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Biomedical subjects

Tsuyoshi Miura

Publications and source records attributed to Tsuyoshi Miura.

13 recordsLinked to original sources
PubMed2006

[The relationship between plasma level of VEGF or soluble Flt-1 and efficacy of hepatic arterial chemotherapy in patients with liver metastasis of colorectal cancer].

PURPOSE: To clarify the clinical significance of determining plasma levels of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in colorectal cancer, changes in plasma levels of VEGF and sFIt 1 during hepatic arterial chemotherapy were investigated in patients with liver metastases of colorectal cancer. PATIENTS AND METHODS: The relationship between plasma level of VEGF or sFlt-1 and serum level of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), or the efficacy of hepatic arterial chemotherapy was investigated in patients with liver metastases of colorectal cancer (n=19). Plasma levels of VEGF and sFlt-1 were determined by the enzyme linked immunosorbent assay. RESULTS: There was a positive relationship between plasma level of sFlt-1 and serum level of CEA (p = 0.13). The other combinations did not show any statistical correlations. Also, in terms of the doubling time (DT), there was a positive relationship between the sFlt1-DT and the CEA-DT (p = 0.04). The levels of VEGF tended to change in accordance with the efficacy of chemotherapy. In contrast, plasma levels of sFlt-1 increased in patients with the progressive disease, whereas the levels did not decrease in patients with the partial response. CONCLUSIONS: These results suggested that (1) VEGF may be a useful tumor marker during the chemotherapy in patients, whose CEA and CA19-9 are below the cutoff, and (2) the shrinkage of liver metastases may not cause a decrease in sFlt-1 or the half-life of sFlt-1 may be considerably long.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Effects of disialoganglioside GD3 on the mitochondrial membrane potential.

GD3 is an intracellular mediator of apoptotic signaling. Although GD3 is known to directly act on mitochondria, the dynamic responses of individual mitochondria to GD3 remain to be elucidated. In the current study, the membrane potential of single mitochondria is observed in the presence of GD3 or its analogues. Here, we report that (1) GD3 specifically induces gradual depolarizations of the inner membrane by a mechanism that differs from the permeability transition, and (2) the GD3-induced depolarizations are suppressed by cyclosporin A. These results suggest that GD3 depolarizes mitochondria by a mechanism distinct from but relevant to the permeability transition.

Animals↗
PubMed2005

[Intra-arterial infusion chemotherapy for advanced cancer--40 years of experience].

During the period of 1990-2005, 701 patients with the hepatocellular carcinoma were treated with intra-arterial infusion of 5-FU and epi-adriamycin with or without Lipiodol chemoembolization employing an implantable infusion port system. In 70% of the patients treated, an objective response was observed with marked regression of tumor and decrease in tumor marker (AFP and PIVKA-II). Also 1,091 patients with the metastatic liver cancer of colon, rectum, stomach and pancreas were treated with the same procedure employing 5-FU, mitomycin C, adriamycin, or epi-adriamycin. In more than 80% of the patients treated, an objective response was observed with marked regression of tumor and decrease in tumor marker (CEA, CA19-9, TPA, DUPAN-2, SPan-1). Intra-arterial infusion chemotherapy employing an implantable port system also proved to be a promising treatment modality for most of the intractable head and neck cancer, breast cancer and a few of the pancreas cancer.

Antineoplastic Agents↗
PubMed2004

Rapid oligosaccharide synthesis using a fluorous protective group.

The Bfp-OH, a novel fluorous protecting reagent, was able to be easily prepared. The Bfp group was readily introduced to a carbohydrate, removed in high yield, and recyclable after cleavage. The use of the Bfp group made it possible to synthesize a pentasaccharide by minimal column chromatography purification. Each synthetic intermediate was able to be easily purified only by simple fluorous-organic solvent extraction and monitored by TLC, NMR, and MS.

Catalysis↗
PubMed2004

[Histological examination of the effect of hepatic arterial infusion of degradable starch microspheres mixed with adriamycin and mitomycin C for liver metastases of colorectal cancer--second report].

We histologically examined the effect of hepatic arterial infusion of degradable starch microspheres mixed with adriamycin and mitomycin C (DSM therapy) for liver metastases of colorectal cancer. The subjects were 15 liver metastatic lesions from 9 patients with colorectal cancer who underwent potentially curative hepatectomy after DSM therapy. Ages were ranged from 36 to 71 years old (mean, 57). The ratio of male to female was 4 to 5. Six patients had synchronous lesion(s). A single injection dosage of the DSM therapy was comprised of 300-600 mg degradable starch microspheres, 30 mg ADM, and 10 mg MMC. Three lesions from the two patients who were given a single DSM therapy did not show any radiographical changes. In addition, histological examination of these lesions demonstrated a grade 1 effect. The radiographical effect of the 12 lesions from the 7 patients, who were given the DSM therapy at least three times, showed SD in 4 lesions, PR in 6 lesions, and PD in two lesions. Histological examination of these lesions demonstrated Grade 2 in 4 lesions and Grade 3 in 5 lesions. In conclusion, it was histologically confirmed that a repeated DSM therapy could cause satisfactory effects beyond expectations by radiographic imaging in patients with liver metastases of colorectal cancer.

Adult↗
PubMed2004

[Efficacy of hepatic arterial infusion of adriamycin and mitomycin C mixed with degradable starch microspheres for liver metastasis of colorectal cancer--correlation with the mRNA expression of DNA topoisomerase-IIalpha and glutathione-S transferase-pi in primary lesions].

DNA topoisomerase-IIalpha (topo-IIalpha) is a target enzyme of adriamycin (ADM). Glutathione-S-transferase-pi is known to be correlated with the resistance of various anticancer drugs including mitomycin C (MMC) and ADM. Expression levels of topo-IIalpha and GST-pi mRNA of primary colorectal lesions were semi-quantitatively determined by the RT-PCR method in 22 patients with colorectal cancer, who underwent hepatic arterial infusion of ADM and MMC mixed with degradable starch microspheres for synchronous (n=17) or metachronous (n=5) liver metastasis. Expression of topo-IIalpha mRNA/beta-actin mRNA was 0.872+/-0.564 (mean+/-SD) in responders (PR, n=10) and 0.369+/-0.133 in non-responders (SD+PD, n=12) (p=0.047). The relative expression of GST-pi was 0.638+/-0.593 in responders and 1.014+/-0.682 in non-responders (p=0.22). These results suggest that determining the mRNA expression of topo-IIalpha is useful for predicting the efficacy for this regimen, whereas determining the mRNA expression of GST-pi is not.

Adult↗
PubMed2003

A novel peptide synthesis using fluorous chemistry.

Three new fluorous supports for peptide synthesis, i.e., the trialkoxybenzhydryl-type (6), the Wang-type (7) and the tert-butyl-type support (8), were prepared. A bioactive peptide TRH was easily synthesized by an Fmoc strategy using the benzhydryl-type fluorous support with fluorous chemistry.

Amino Acid Sequence↗
PubMed2003

[Results of prophylactic hepatic arterial chemotherapy for liver metastases of Dukes C colorectal cancer--correlation with tumoral expression of dihydropyrimidine dehydrogenase, thymidylate synthase, p53, or orotate phosphoribosyl transferase].

The purpose of this study was (1) to disclose data from a non-randomized trial of prophylactic hepatic arterial chemotherapy for liver metastases from Dukes'C colorectal cancer, (2) to examine the influence of the expression of dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS), and p53 in the primary lesion on this chemotherapy, and (3) to examine the expression of orotate phosphoribosyl transferase (OPRT) mRNA levels in the cases of recurrence included in this study. Patients who underwent curative resection of Dukes'C colorectal cancer between November 1996 and April 2000 were examined. After curative resection, patients were non-randomly divided into two groups after obtaining their informed consent: Hepatic arterial infusion (HAI) group patients (n = 28) were given 5-FU (500 mg/body for 1 h per week, repeated 50 times) via the hepatic artery and peroral UFT-E after resection of Dukes'C colorectal cancer. Control group patients (n = 21) received UFT-E alone. Liver metastasis-free survival did not differ between the groups. Immunohistochemical examinations revealed that the expression of tumoral DPD or p53 was unlikely to affect the hepatic recurrence, although patients with a low expression of TS tended to have better survival in both groups. However, multivariate analysis by the Cox proportional hazard model revealed that a significant prognostic factor influencing the hepatic recurrence is extensive venous invasion. Expression levels of OPRT mRNA, measured in tumors of patients with recurrence (n = 6 for the HAI group; and n = 4 for the control group) were not significantly different between the groups. These results suggest that (1) intermittent hepatic arterial infusion of 5-FU in addition to oral UFT-E was not more useful than administration of UFT alone, and (2) the expression of DPD, TS, p53, and OPRT in the primary lesion was unlikely to affect the prognosis of patients included in this study.

Adult↗
PubMed2003

[Relationship between effectiveness of hepatic artery injection chemotherapy and serum VEGF].

Elevated plasma VEGF levels were reported in patients with colorectal cancer. This report presents regarding VEGF in patients who underwent hepatic artery injection chemotherapy (TAI) for liver metastasis of colorectal cancers. Thirty patients who underwent TAI for liver metastases of colorectal cancer during January 2002 to March 2003 were studied. Their serum CEA, CA19-9, and plasma VEGF were measured, and the relationships between these, their doubling times (DT) and therapeutic efficacy were examined. While the detected values and DTs were not considered significant, the tendency for DT to be the same was observed. One case with negative CEA and CA19-9 had high VEGF but negative VEGF-DT, which is compatible with therapeutic effects (PR). It appears that VEGF is a parameter that changes without direct correlation to CEA or CA19-9, and that VEGF may possibly be used as a therapeutic marker for cases with negative CEA or CA19-9.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

[Evaluation of liver metastasis of colorectal cancer following hepatic arterial infusion with degradable starch microspheres and adriamycin, mitomycin C as seen in changes in CEA at early stage of therapy].

OBJECTIVE: Recently, for the treatment of unresectable colorectal cancer with liver metastasis, hepatic artery injection of anticancer drugs suspended in degradable starch microspheres (DSM) is being performed. To predict its effectiveness, we did a retrospective study to see whether or not changes in CEA at early stages of therapy are significant. SUBJECTS AND METHOD: The subjects were 16 patients with unresectable colorectal cancer with liver metastasis (H3) who had undergone DSM therapy at least three times (mean age 65, male to female ratio of 10:6, 6 cases of synchronous metastasis and 10 cases of metachronous metastasis). Adriamycin (ADM) 30 mg and mitomycin C (MMC) 10 mg were suspended in 600 mg of DSM and injected into the common hepatic artery until embolization of the vessel was recognized (once/3-4 weeks). We examined the changes in CEA level (doubling time or half time) and the time to progression (TTP) of CEA after the third DSM treatment. RESULTS: Of the 16 patients, 4 (25%) showed rise in CEA, of which 3 died within a year. In the 12 cases with decreased CEA, the half time was 20-526 days (mean of 80 days). When the TTP of CEA was compared for the group with CEA half time less than 80 days (n = 6) to those with more then 80 days (n = 6), the TTP was significantly longer in the group with half time less than 80 days (p = 0.02 logrank test). CONCLUSION: To evaluate the effectiveness of DSM therapy, it is important to examine the changes in CEA at the early stages of treatment.

Aged↗
PubMed2002

[Audit of the safety of hepatic arterial infusion of degradable starch microspheres (DSM). Adriamycin (ADM).mitomycin C (MMC) on aged patients with liver metastases of colorectal cancer].

The purpose of this study was to clarify the safety of hepatic arterial infusion of degradable starch microspheres (DSM).adriamycin (ADM).mitomycin C (MMC) on aged patients with liver metastases of colorectal cancer. A total of 19 patients who received this therapy (DSM: 600 mg or less, ADM: 30 mg, and MMC: 10 mg) three times or more every three weeks were included. Changes in laboratory data and frequency of the occurrence of the adverse effects were compared between patients aged 75 (n = 5) or more and those aged 74 or less (n = 14). There were no significant differences in changes in the leukocyte counts, AST, ALT, and c-reactive protein levels between the groups. The frequency of adverse effects also was not different between the groups. These results suggests that this therapy is feasible with acceptable safety even in patients aged 75 years or more.

Aged↗