Major causes of head and neck squamous cell carcinoma (HNSCC)-related deaths are cervical node and distant metastasis. We previously demonstrated that overexpression of the DNA double-strand break repair protein Nijmegen breakage syndrome 1 (NBS1) is a prognostic marker of advanced HNSCCs. Epithelial-mesenchymal transition (EMT) was demonstrated to be the major mechanism responsible for mediating invasiveness and metastasis of late-stage cancers. We therefore investigated the role of NBS1 overexpression in mediating EMT and metastasis. NBS1 overexpression was associated with metastasis of HNSCC patients using tissue microarray-immunohistochemistry approach. Induction of EMT was observed in an NBS1-overexpressing HNSCC cell line (FADUNBS), whereas short-interference RNA (siRNA)-mediated repression of endogenous NBS1 reversed the shift of EMT markers. Increased migration/invasiveness of FADUNBS was shown by in vitro and in vivo assays. NBS1 overexpression upregulated the expression of an EMT regulator Snail and its downstream target matrix metalloproteinase-2. EMT phenotypes and increased migration/invasiveness of FADUNBS cells were reversed by siRNA-mediated repression of Snail expression or a phosphatidylinositol 3-kinase-specific inhibitor. In HNSCC samples, co-expression of NBS1/Snail in primary tumors correlated with metastasis and the worst prognosis. These results indicate that NBS1 overexpression induces EMT through the upregulation of Snail expression, and co-expression of NBS1/Snail predicts metastasis in HNSCCs.

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In Taiwan, hematopoietic SCT (HSCT) has been used to treat patients with hematological diseases since 1983. Since then, more than 2200 patients have undergone HSCT in 15 large hospitals. The disease entities included acute leukemia in 37% of cases, non-Hodgkin's lymphoma in 26%, CML in 10%, multiple myeloma in 7% and severe aplastic anemia in 6%. The conditioning regimens used were mainly myeloablative (84% of cases). Nonmyeloablative regimens were fludarabine-based. The average age of allogeneic recipients was at least 10 years older than those in the era before their application. The grafts of all patients were derived from peripheral blood in 85% of cases, BM in 13% and cord blood (CB) in 2%. Forty percent of HSCT patients received autologous grafts, whereas more than 25% of allogeneic HSCT patients received grafts from unrelated donors, and overall, there were more than 200 Taiwan HSCT recipients. Currently, CB has been used successfully in pediatric patients with thalassemia major and also in adult patients with hematological malignancy. After transplantation, there was a relatively lower prevalence of acute GVHD. However, a relatively higher proportion of hepatitis B carriers in the recipients had led to a higher incidence of viral reactivation and clinical hepatitis, which was dramatically decreased following lamivudine prophylaxis. In conclusion, HSCT has been successfully adapted to routine clinical care in Taiwan. Several important findings contributing to the progress of HSCT in the past two decades have also been noticed on this island.

Summary:We report a nonmyeloablative allogeneic bone marrow transplant (allo-BMT) from an HLA-matched unrelated donor in a case of acute myeloid leukemia (AML), M2 with t(8;21)(q22;q22) and the presence of orbital granulocytic sarcoma (GS), who had residual tumor after conventional chemotherapy. The course of BMT was well tolerated, with no major procedure-related toxicity. The residual orbital GS regressed completely 4 months after BMT. She is currently 19 months post BMT, diseasefree. To our knowledge, this is the first reported pediatric patient with AML, GS and t(8;21)(q22;q22) who received a nonmyeloablative allo-BMT.

There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.