Shigeru Furukawa

Yokohama City University, Yokohama, Kanagawa, Japan

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Publications (27)12.96 Total impact

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    ABSTRACT: Inostamycin is an inhibitor of cytidine 5′-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase. It significantly reduced epidermal growth factor (EGF)-induced in vitro invasion of the tongue carcinoma cell line, HSC-4, through reconstituted basement membrane Matrigel®. Since phosphatidylinositol (PI) 4,5-biphosphate is important for signal transduction through protein kinase C and actin reorganisation, we further examined the effect of inostamycin on production of two matrix metalloproteinases (MMPs), MMP-2 and -9, and on cell motility. Zymographic analysis showed that inostamycin suppressed pro-MMP-2 and pro-MMP-9 levels at a dose-dependent fashion, while MMP-2 activity was not significantly affected. By reverse transcription-polymerase chain reaction, it was found that inostamycin diminished steady state levels of MMP-2 and -9 but not membrane type 1-MMP mRNA expressions. Inostamycin partially blocked both EGF- and phorbol 12-myristate 13-acetate-stimulated pro-MMP- 9 production. A cytoplasmic calcium chelator (BAPTA-AM) dramatically elevated pro- MMP-9 and slightly elevated pro-MMP-2 secretions. EGF-stimulated motility of HSC-4 cells was suppressed by inostamycin treatment along with reduction of actin cytoskeletal reorganisation, filopodia formation and cdc42 expression. These results suggested that inostamycin would be useful for an anti-invasive agent in tongue cancer.
    Clinical and Experimental Metastasis 04/2012; 18(3):273-279. DOI:10.1023/A:1006798900743 · 3.73 Impact Factor
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    ABSTRACT: We present a case of nasal septal schwannoma. The patient was a 62-year-old female complaining of bilateral nasal obstruction. Anterior rhinoscopy revealed a smooth-surfaced mass arising from the nasal septum in both nasal cavities. Computed tomography scan showed a mass with enhancement in the two nasal cavities and the ethmoid sinuses, and this mass extended to the skull base. Lateral rhinotomy was performed under general anesthesia. The tumor arose from the nasal septum, occupied both nasal cavities, and extended to the anterior ethmoid sinuses. It was encapsulated and could be totally removed en bloc. Pathological examination of the excised specimen showed that it was an Antoni type A schwannoma. The tumor cells were immunoreactive for S-100 protein. The patient is doing well with no evidence of recurrence.
    Auris Nasus Larynx 05/2001; 28(2):173-5. DOI:10.1016/S0385-8146(00)00099-7 · 1.00 Impact Factor
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) is a malignant tumor with a high incidence in east Asian countries. Inactivation of cyclin-dependent kinase (CDK) inhibitors (CKIs) and overexpression of G1 cyclin has been thought to be important for tumor development. To determine whether reduction of CKI (p16 and p27) expression was associated with NPC development, we performed immunohistochemical staining of NPC specimens from 20 patients. We found that p16 and p27 proteins were negative in 8 of 20 and 16 of 20 cases, respectively; that either p16 or p27 proteins were negative in 17 of 20; and that both p16 and p27 were negative in 7 of 20. Excepting the cases in which both CKIs were negative, negativity of p27 alone was statistically higher than that of p16 (9/20 versus 1/20, P = .022), suggesting that the reduction of p27 protein is an important event for the multi-step process of NPC development.
    Cancer Detection and Prevention 02/2001; 25(5):414-9. · 2.52 Impact Factor
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    ABSTRACT: Inostamycin, which was recently isolated from Streptomyces sp. MH816-AF15 as an inhibitor of cytidine 5′-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase, caused a G1-phase accumulation in the cell cycle of small cell lung carcinomas. To investigate whether the cytostatic effect of inostamycin is restricted to lung carcinoma cell lines or applicable to other type of cells, we tested five oral squamous cell carcinoma (SCC) cell lines. Cell growth was suppressed in 62.5–125 ng/ml inostamycin in the culture medium in all oral cancer cell lines tested, with non-viable cells being <1%, indicating inostamycin is cytostatic on SCC cell lines. Decrease in cyclin D1 mRNA and protein expression due to the inostamycin treatment was accompanied by suppression of phosphorylated retinoblastoma susceptibility gene product (pRB-P) levels. Moreover, flow cytometric analysis showed that inostamycin induced an increase in G1/G0 cells (1.2–3.2 fold) over 24 h. These results suggest that inostamycin is a useful agent for tumour dormant cytostatic therapy for oral SCC.
    Cell Biology International 02/2001; 25(7-25):613-620. DOI:10.1006/cbir.2000.0706 · 1.64 Impact Factor
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    ABSTRACT: The antitumor effect of the angiogenesis inhibitor TNP470, O-(chloro-acetyl-carbamoyl) fumagillol, a synthetic analogue of fumagillin, was studied in vitro and in vivo on, cell line KB which produced interleukin (IL)-8. In vitro, TNP470 reduced the production of IL-8 from KB cells, the same as anti-IL-8 antibody (Ab.) The combination of anti-IL-8 Ab (10 micrograms/ml) and TNP470 (10 ng/ml) significantly inhibited the proliferation of KB cells, compared to no treatment (p < 0.05). Proliferation of KB cells was also significantly more suppressed by simultaneous treatment of cisplatin and TNP470 (1 mg/ml), than cisplatin alone. The in vivo antitumor effect of TNP470 was studied using anti-IL-8 Ab, anti-vascular endothel growth factor (VEGF) Ab, and TNP470, in administered by different routes, i.e., intratumoral (i.t.), intraperitoneal (i.p.), and intravenous. TNP470 (10 mg/ml) showed an antitumor effect, and intratumoral administration of TNP470 was the most effective route. Combined administration of anti-IL-8 Ab (i.p.) and TNP470 (i.t.) reduced tumor volume more than anti-IL-8 Ab alone did. These results suggest that the combination of TNP470, cisplatin, and anti-IL-8 Ab could be a beneficial treatment for solid tumors of the head and neck.
    Nippon Jibiinkoka Gakkai Kaiho 07/2000; 103(7):821-8. DOI:10.3950/jibiinkoka.103.821
  • Nihon Kikan Shokudoka Gakkai Kaiho 01/1999; 50(6):609-614. DOI:10.2468/jbes.50.609
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    ABSTRACT: Hypopharyngeal carcinoma (HPC) has a poor prognosis. We investigated the expression of cyclin D1 in 34 advanced HPCs, and the value of cyclin D1 expression was evaluated as a predictive marker in terms of the prognosis of HPC, compared with other clinical factors. Using immunohistochemical staining, 20 of 34 patients showed positive immunoreactivity for cyclin D1. The statistical trend of the survival rate was lower in the cyclin D1-positive patients than in the cyclin D-negative ones (p = 0.0805). The predictive factors for the survival rate were effectiveness of neo-adjuvant chemotherapy (F = 8.698) (p = 0.0066), cyclin D1 expression (F = 6.244) (p = 0.0191) and N classification (F = 5.037) (p = 0.0335). The cyclin D1-positive patients had approximately four-fold higher mortality than the cyclin D1-negative ones. These data indicate that the expression of cyclin D1, in advanced patients with hypopharyngeal carcinoma is a useful marker for prognosis.
    The Journal of Laryngology & Otology 07/1998; 112(6):552-5. DOI:10.1017/S0022215100141064 · 0.70 Impact Factor
  • Nihon Kikan Shokudoka Gakkai Kaiho 01/1995; 46(3):253-257. DOI:10.2468/jbes.46.253
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    ABSTRACT: Randomized studies on the efficacy of two courses of different types of chemotherapy, including cisplatin and 5-fluorouracil (5-FU), were performed on 130 previously untreated cases with advanced squamous cell carcinomas of the head and neck. Cisplatin, followed by 120-hr continuous 5-FU infusion given in the conventional way, was administered to 60 patients (Group A), while cisplatin was administered 72 hr after the initiation of continuous 5-FU infusion in 70 other patients (Group B). The overall response rates (complete response plus partial response) were 58% in group A and 69% in group B, respectively. A superior complete response rate was obtained in cases receiving modified chemotherapy (10% in group A vs 20% in group B). There was no significant difference in the incidence of side effects between the two groups. These findings indicate that the modified cisplatin plus 5-FU combination chemotherapy tested here is more efficacious regimen than that of the conventional one to achieve high complete response rate and subsequently, to improve the survival of advanced carcinoma cases of the head and neck.
    Auris Nasus Larynx 02/1994; 21(3):181-5. DOI:10.1016/S0385-8146(12)80142-8 · 1.00 Impact Factor
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    ABSTRACT: Induction chemotherapy, followed by definitive treatment, was performed in patients with advanced squamous-cell carcinoma of the head and neck. In this study, carried out between 1984 and 1991, testing the effectiveness of multimodality therapy in patients with previously untreated advanced (stage III and IV) squamous-cell carcinoma of the pharynx, patients received two different induction chemotherapy regimens: cisplatin, vincristine (Oncovin) plus peplomycin (COP), and cisplatin plus continuous 120-hr 5-fluorouracil (5-FU) infusion (CF) for two courses. Overall response rates (complete response plus partial response) to each of the two induction chemotherapy regimens were high: 76 and 82%, respectively. Superior complete response rate in the group receiving CF therapy was 16% versus 10% for COP therapy. Responders to induction chemotherapy had significantly better survival compared with non-responders. The toxicity of these two regimens was tolerable and manageable. It is indispensable to develop the more efficacious chemotherapy regimen with the potential to induce complete disappearance of tumors in patients with advanced head and neck carcinomas.
    Auris Nasus Larynx 02/1994; 21(3):186-92. DOI:10.1016/S0385-8146(12)80143-X · 1.00 Impact Factor
  • Kampo Medicine 01/1994; 45(2):401-405. DOI:10.3937/kampomed.45.401
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    ABSTRACT: Metastatic tumours involving the head and neck region are rare. Over the past 18 years, seven such cases were treated at our clinic. Of those, four were in one of the paranasal sinuses, three had arisen from a primary hepatocellular carcinoma and one from an osteogenic fibrosarcoma of the leg. In the remaining three cases, metastases to the larynx, the tonsil, and the parotid gland arose from a primary renal cell carcinoma, a thyroid carcinoma, and a breast carcinoma, respectively. In metastatic tumours, the primary site can often be identified by the histopathological features. Accordingly, when malignant head and neck tumours are suspected of being metastatic in character, it is important to search carefully for the primary site.
    The Journal of Laryngology & Otology 01/1994; 107(12):1171-3. DOI:10.1017/S0022215100125599 · 0.70 Impact Factor
  • M Tsukuda, S Furukawa, S Sawaki, A Kubota
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    ABSTRACT: Recombinant human granulocyte colony-stimulating factor (rG-CSF) was used for the amelioration of neutropenia caused by cisplatin-based chemotherapy in head and neck cancer patients. For a dose-finding study of rG-CSF, 11 patients, who had levels of absolute neutrophil counts below 500/mm3 in peripheral blood, were administered rG-CSF subcutaneously at a dose of 1 or 2 micrograms/kg for 5 days. A 'useful' rate in 1 and 2 micrograms/kg was obtained in 71.4 and 100% of patients, respectively. In 6 patients, the clinical utility of rG-CSF at a dosage of 2 micrograms/kg from the day after chemotherapy for 10 consecutive days was observed. The percentage of 'very useful' evaluations was 83.3% (5/6). No side effects or abnormal laboratory findings were observed in any patients after administration of rG-CSF.
    ORL 01/1994; 56(2):101-4. DOI:10.1159/000276619 · 0.67 Impact Factor
  • 01/1994; 20(1):18-22. DOI:10.5981/jjhnc1974.20.18
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    ABSTRACT: In this study, the utility and safety of granisetron alone (Group G) and granisetron plus hydroxyzine hydrochloride (Group G/H) for nausea and vomiting were evaluated in patients with head and neck cancer treated by cisplatin-containing chemotherapy. There was no statistically significant difference between the two groups in the severity of nausea or frequency of vomiting, although all patients in the G/H group showed complete response (no nausea or vomiting) from the fifth day after cisplatin administration. The clinical utility rate was higher in Group G/H than in Group G. The only side effect observed was headache in one patient from Group G. No drug-related abnormality in laboratory tests was observed. These results demonstrate that the antiemetic efficacy of granisetron can be augmented by the addition of hydroxyzine hydrochloride, providing superior control of emesis induced by cisplatin-containing chemotherapy.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/1993; 20(13):2037-41. DOI:10.1016/0959-8049(95)00192-L
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    ABSTRACT: In order to select the most cytotoxic effector cells for adoptive immunotherapy, lymphokine activated killer (LAK) cells, tumor infiltrating lymphocytes (TILs) and autologous mixed lymphocyte tumor cell culture (MLTC) cells derived from peripheral blood mononuclear cells (PBMC) in the same subject with head and neck carcinomas were prepared. The autologous tumor cell killing activity and cell surface phenotypes of each of the three effector cells were studied. MLTC cells cultured with interleukin-2 (IL-2) showed the strongest cytotoxic activity among these three different effector cells. Although TILs had suppressed killing activity immediately after isolation, after successive cultivations with IL-2, a cytotoxic activity against autologous tumor cells stronger than that of LAK cells appeared. Both IL-2 stimulated MLTC cells and TILs showed an enrichment of CD8 positive and CD11 negative cells in a CD3 positive subpopulation.
    Biotherapy 02/1993; 6(2):155-61. DOI:10.1007/BF01877429
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    ABSTRACT: Sensitivities to recombinant human tumor necrosis factor-alpha (TNF-alpha) and chemotherapeutic agents (cisplatin, peplomycin, methotrexate) were evaluated in 20 tumor cells of head and neck squamous cell carcinomas, using a dye uptake method. Also, numbers of TNF receptors of these tumor cells were measured by Scatchard plot analysis. There was no relationship between the number of TNF-alpha receptors and the sensitivity to TNF-alpha. Furthermore, there was no correlation between the sensitivity to TNF-alpha and that to chemotherapeutic drugs, nor between the sensitivity to TNF-alpha and the clinical response to chemotherapy including of cisplatin and peplomycin. The sensitivity to TNF-alpha was higher in poorly differentiated carcinomas than in well differentiated ones.
    Biotherapy 02/1993; 6(4):239-44. DOI:10.1007/BF01878352
  • Gan to kagaku ryoho. Cancer & chemotherapy 05/1992; 19(4):553-6.
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    ABSTRACT: A cell line was established from a patient with malignant fibrous histiocytoma, which had originated in the maxillary sinus. Using this cell line, sensitivity to chemotherapeutic agents and cytotoxicity against various immunoeffecter cells were tested. Results: This MFH cell line was sensitive in some degree to adriamycin, 5-fluorouracil, cisplatin, peplomycin, and methotrexate at high doses, but insensitive to mitomycin-C, vincristine and cyclophosphamide. Furthermore, this cell line showed no sensitivity to cytolytic cytokines, such as tumor necrosis factor-alpha and interferon-gamma. Lymphokine activated killer (LAK) cells and lymphokine activated tumor infiltrating lymphocytes (LA-TIL), induced by culture of peripheral blood lymphocytes and TIL respectively with rIL-2 showed high NK and LK activities and remarkable anti-autologous tumor ability.
    Nippon Jibiinkoka Gakkai Kaiho 03/1992; 95(2):207-13. DOI:10.3950/jibiinkoka.95.207
  • 01/1992; 18(2):148-152. DOI:10.5981/jjhnc1974.18.2_148