonance energy transfer (FRET) technique revealed intracellular binding of NP25 and actin. The significance of the interaction between NP25 and F-actin is discussed.

Actins↗
PubMed2004

Hepatitis C virus decreases in patients with maintenance hemofiltration therapy.

Low incidence rates of hepatocellular carcinoma and cirrhosis in HCV-antibody-positive patients on chronic hemodialysis are reported. Among the patients, two cases undergoing negative conversion of the anti-HCV-antibody were found. Considering the size of the virus particles and the pore size of the dialysis membrane, it seems the virus does not escape from the membrane pore. Indeed, virus particles may be trapped and destroyed at the membrane surface. The size of HCV-RNA titers in HCV-antibody-positive patients receiving various kinds of chronic blood purification procedures are of interest. The subjects included 15 hemodialysis patients, 10 hemofiltration patients, 9 continuous ambulatory peritoneal dialysis patients, 7 chronic renal failure predialysis patients, and 14 patients with excellent renal function. The concentration of HCV-RNA particles in patients receiving chronic hemofiltration was significantly lower than that in patients of other groups. Hemofiltration, which is routinely performed at over 150 mm Hg TMP, may be an important key to decreasing HCV-RNA particles by a mechanism such as destruction.

Adult↗
PubMed2003

Expression of mitotic Aurora/Ipl1p-related kinases in renal cell carcinomas: an immunohistochemical study.

The Aurora/Ipl1p-related kinases, AIRK1, AIRK2 and AIRK3, are members of a novel family of oncogenic serine/threonine kinases regulated by cell cycle progression and involved in chromosome segregation and cytokinesis. In this study, we examined expression of members of the AIRK family in human renal cell carcinomas. Expression of AIRK subfamilies was examined in 64 renal cell carcinomas by immunohistochemistry. Immunostaining of AIRK1, AIRK2 and AIRK3 was observed in 95%, 47% and 98% of specimens, respectively. Moreover, in specimens from the same patient, staining of AIRK2 was correlated with proliferating cell nuclear antigen labeling. Here we provide the first description of AIRK isozyme immunostaining in human renal cell carcinoma. Although the precise physiological functions of these kinases are not known, AIRK subfamily expression may play a role in renal cell carcinoma tumorigenesis.

Aurora Kinase A↗
PubMed2003

Biweekly administration regimen of docetaxel combined with CPT-11 in patients with inoperable or recurrent gastric cancer.

BACKGROUND: Both docetaxel (TXT) and irinotecan (CPT-11) are active chemotherapeutic agents for gastric cancer. We designed a biweekly administration regimen of TXT combined with CPT-11 for 4 weeks as one cycle in patients with inoperable or recurrent gastric cancer, and conducted a dose-escalation study. METHODS: Patients with histologically confirmed gastric cancer were treated with the regimen. The dosage levels of TXT and CPT-11 were as follows: level 1, 30 mg/m(2) and 50 mg/m(2); level 2, 35 and 50 mg/m(2); level 3, 40 and 50 mg/m(2); level 4, 40 and 60 mg/m(2); and level 5, 50 and 60 mg/m(2). The dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle. RESULTS: Grade 4 neutropenia was observed at level 3, but no other DLT was observed at less than level 4 during the first cycle. However, three patients at level 3 could not continue treatment without a decrease in the dosage after the second cycle. Based on these results, level 2 was considered to be the clinically recommended dosages. CONCLUSION: Biweekly TXT and CPT-11 was well tolerated. The recommended dosages of TXT and CPT-11 for a phase II trial are 35 mg/m(2) and 50 mg/m(2), respectively.

Adult↗
PubMed2003

A Phase II study of irinotecan in combination with 120-h infusion of 5-fluorouracil in patients with metastatic colorectal carcinoma: Japan Clinical Oncology Group Study (JCOG9703).

PURPOSE: To evaluate the antitumor effect and feasibility of a combination of irinotecan (CPT-11) and 5-day infusional 5-fluorouracil (5-FU) in a sequential schedule based on our previous combination phase I studies in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Forty chemotherapy-naive patients with metastatic colorectal cancer received 90-min infusion of CPT-11 at a dose of 150 mg/m(2) on days 1 and 15 and 120-h protracted infusion of 5-FU at 600 mg/m(2)/day on days 3-7, which were repeated every 4 weeks. RESULTS: The median number of actually administered courses was five, ranging from one to 14. There were 16 (40%) patients who developed grade 3 or 4 neutropenia. Grade 3 or 4 nausea/vomiting and diarrhea were seen in three (8%) and seven (18%) patients, respectively. Only one early death not related to treatment occurred during the study. There was one complete response and 17 partial responses with a response rate of 45% (95% confidence interval: 29.3-61.5%). With a median follow-up period of 22.5 months for survivors, the median survival and median progression-free survival times were 15.9 and 7.0 months, respectively. CONCLUSIONS: Although the toxicities were modest, this sequentially combined regimen is active and feasible in patients with metastatic colorectal cancer.

Adult↗
PubMed2003

Evaluation of 18F-FDG PET in patients with advanced, metastatic, or recurrent gastric cancer.

UNLABELLED: PET with 18F-FDG has been widely used in oncology, but its application for stomach neoplasms has been limited. The aim of this study was to evaluate the visual diagnostic accuracy of (18)F-FDG PET for advanced, metastatic, or recurrent gastric cancer and to generate semiquantitative values for lesions. METHODS: 18F-FDG PET scans were obtained on 42 patients (29 men, 13 women; age, 27-78 y; median age, 63 y): 20 patients with a PT931/04 scanner and 22 patients with a SET2400W scanner. The PT931/04 has a spatial resolution of 6.0 mm at full width at half maximum (FWHM) and covers 15 cm above and below the targeted lesion, and the SET2400W has a spatial resolution of 3.9 mm at FWHM and images the entire body. All PET images were interpreted visually, and tracer uptakes were quantitated as standardized uptake values (SUVs) on SET2400W images. RESULTS: The sensitivity, specificity, and accuracy as a whole were as follows: 71%, 74%, and 73%, respectively, with the SET2400W scanner and 47%, 79%, and 62%, respectively, with the PT931/04 scanner. Values were high for primary lesions, liver, lymph node, and lung metastases, but were low for bone metastases, ascites, peritonitis, and pleuritis carcinomatoses. SUVs were 8.9 +/- 4.2 (primary lesions, 19 patients/19 lesions), 6.5 +/- 2.2 (liver, 9/55), 6.1 +/- 2.5 (lymph nodes, 14/38), 6.5 +/- 1.8 (abdominal wall, 4/7), 3.9 +/- 2.0 (bone, 3/27), and 4.7 +/- 2.6 (lung, 2/3). Comparing SUVs and histologic findings for 17 untreated patients, values for well-differentiated and moderately differentiated adenocarcinomas versus poorly differentiated adenocarcinomas and signet ring cell carcinomas were 13.2 +/- 6.3 (4/4) versus 7.7 +/- 2.6 (13/13) (P < 0.05) for the primary lesions, 7.0 +/- 2.4 (5/39) versus 5.6 +/- 2.8 (2/2) for the liver, and 5.5 +/- 1.9 (9/28) versus 8.8 +/- 3.3 (3/8) (P < 0.05) for the lymph nodes. CONCLUSION: Our results indicate that 18F-FDG PET is a useful diagnostic modality for advanced, metastatic, or recurrent gastric cancer but not for detecting bone metastases, peritonitis, or pleuritis carcinomatoses. 18F-FDG uptake by gastric cancers is relatively high but does not parallel histopathologic features of malignancy.

Adult↗
PubMed2002

Neural coding and the basic law of psychophysics.

There have been three main ideas about the basic law of psychophysics. In 1860, Fechner used Weber's law to infer that the subjective sense of intensity is related to the physical intensity of a stimulus by a logarithmic function (the Weber-Fechner law). A hundred years later, Stevens refuted Fechner's law by showing that direct reports of subjective intensity are related to the physical intensity of stimuli by a power law. MacKay soon showed, however, that the logarithmic and power laws are indistinguishable without examining the underlying neural mechanisms. Mountcastle and his colleagues did so, and, on the basis of transducer functions obeying power laws, inferred that subjective intensity must be related linearly to the neural coding measure on which it is based. In this review, we discuss these issues and we review a series of studies aimed at the neural mechanisms of a very complex form of subjective experience-the experience of roughness produced by a textured surface. The results, which are independent of any assumptions about the form of the psychophysical law, support the idea that the basic law of psychophysics is linearity between subjective experience and the neural activity on which it is based.

Animals↗