Takeshi Ishii

Chiba Cancer Center, Tiba, Chiba, Japan

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Publications (27)65.57 Total impact

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    ABSTRACT: Osteosarcoma as second malignancy of childhood cancers rarely occurs, and its clinical characteristics are unclear.
    International journal of clinical oncology. 07/2014;
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    ABSTRACT: Background and Objectives Infiltrative growth, frequently observed in undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS), is often associated with a positive surgical margin as well as a local failure. The purpose of our study was to determine whether the radiographic growth patterns were associated with the outcomes of patients with UPS and MFS.Methods We reviewed 89 patients diagnosed with UPS or MFS and underwent initial surgery at our institute between 1994 and 2011. Growth patterns were assessed radiographically on preoperative MRI. Clinicopathological factors were collected and uni- and multivariate analyses were performed for survival.ResultsInfiltrative growth was observed in 21 patients (24%), which correlated with superficial tumors and positive surgical margin. Infiltrative growth correlated with poor disease-specific and distant failure-free survivals relative to non-infiltrative growth. Multivariate analysis confirmed that these factors remained as significant factors. Patients with non-infiltrative tumors resected inadequately exhibited slightly more favorable local control with postoperative radiotherapy, although no clinical benefit was seen for those with infiltrative tumors.Conclusions Infiltrative growth was an adverse prognostic factor for not only local control, but also disease-specific and metastasis-free survival in patients with UPS and MFS. Radiotherapy could not salvage inadequately resected infiltrative tumors. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 06/2014; · 2.64 Impact Factor
  • Journal of Orthopaedic Science 09/2013; · 0.96 Impact Factor
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    ABSTRACT: The occurrence of osteosarcoma in elderly patients has recently been increasing, and the outcome is poor. This multi-institutional retrospective study was conducted to investigate clinical features and prognostic factors in patients older than 40 years with osteosarcoma. Patients with conventional high-grade osteosarcoma older than 40 years were recruited to this study. Secondary osteosarcoma arising from Paget's disease or irradiated bones was excluded. Information on tumor- and treatment-related factors was collected and statistically analyzed. The median follow-up was 57 months (range 8-244 months) for all surviving patients. A total of 86 patients were enrolled in this study. The median age at diagnosis was 61 years. Surgery and chemotherapy were conducted in 73 and 63 % of all patients, respectively. The 5-year overall and event-free survival rates were 38.8 and 34.0 %, respectively. Tumor site (extremity 57.9 %; axial 19.0 %; p < 0.0001), metastasis at diagnosis (yes 12.2 %; no 48.3 %; p < 0.0091), and definitive surgery (yes 56.2 %; no 10.6 %; p < 0.0001) were associated with overall survival. Although patients without metastasis who received definitive surgery were regarded as good candidates for chemotherapy, the addition of chemotherapy did not have any impact on the outcome (yes 63.4 %; no 65.2 %; p = 0.511). The present study revealed the distinct clinical features, such as the high incidence of truncal tumors or metastasis at diagnosis, in patients older than 40 years with osteosarcoma. Additionally, prognostic factor analyses revealed that tumor site, metastasis at diagnosis, definitive surgery, and surgical margins were significant prognostic factors, whereas chemotherapy did not influence survival.
    Annals of Surgical Oncology 08/2013; · 4.12 Impact Factor
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    ABSTRACT: BACKGROUND: Treatment for unresectable Ewing's sarcoma family of tumors (ESFT) is a formidable challenge because of its high tendency for local and distant failure. Recently, carbon-ion radiotherapy (CIRT) has been applied to unresectable bone and soft tissue sarcoma. Additionally, high-dose chemotherapy (HDC) with stem cell rescue has been used to improve the survival of patients with relapsed ESFT. Here we report our experience with CIRT and HDC in the treatment of unresectable ESFT. METHODS: Five unresectable ESFT patients including 4 who underwent CIRT and HDC and one who underwent CIRT from 1999-2009 were retrospectively studied. After neoadjuvant chemotherapy, CIRT was conducted at the National Institute of Radiological Sciences in Chiba as local therapy. Consecutively, we employed HDC including busulfan, melphalan, and thiotepa with stem cell rescue. RESULTS: Two patients showed tumor shrinkage after CIRT, including 1 patient who achieved partial response. No severe acute toxicity related to CIRT was observed. Local failure was observed in only 1 patient at 22 months after CIRT. Four patients conducted HDC with stem cell rescue after CIRT and 1 patient suffered from veno-occlusive disease just after HDC. Distant failure was observed in 3 patients after completion of the treatment. CONCLUSIONS: CIRT and HDC for unresectable ESFT patients show favorable local control, with unsatisfactory results for distant control.
    International Journal of Clinical Oncology 10/2012; · 1.41 Impact Factor
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    ABSTRACT: In the present study, we evaluated the safety and effectiveness of SYT-SSX-derived peptide vaccines in patients with advanced synovial sarcoma. A 9-mer peptide spanning the SYT-SSX fusion region (B peptide) and its HLA-A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14-day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freund's adjuvant and then administered subcutaneously six times at 14-day intervals. In addition, interferon-α was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six-injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed-type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.
    Cancer Science 06/2012; 103(9):1625-30. · 3.48 Impact Factor
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    ABSTRACT: Posttraumatic stress symptom (PTSS) and posttraumatic growth (PTG) were surveyed in parents of childhood, adolescent and young adult patients with high-grade osteosarcoma. A questionnaire survey was performed in parents of patients with osteosarcoma (51 families). The Impact of Event Scale-Revised (IES-R) and posttraumatic growth inventory (PTGI) were employed for the evaluation of PTSS and PTG, respectively. The mean scores were compared with those in preceding studies employing the same scales. In addition, the correlation between the IES-R and PTGI scores was investigated in the parents. Fifty-eight subjects of 34 families (30 fathers and 28 mothers) replied to the questionnaire. The mean IES-R score in the parents was 18.5, which was higher than that in patients with osteosarcoma (9.7) in our previous study. The mean PTGI score in the parents was 44.9, which was higher than that in university students (33.9) reported by Taku et al. A positive correlation was noted between the IES-R and PTGI scores in the parents. The PTSS level tended to be higher in the parents rather than in patients with osteosarcoma. The PTG level increased as the PTSS level rose in the parents.
    International Journal of Clinical Oncology 07/2011; 17(3):272-5. · 1.41 Impact Factor
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    ABSTRACT: Imatinib myselate is a molecularly targeted drug that inhibits Abl tyrosine kinase, as well as type III tyrosine kinase receptors such as platelet-derived growth factor receptor (PDGFR), KIT, colony-stimulating factor 1 receptor (CSF-1R), and discoidin domain receptor (DDR). Ph1 chromosome-positive chronic myeloid leukemias (CMLs), KIT-positive gastrointestinal stromal tumors (GISTs), and PDGFR-positive dermatofibrosarcoma protuberans (DFSP) have been reported to be responsive to imatinib treatment. We conducted a multicenter Phase II trial of imatinib in patients with relapsed or refractory KIT-positive (excluding GISTs) or PDGFR-positive sarcomas. Patient ages ranged from 12 and 75 years. Eligibility criteria included (1) metastatic sarcomas with a definitive diagnosis based on histopathology or that were completely unresectable and locally advanced; (2) relapsed or refractory cases that had completed standard treatment; and (3) a tumor confirmed by immunohistochemical staining to be KIT- or PDGFR-positive. A 600-mg dose of imatinib was administered to patients once a day, with each patient receiving six courses of the drug and each course lasting 4 weeks. In cases categorized as stable or progressive, the imatinib dose was increased to 800 mg/day administered twice daily. A total of 25 patients who met the eligibility criteria were enrolled in the trial; 22 were evaluated for response. The response rate with a 600 mg/day dose of imatinib was 4.5% (0 complete response, 1 partial response). There were no other objective responses after increasing imatinib to 800 mg/day (0/10). We estimated 50% progression-free survival to be 61.0 days for an imatinib dose of 600 mg/day based on the Kaplan-Meier method. Side effects of imatinib were generally similar to those observed in previous clinical trials. Our results did not indicate effectiveness of imatinib monotherapy at a dose of 600 or 800 mg/day in patients with relapsed or refractory KIT-positive (excluding GISTs) or PDGFR-positive sarcomas. Our findings suggest the need to evaluate the synergistic effect of combination therapy with other anticancer drugs.
    Journal of Orthopaedic Science 09/2010; 15(5):654-60. · 0.96 Impact Factor
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    ABSTRACT: Polyhomeotic homolog 3 (PHC 3) is a member of the human polycomb complex and has been regarded as a candidate tumor suppressor of osteosarcoma. In the present paper, we performed a mutation survey and PHC3 expression analysis by quantitative real-time PCR using 10 osteosarcoma cell lines and 42 primary osteosarcoma samples. Relative PHC3 expression values of clinical samples were analyzed with clinical outcomes, and it was suggested that lower PHC3-expressing patients had significantly worse overall survival. Relative PHC3 values of clinical samples were less than those of normal bone tissues, whereas they were greater than those of cell lines. By denaturing high performance liquid chromatography analysis and direct sequencing, we found a PHC3 missense mutation in U2OS cells, which resulted in arginine56 to proline substitution. The same point mutation existed in four of 42 primary osteosarcoma samples. Regarding functional analysis, PHC3 expression significantly suppressed the colony formation of tumor cells. Intriguingly, polycomb repressive complex 1 members, Bmi1 and Ring1b proteins, were reduced in PHC3-expressing osteosarcoma cells. Deletion mutant PHC3 expression suggested that the carboxyl terminus of PHC3 has a role in suppression; the above-mentioned point mutation of PHC3 also lost inhibitory activities. Conversely, Bmi1 expression reduced PHC3 at the mRNA level and induced the proliferation of osteosarcoma cells. Taken together, we confirmed the role of PHC3 as a tumor suppressor in osteosarcoma cells and found that PHC3-dependent tumor suppression may be caused by modification of the composition of polycomb repressive complex 1 in cancer cells.
    Cancer Science 07/2010; 101(7):1646-52. · 3.48 Impact Factor
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    ABSTRACT: The psychosocial outcomes in long-term survivors of osteosarcoma were investigated. A questionnaire concerning the psychosocial status was completed by 30 long-term survivors of osteosarcoma. The family APGAR was employed for the evaluation of family function, social support questionnaire (SSQ) for social support, impact of event scale-revised (IES-R) for posttraumatic stress symptoms (PTSS), and posttraumatic growth inventory (PTGI) for posttraumatic growth (PTG). The family APGAR and SSQ scores were comparable to those of controls. The IES-R score was low, showing a low incidence of PTSS. The PTGI score was high, revealing marked PTG. On multiple regression analysis regarding the IES-R as a dependent variable, the family APGAR was associated with the IES-R. On multiple regression analysis regarding the PTGI as a dependent variable, the age at diagnosis, state of the affected limb and SSQ were associated with the PTGI. The incidence of PTSS was low, and PTG was marked in the long-term survivors of osteosarcoma. A high age at onset and amputation of the affected limb were associated with PTG. Support of the family function reduces PTSS, and the strengthening of social support facilitates PTG.
    Anticancer research 10/2009; 29(10):4287-90. · 1.71 Impact Factor
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    ABSTRACT: Osteosarcoma is the most frequent primary malignant bone tumor. In Europe and the United States, its prognosis has been greatly improved by the use of multimodal treatment, including preoperative and postoperative chemotherapy as well as surgery. In Japan, however, only a few clinical studies on osteosarcoma have been carried out. To evaluate the efficacy of neoadjuvant chemotherapy on nonmetastatic, operable osteosarcoma arising in the extremities, a prospective multi-institutional phase II trial, the Neoadjuvant Chemotherapy for Osteosarcoma (NECO) study, was conducted. Preoperative chemotherapy included high-dose methotrexate (HD-MTX), cisplatin (CDDP), and adriamycin (ADR). If the induction therapy was assessed as not effective, high-dose ifosfamide (IFO) was added to the chemotherapy regimen. A total of 124 patients were enrolled in this trial, and ultimately 113 patients were eligible. The 5-year overall survival (OAS) and event-free survival (EFS) rates in the NECO study were 77.9% and 65.5%, respectively. A good histological response to the induction chemotherapy resulted in favorable OAS (78.7%). The patients assessed as poor histological responders with progressive disease after the induction chemotherapy exhibited comparable outcomes (OAS 89.5%, EFS 68.2%). There were no significant differences between the OAS and EFS rates of the patients in terms of response to preoperative chemotherapy. We analyzed the results of the intensive neoadjuvant chemotherapy and the effects of adding IFO on patients with osteosarcoma in Japan. The results suggest efficacy of the high-dose IFO addition to the standard three-drug chemotherapy regimen. However, a randomized clinical study is needed to establish the true impact of IFO on patients with osteosarcoma.
    Journal of Orthopaedic Science 08/2009; 14(4):397-404. · 0.96 Impact Factor
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    ABSTRACT: To investigate the marital status and fertility in long-term survivors of high-grade osteosarcoma. We surveyed the marital rate (number of married persons/total number of persons) in 46 long-term survivors of osteosarcoma who were treated in our hospital between 1976 and 2002. In addition, we examined the fertility rate (number of persons having offspring/number of married persons) in 29 married patients. The participants were divided into 2 groups: one group (MC) in which moderate-dose chemotherapy was performed between 1976 and 1986; and another group (IC) in which intensive-dose chemotherapy was performed between 1987 and 2002. In each group, the fertility rate was investigated. As controls, we surveyed the marital and fertility rates in 52 siblings of the patients. In the patients, the marital rate was 63.0% (29/46). There was no significant difference in the marital rate between the patients and their siblings. In the patients, the overall fertility rate was 58.6% (17/29). The fertility rate of male patients in the IC group (16.7%, 1/6) was significantly lower than that of their male siblings (76.5%, 13/17) (p = 0.018). These results suggest that recently intensified chemotherapy for osteosarcoma affects fertility in long-term male survivors.
    Anticancer research 03/2009; 29(2):763-7. · 1.71 Impact Factor
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    ABSTRACT: The radiographic evaluation of the response to preoperative chemotherapy for bone and soft tissue sarcomas is based mostly on the change in primary tumor size before and after chemotherapy, as is done for many solid cancers. Its prognostic correlation, however, has hardly been validated. We conducted a retrospective validation study of the Japanese Orthopaedic Association (JOA) radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas as a JOA Committee on Musculoskeletal Tumors cooperative study. A total of 125 consecutive patients with high-grade bone (n = 77) and soft tissue (n = 48) sarcomas treated with neoadjuvant chemotherapy and definitive surgery in 25 tertiary referral hospitals were selected for the study. We investigated the correlation between the tumor size-based radiographic response evaluation criteria of preoperative chemotherapy for bone and soft tissue sarcomas provided by the JOA Committee on Musculoskeletal Tumors (hereafter called the JOA criteria) and the patients' overall survival using the Kaplan-Meier method and the log-rank test. The JOA criteria correlated relatively well with survival for malignant bone tumors (mostly comprising osteosarcoma and Ewing's sarcoma) but not for soft tissue sarcomas, suggesting that the tumor size-based radiographic evaluation criteria for the response to preoperative chemotherapy in patients with soft tissue sarcomas is invalid. The JOA criteria, based on the change in primary tumor size, is valid for malignant bone tumors but invalid for soft tissue sarcomas. Other new evaluation modalities of the response to preoperative chemotherapy using innovative functional imaging techniques are needed for soft tissue sarcomas.
    Journal of Orthopaedic Science 08/2008; 13(4):304-12. · 0.96 Impact Factor
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    ABSTRACT: To develop peptide-based immunotherapy for osteosarcoma, we previously identified papillomavirus binding factor (PBF) as a cytotoxic T lymphocytes (CTL)-defined osteosarcoma antigen in the context of human leukocyte antigen (HLA)-B55. In the present study, we analyzed the distribution profile of PBF in 83 biopsy specimens of osteosarcomas and also the prognostic impact of PBF expression in 78 patients with osteosarcoma who had completed the standard treatment protocols. Next, we determined the antigenic peptides from PBF that react with peripheral T lymphocytes of HLA-A24(+) patients with osteosarcoma. Immunohistochemical analysis revealed that 92% of biopsy specimens of osteosarcoma expressed PBF. PBF-positive osteosarcoma conferred significantly poorer prognosis than those with negative expression of PBF (P = 0.025). In accordance with the Bioinformatics and Molecular Analysis Section score, we synthesized 10 peptides from the PBF sequence. Subsequent screening with an HLA class I stabilization assay revealed that peptide PBF A24.2 had the highest affinity to HLA-A24. CD8(+) T cells reacting with a PBF A24.2 peptide were detected in eight of nine HLA-A24-positive patients with osteosarcoma at the frequency from 5 x 10(-7) to 7 x 10(-6) using limiting dilution/mixed lymphocyte peptide culture followed by tetramer-based frequency analysis. PBF A24.2 peptide induced CTL lines from an HLA-A24-positive patient, which specifically killed an osteosarcoma cell line that expresses both PBF and HLA-A24. These findings suggested prognostic significance and immunodominancy of PBF in patients with osteosarcoma. PBF is the candidate target for immunotherapy in patients with osteosarcoma.
    Cancer Science 03/2008; 99(2):368-75. · 3.48 Impact Factor
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    ABSTRACT: Ewing sarcoma family of tumors (ESFT) of bone is extremely rare in Japan. The objectives of the current study were to assess the clinical outcome and prognostic factors of patients with ESFT of bone in Japan and to compare them between Euro-American and Japanese populations. The authors conducted a retrospective analysis of 243 patients who were treated for ESFT of bone in Japan between 1981 and 2003. Local therapy was surgery in 35% of patients, surgery combined with radiotherapy in 40% of patients, radiotherapy alone in 22% of patients, and no local treatment in 3% of patients. All but 3 patients received various regimens of multidrug chemotherapy. The median patient age was 16 years. The primary disease sites were the trunk in 53% of patients and the extremities in 47% of patients. Forty-one patients had metastases at presentation. The median follow-up was 66 months. A univariate survival analysis demonstrated that patients who had metastases at presentation, primary site in the trunk, age >or=16 years, tumor size >or=10 cm, tumor that responded poorly to induction chemotherapy, and local treatment with radiotherapy alone had a significantly worse event-free survival (EFS). A multivariate analysis further verified that the former 3 factors were significant adverse prognostic factors. Of 201 patients with localized disease, 45 patients who received current chemotherapy regimens that included ifosfamide and etoposide had a significantly better 5-year EFS rate (67.6%) compared with other patients. The clinical outcome of patients with localized ESFT of bone in Japan has improved markedly with the use of current chemotherapy regimens that include ifosfamide and etoposide and has become comparable to the outcomes observed in other major series of Euro-American patients. The prognostic factors are also almost identical.
    Cancer 03/2007; 109(4):767-75. · 5.20 Impact Factor
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    ABSTRACT: This study aimed to evaluate the quality of life (QOL) in long-term survivors of high-grade osteosarcoma. The QOL of 33 long-term survivors of osteosarcoma was evaluated using the Short Form 36 (SF-36) Health Survey Questionnaire. The patients were divided into a limb-sparing group (14 patients) and an amputation group (19 patients), and the QOL was compared between them. In addition, limb function was assessed using the system for functional evaluation of the limb of the American Musculoskeletal Tumor Society (MSTS score), and the relationship between the MSTS score and SF-36 scores was studied. The QOL of all patients was lower than the national standard concerning physical functioning but was higher than the national standards in the other parameters. The QOL of the limb-sparing group was significantly better than that of the amputation group with regard to social functioning. No significant correlation was noted between the MSTS score and the mental component summary. The QOL of the long-term survivors of osteosarcoma was satisfactory except for physical functioning. Limb-sparing surgery improved the QOL of long-term survivors of osteosarcoma with regard to social functioning, but no correlation was noted between limb function and mental QOL.
    Anticancer research 01/2007; 27(5B):3621-4. · 1.71 Impact Factor
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    ABSTRACT: Doxorubicin and ifosfamide are the two most active agents used to treat soft tissue sarcomas. However, because of their overlapping side effects, concurrent administration to achieve optimal doses of each agent is difficult. We therefore conducted a Phase II trial to investigate the efficacy and feasibility of a novel alternating sequential chemotherapy regimen consisting of high dose ifosfamide and doxorubicin/cyclophosphamide in advanced adult non-small round cell soft tissue sarcomas. Adult patients with non-small round cell soft tissue sarcomas were enrolled. The treatment consisted of four sequential courses of chemotherapy that was planned for every 3 weeks. Cycles 1 and 3 consisted of ifosfamide (14 g/m(2)), and cycles 2 and 4 consisted of doxorubicin (60 mg/m(2)) and cyclophosphamide (1200 mg/m(2)). Forty-two patients (median age 47 years) were enrolled. Of the 36 assessable patients, 1 complete response and 16 partial responses were observed, for a response rate of 47.2%. Responses were observed in 57% of patients who had received no previous chemotherapy and 13% of those who had previously undergone chemotherapy. Grade 3-4 neutropenia was observed during 70% of all cycles. Sequential administration of high-dose ifosfamide and doxorubicin/cyclophosphamide has promising activity with manageable side effects in patients with advanced adult non-small round cell soft tissue sarcomas.
    Journal of Orthopaedic Science 06/2005; 10(3):258-63. · 0.96 Impact Factor
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    ABSTRACT: BACKGROUND: Synovial sarcoma is a high-grade malignant tumor of soft tissue, characterized by the specific chromosomal translocation t(X;18), and its resultant SYT-SSX fusion gene. Despite intensive multimodality therapy, the majority of metastatic or relapsed diseases still remain incurable, thus suggesting a need for new therapeutic options. We previously demonstrated the antigenicity of SYT-SSX gene-derived peptides by in vitro analyses. The present study was designed to evaluate in vivo immunological property of a SYT-SSX junction peptide in selected patients with synovial sarcoma. METHODS: A 9-mer peptide (SYT-SSX B: GYDQIMPKK) spanning the SYT-SSX fusion region was synthesized. Eligible patients were those (i) who have histologically and genetically confirmed, unresectable synovial sarcoma (SYT-SSX1 or SYT-SSX2 positive), (ii) HLA-A*2402 positive, (iii) between 20 and 70 years old, (iv) ECOG performance status between 0 and 3, and (v) who gave informed consent. Vaccinations with SYT-SSX B peptide (0.1 mg or 1.0 mg) were given subcutaneously six times at 14-day intervals. These patients were evaluated for DTH skin test, adverse events, tumor size, tetramer staining, and peptide-specific CTL induction. RESULTS: A total of 16 vaccinations were carried out in six patients. The results were (i) no serious adverse effects or DTH reactions, (ii) suppression of tumor progression in one patient, (iii) increases in the frequency of peptide-specific CTLs in three patients and a decrease in one patient, and (iv) successful induction of peptide-specific CTLs from four patients. CONCLUSIONS: Our findings indicate the safety of the SYT-SSX junction peptide in the use of vaccination and also give support to the property of the peptide to evoke in vivo immunological responses. Modification of both the peptide itself and the related protocol is required to further improve the therapeutic efficacy.
    Journal of Translational Medicine 02/2005; 3(1):1. · 3.46 Impact Factor
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    ABSTRACT: The appearance of distant metastasis is a fatal sign in patients with soft tissue sarcoma. Therefore, we studied the risk factors associated with distant metastasis that appear in malignant fibrous histiocytoma. The study group comprised sixty patients treated for malignant fibrous histiocytoma at our hospital between 1991 and 2002. We retrospectively studied whether age, tumor size, tumor site, developmental form, surgical margin, local recurrence, histological subtype, vascular invasion and histological grade are risk factors associated with the appearance of distant metastasis. A univariate analysis showed that, for those patients older than 70 years of age, insufficient surgical margin, the presence of local recurrence and vascular invasion are significant risk factors associated with the appearance of distant metastasis. A multivariate analysis showed only the presence of vascular invasion to be a significant risk factor as well. Histological vascular invasion by tumors is a risk factor associated with distant metastasis that appears in malignant fibrous histiocytoma. Taking early measures for patients with vascular invasion is necessary to improve the prognosis.
    Anticancer research 01/2005; 25(2B):1337-42. · 1.71 Impact Factor
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    ABSTRACT: To investigate the effects of anchor substitutions in SYT-SSX junction peptide, an HLA-A24 anchor residue (position 9) of the SYT-SSX B peptide (GYDQIMPKK) was substituted to more favorable residues according to the HLA-A24-binding motif. Among four substitutes constructed, a substitute with isoleucine (termed K9I peptide) most apparently enhanced the affinity for HLA-A24 molecule. Subsequent in vitro CTL induction analysis using PBMCs of 15 HLA-A24(+) synovial sarcoma patients revealed that the original B peptide allowed to induce synovial sarcoma-specific CTLs from 7 patients (47%), whereas such CTLs were inducible from 12 patients (80%) with K9I peptide. Moreover, the extent of cytotoxicity against HLA-A24(+) synovial sarcoma cell lines was higher in K9I peptide-induced CTLs than B peptide-induced CTLs. Influence of anchor substitution on peptide/TCR interaction was evaluated by cytotoxicity assays against autologous cells and tetramer analysis. CTLs induced from a synovial sarcoma patient using K9I peptide did not lyse autologous PHA blasts or EBV-infected B cells. In vitro stimulations of PBMCs from 5 HLA-A24(+) synovial sarcoma patients with K9I peptide increased the frequency of T cells reacting with both HLA-A24/K9I peptide tetramer and HLA-A24/B peptide tetramer. In contrast, the frequency of T cells reacting with HLA/HIV-derived peptide tetramer remained low. These findings support the validity in design of anchor residue substitution in SYT-SSX fusion gene-derived peptide, and provide a potential clue to the current stagnation in vaccination trials of fusion gene-derived natural junction peptides.
    The Journal of Immunology 08/2004; 173(2):1436-43. · 5.52 Impact Factor