Shin Yoshida

Yamaguchi University, Yamaguti, Yamaguchi, Japan

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Publications (11)14.23 Total impact

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    ABSTRACT: Aim: We performed a phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer based on UDP-glucuronosyltransferase (UGT) 1A1 polymorphism. A total of 28 patients were enrolled. The dose of irinotecan was 150 mg/m(2) for patients with the *1/*1 wild-type genotype, and 70 mg/m(2) for those with the *1/*28 mutated genotype. The primary end-point was the response rate (RR); secondary end-points were safety, time to treatment failure (TTF), and overall survival (OS). In 28 patients total, genotype was wild-type in 22 and mutated in six. The RR was *1/*1 (22.7%; wild-type) vs. *1/*28 (16.7%; mutated); the median TTF was 5 months vs. 4.5 months, and the median OS was 13 months vs. 17.5 months, respectively. None of these differences were significant. Toxicities of grade 3 or higher were neutropenia (9.0% vs. 0%, respectively) and diarrhea (13.6% vs. 0%, respectively). This genotype-oriented therapy was effective and safe, and thus appears useful for patients who have complications or advanced age.
    Anticancer research 08/2013; 33(8):3423-30. · 1.71 Impact Factor
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    ABSTRACT: Hepatocellular carcinoma (HCC) often exhibits a poor prognosis due to metastatic spread caused by portal vein invasion (PVI). In the present study, we attempted to identify a novel therapeutic target related to PVI of HCC. Based on pooled genomic data, we identified RD RNA binding protein (RDBP), a member of the negative elongation factor (NELF) transcription elongation regulatory complex, to be preferentially overexpressed in HCC with PVI. We used quantitative reverse transcription polymerase chain reaction (RT-PCR) and immuno-histochemical analyses to investigate the relationship between RDBP mRNA and protein with metastatic potential in sample sets of hepatitis C virus (HCV)-related HCC and corresponding non-HCC liver tissues. We also used the small interfering RNA technique to examine the role of RDBP in invasion and proliferation of HCC cells in vitro. Our data showed that both mRNA and protein levels of RDBP were significantly higher in HCC compared to non-HCC liver tissue, and that these levels were also significantly higher in HCC with PVI compared to HCC without PVI. Multivariate analysis revealed that RDBP protein levels were an independent risk factor for early intrahepatic recurrence of HCC within 2 years of surgery. Knockdown of RDBP protein significantly inhibited the proliferation and invasion of cells in vitro. These data demonstrate that RDBP is related to the metastatic potential of HCC, suggesting a possible candidate for prevention of HCC cell metastasis.
    Oncology Reports 05/2012; 28(2):728-34. · 2.30 Impact Factor
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    ABSTRACT: It is very important for immunotherapy to release Th2-dominated and Treg-dominated immunological conditions in patients with malignant diseases. In the present study, we assessed the population of CD4+IL-10+T-cells and CD4+Foxp3+T-cells in peripheral blood in patients with colorectal cancer using a flow cytometric analysis, and we investigated whether Th2-dominated and Treg-dominated condition could be modulated by PSK. Peripheral blood samples were collected preoperatively from 40 patients with colorectal cancer before and after oral administration of PSK (3 g/day × 1 week). After PSK treatment, CD4+IL-10+T-cell percentages decreased in 63% of patients and CD4+Foxp3+T-cells percentages decreased in 63% of patients. However, no correlation was found between the ratio of CD4+IL-10+T-cell percentages and that of CD4+Foxp3+T-cell percentages after/before PSK treatment. These results suggest that PSK could release Th2-dominated and Treg-dominated immunological condition in patients with colorectal cancer. Further examinations are needed to investigate the after/before percentage ratio of CD4+Foxp3+T-cells can be useful predicting parameters for the selection of responders of PSK.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(12):2234-6.
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    ABSTRACT: The combination treatment of non-specific immunomodulator Lentinan (LNT) and OK-432 is effective for controlling Th1/Th2 balance and inducing Th1 dominant status in cancer patients. According to this rationale, we tried an administration of LNT and OK-432 in the pleural or peritoneal cavity for patients with malignant effusion. In all 21 lesions of the 20 cases, 10 revealed a complete disappearance and 7 revealed diminution of the effusion. The efficacy of this treatment is 81%. All patients developed a clinical efficacy in 1 to 3 courses of this treatment, and 9 lesions developed clinical efficacy in only 1 course. None of patients developed toxic symptoms LNT, and 10 developed a low grade fever by OK-432. The combination of LNT and OK-432 is effective and for QOL conserving loco-regional treatment.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(12):2798-800.
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    ABSTRACT: Although individuals carrying the UGT1A1 allele *28 have an increased risk of severe toxicities associated with irinotecan, no phase I study has been conducted based on the polymorphism. This report presents the recommended doses of irinotecan for patients with the respective genotypes. Twenty-seven patients with advanced colorectal cancer were enrolled in this study, and the UGT1A1*28 polymorphism was genotyped before chemotherapy. One course of chemotherapy consisted of irinotecan infused once every 2 weeks at 70, 100, 120, and 150 mg/m(2) at dose levels 1, 2, 3, and 4, respectively, and doxifluridine was administered orally. This treatment continued for at least 12 weeks. The dose-limiting toxicity was determined as grade 3 hematological and non-hematological toxicities for the TA(6)/TA(6) (6/6) and TA(6)/TA(7) (6/7) genotypes. The pharmacokinetics of irinotecan, SN-38, and SN-38 glucuronide, was assessed at dose level 2. Eighteen and nine patients had the 6/6 and 6/7 genotypes, respectively. The maximum tolerated dose (MTD) was not observed up to dose level 4 in patients with the 6/6 genotype. In contrast, MTD was observed at dose level 2 (100 mg/m(2)) in patients with the 6/7 genotype. Patients with the 6/7 genotype had a significantly higher area under the plasma time-concentration curve (0-infinity) SN-38 (P = 0.022) and biliary index (P = 0.030) than those with 6/6. The recommended starting doses of biweekly irinotecan for phase II/III were 150 mg/m(2) for patients with the UGT1A1 6/6 genotype and 70 mg/m(2) for those with the 6/7 genotype, respectively. The gene polymorphism should be considered when determining the precise recommended doses to be administered in phase I studies.
    Cancer Science 11/2009; 101(3):722-7. · 3.48 Impact Factor
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    ABSTRACT: We report a case of ascending colon cancer successfully treated for synchronous liver metastases with mFOLFOX6 after a resection of the primary tumor. A 79-year-old woman was diagnosed as having an ascending colon cancer with synchronous liver metastases. After right hemicolectomy, she was treated with mFOLFOX6. A partial response was observed after the fifth course and CEA decreased to a normal range (8 ng/mL). A complete response was observed after the ninth course and the treatment finished at the twelfth course. Sequentially, she was treated with UFT/LV/PSK after three courses of FOLFIRI regimen. The patient is alive without recurrence.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2009; 36(12):2184-6.
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    ABSTRACT: Although recent studies have shown that FoxP3 represent the most specific Treg marker only a few studies have reported on the presence of FoxP3(+)Treg in peripheral blood. Peripheral blood mononuclear cells (PBMC) were harvested from 37 healthy volunteers and 94 patients with gastrointestinal cancer. The prevalence of Treg co-expressing CD4(+)FoxP3(+) was analyzed using flow cytometry. The prevalence of Treg in the peripheral blood of gastrointestinal cancer patients was significantly higher than that in healthy volunteers (p=0.012). In early stage I cancer, Treg levels tended to be higher than those in healthy volunteers (p=0.069); these levels were significantly reduced after tumor resection (p=0.0027). The prevalence of Treg was increased in patients with gastrointestinal cancer, even in the early stages of the disease. Since Treg levels decreased after curative resection, it is possible that tumor cells may have induced and expanded the Treg pool.
    Anticancer research 06/2009; 29(5):1527-32. · 1.71 Impact Factor
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    ABSTRACT: Early delayed gastric emptying (DGE) is the most common complication after pylorus-preserving pancreatoduodenectomy (PpPD). Recently, a vertical antecolic reconstruction for duodenojejunostomy was recommended to decrease the incidence of early DGE in patients with Billroth II-type reconstruction after PpPD. However, Billroth I-type reconstruction (B-I) after PpPD is still favored in Japan. Twelve consecutive patients with B-I were prospectively enrolled. Our technique includes an end-to-side duodenojejunostomy and alignment of the stomach contours with fixation of the greater omentum to the abdominal wall in order to promote passage from the stomach through the jejunal loop. DGE was evaluated according to the consensus definition of the International Study Group of Pancreatic Surgery (ISGPS). DGE was absent, with the nasogastric tube removed within 3 days in all patients. Mean duration of nasogastric tube placement was 1.5 +/- 0.4 days. Mean maximum suction volume was 85 +/- 32 ml/day. Preliminary results were encouraging simply with relief of the outflow disturbance around the duodenojejunostomy in patients with B-I after PpPD. These findings warrant further prospective randomized trials at either multiple or high-volume centers.
    Journal of Hepato-Biliary-Pancreatic Surgery 04/2009; 16(3):300-4. · 1.60 Impact Factor
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    ABSTRACT: Human leukocyte antigen (HLA) class I expression is reportedly frequently reduced in cancer. We examined heat-shock protein (HSP) expression in hepatocellular carcinoma (HCC). HCV-related HCC was examined in 73 patients who had undergone hepatectomy, and the relationship between HSP70 and HLA class I expressions, clinicopathological factors and survival was evaluated. Immunohistochemically positive results for HSP70 and HLA class I were seen in 67 (92%) and 43 cases (59%), respectively, while 38 patients (52%) were positive for both. Increased HSP70 immunoreactivity was significantly associated with high histological grade of tumor differentiation (p = 0.0179), whereas reduced HLA class I immunoreactivity was significantly associated with large tumor size (p = 0.0082). No differences were apparent between disease-free and overall survival in regard to expression levels. These results suggest that HSP70 expression may be related to tumor differentiation and HLA class I loss may occur with tumor growth in HCV-related HCC.
    Anticancer research 03/2009; 29(2):539-44. · 1.71 Impact Factor
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    ABSTRACT: Pancreatic cancer has a poor prognosis. The clinical efficacy of immunotherapy using both dendritic cells pulsed with MUC1 peptide (MUC1-DC) and, cytotoxic T lymphocyte (CTL) sensitized with a pancreatic cancer, YPK-1, expressing MUC1 (MUC1-CTL) was evaluated. Twenty patients with unresectable or recurrent pancreatic cancer were enrolled. Peripheral blood mononuclear cells (PBMCs) were separated into adherent cells for induction of MUC1-DCs and floating cells for MUC1-CTLs. MUC1-DCs were generated by culture with granulocyte monocyte colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) and then exposed to MUC1 peptide and TNF-alpha. MUC1-CTLs were induced by co-culture with YPK-1 and then with interleukin-2 (IL-2). MUC1-DCs were injected intradermally and MUC1-CTLs were given intravenously. Patients were treated from 2 to 15 times. One patient with multiple lung metastases experienced a complete response. Five patients had stable disease. The mean survival time was 9.8 months. No grade II-IV toxicity was observed. Adoptive immunotherapy with MUC1-DC and MUC1-CTL may be feasible and effective for pancreatic cancer.
    Anticancer research 01/2008; 28(1B):379-87. · 1.71 Impact Factor
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    ABSTRACT: We examined retrospectively the efficacy of hepatic arterial infusion (HAI) chemotherapy comparing systemic treatment as adjuvant therapy after the curative resection of hepatic metastasis from colorectal cancer. Seventeen cases of HAI and 8 of the systemic treatment were enrolled in this study. We compared the pattern of recurrent sites and the overall survival rate between the two groups. There was no difference in a patients' background. Intrahepatic recurrence rate was lower and extrahepatic recurrence rate was higher in the HAI group, but not significant. The 1-, 3-, and 5-year overall survival rate was 94, 72, and 49% in the HAI group and 100, 100, and 50% in the systemic treatment group (p = 0.29), respectively. HAI chemotherapy did not contribute to the elongation of survival time in comparison with systemic treatment. This study indicates that there is no efficacy of HAI alone after the resection of hepatic metastasis from colorectal cancer and that there is need to use systemic chemotherapy together with HAI to prevent an extrahepatic recurrence.
    Gan to kagaku ryoho. Cancer & chemotherapy 12/2006; 33(12):1845-7.