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Specification factors regulate cell fate in part by interacting with transcriptional co‐regulators like CtBP to regulate gene expression. Here, we demonstrate that CtBP forms a complex or complexes with the Drosophila melanogaster Pax6 homolog Eyeless (Ey), and with Distal antenna (Dan), Distal antenna related (Danr), and Dachshund to promote eye and antennal specification. Phenotypic analysis together with molecular data indicate that CtBP interacts with Ey to prevent overproliferation of eye precursors. In contrast, CtBP,dan,danr triple mutant adult eyes have significantly fewer ommatidia than CtBP single or dan,danr double mutants, suggesting that the CtBP/Dan/Danr complex functions to recruit ommatidia from the eye precursor pool. Furthermore, CtBP single and to a greater extent CtBP,dan,danr triple mutants affect the establishment and maintenance of the R8 precursor, which is the founding ommatidial cell. Thus, CtBP interacts with different eye specification factors to regulate gene expression appropriate for proliferative vs. differentiative stages of eye development. Developmental Dynamics 239:2367–2385, 2010. © 2010 Wiley‐Liss, Inc.

BACKGROUND.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.METHODS.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.RESULTS.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 ≥16 years, tumor size ≥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.CONCLUSIONS.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 2007 © 2007 American Cancer Society.

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-a 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 Sci 2012; 103: 1625-1630 S ynovial sarcoma is a malignant tumor of soft tissue characterized by biphasic or monophasic histology, specific chromosomal translocation t(X;18), and its resultant SYT-SSX fusion genes.(1,2) Reported 5-year survival rates of patients with synovial sarcoma range from 64% to 77%.(3-7) In contrast, most metastatic or relapsed diseases remain incurable, indicating a need for new therapeutic options other than conventional surgery, radiotherapy, and chemotherapy.Antigen-specific peptide immunotherapy is one such option. (8)(9)(10)(11)(12) Previously, we demonstrated that SYT-SSX fusion gene-derived peptides (wild type and agretope modified) are recognized by circulating CD8 + T cells in HLA-A24 + patients with synovial sarcoma and elicit human leukocyte antigen (HLA)-restricted, tumor-specific cytotoxic responses. (13,14) Subsequent to these preclinical studies, we started a pilot clinical trial with a wild-type SYT-SSX-derived peptide vaccine. (15) In the present study, we evaluated immunologic and clinical outcomes of the vaccination trials using an agretope-modified SYT-SSX peptide and a combination of the peptide vaccine with adjuvant and interferon (IFN)-a.

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