Rituximab is recognized as a useful drug for the treatment of B-cell non-Hodgkin's lymphoma and its use has been extended to such diseases as idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, chronic rheumatoid arthritis and AN-CA-associated vasculitides. One serious complication associated with its use is the reactivation of hepatitis B virus and the search for methods to prevent this occurrence has resulted in the rapid accumulation of knowledge. In this review, we discuss case analyses from our department and other groups and outline the current knowledge on the topic and the remaining issues.© 2013 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Rituximab; Hepatitis B virus; Reactivation; Chemotherapy; Lamivudine; Non-Hodgkin's lymphoma Core tip: The deleterious effects of hepatitis B virus (HBV) reactivation in rituximab-containing chemotherapy regimens have been reported and the effect of lamivudine treatment in the prevention of HBV reactivation is also well documented. Once reactivated, HBV may lead to death due to hepatitis. In this review, we discuss the factors of preventive lamivudine treatment (especially in the course of HBV antibody), including to whom and for how long the drug should be given, based on case studies and reports that span rituximab's debut in 2002 on the Japanese market to June 2013.

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Background Comprehensive cancer genomic profiling has been used recently for patients with advanced solid cancers. Two cancer genomic profiling tests for patients with no standard treatment are covered by Japanese public health insurance since June 2019. Methods We prospectively analyzed data of 189 patients with solid cancers who underwent either of the two-cancer genomic profiling tests at Hokkaido University Hospital and its liaison hospitals and whose results were discussed in molecular tumor board at Hokkaido University Hospital between August 2019 and July 2020. Results All 189 patients had appropriate results. Actionable gene alterations were identified in 93 patients (49%). Frequent mutations included PIK3CA (12%) mutation, BRCA1/2 alteration (7%), ERBB2 amplification (6%) and tumor mutation burden-High (4%). The median turnaround time from sample shipping to acquisition by the expert panel was 26 days. Although 115 patients (61%) were provided with information for genotype-matched therapies, only 21 (11%) received them. Notably, four of eight patients below the age of 20 years were provided information for genotype-matched therapies, and three received them. Their response rates and disease control rates were 29% and 67%, respectively. Most patients who did not undergo the genotype-matched therapies were provided information for only investigational drugs in phases I and II at distant clinical trial sites in central Japan. Twenty-six patients were informed of suspected germline findings, while 11 patients (42%) received genetic counseling. Conclusions The publicly reimbursed cancer genomic profilings may lead to the modest but favorable therapeutic efficacy of genotype-matched therapy for solid cancer patients with no standard therapy. However, poor access to genotype-matched therapy needs to be resolved.

In our prior study it was demonstrated that residues 46 and 54 on a synthetic peptide, AEGFSYTVANKNKGIT (50V), work as an agretope (site contacts with major histocompatibility complex molecules) and residues 50 and 52 function as an epitope (site contacts with T cell receptor), when tri-molecular complexes are formed among 50V,I-Ab and the T cell receptor. 50V was composed of residues 43 to 58 of pigeon cytochrome c (p43-58) except that the aspartic acid (D) at residue 50 was substituted by valine (V). Substitution of agretopic residues on 50V changed this I-Ab-binding peptide to an I-Ak-binding peptide, suggesting that positions 46 and 54 work as an agretope in I-Ak-restricted T cell responses. In the present study we examined whether residues 46 and 54 of 50V worked as agretopes in T cell responses restricted to other I-A haplotypes. The 50V-related peptides with phenylalanine (F) at position 46 and alanine (A) at position 54 bound tightly to I-Ab, I-Ad, I-Aq and I-As molecules and stimulated T cells most potently in mice bearing these I-A haplotypes. In contrast, 50V-related peptides carrying D at position 46 and A at position 54 bound most potently to I-Ak molecules, and the peptides with arginine (R) at position 46 and A at position 54 bound most efficiently to I-Av molecules. The present findings, thus, demonstrate that the agretopic positions on the p43-58 related peptides are preserved in T cell responses restricted to each I-A haplotype studied, and that the specific amino acids on the agretopic positions exist a priori for each I-A allele-specific structure.