Non-primate hepacivirus (NPHV) is recently identified as a closely related homologue of hepatitis C virus. The previous studies showed a high prevalence of NPHV infection among Japanese domestic horses originated from abroad. The historical distribution of NPHV among horses in Japan, therefore, is still unknown. In this study, seroepidemiological study of NPHV was conducted using 335 sera from five breeds of Japanese native horses. These horses are maintained as the pedigree and are reared apart from other horse breeds. The detection of antibodies against NPHV were conducted by western blot analysis using the recombinant protein of the NPHV core protein. The antibodies against NPHV were detected in all five breeds, 83 out of 335 (23.4%) horses. These results suggested that NPHV was circulating among Japanese native horses.
We present the case of a 78-year-old male patient who was diagnosed with anaplastic lymphoma kinase (ALK)-negative, CC chemokine receptor 4 (CCR4)-negative, and CD30-positive anaplastic large cell lymphoma (ALCL). The patient had a past medical history of adult T-cell leukemia/lymphoma and colon cancers that had developed simultaneously approximately 2 years prior to the development of ALCL that were treated with immunochemotherapy and resection, respectively. Initial treatment for ALCL included brentuximab vedotin, an anti-CD30 monoclonal antibody-monomethyl auristatin E conjugate; however, we were unable to achieve a sufficient treatment effect. Romidepsin, an oral histone deacetylase inhibitor, was introduced as salvage chemotherapy; complete remission was attained. Interestingly, a reversal of the CD4/CD8 ratio and a reduction in human T-lymphotropic virus type 1 (HTLV-1) virus load was observed after 2 cycles of immunochemotherapy; the patient experienced upregulation of HTLV-1 Tax-specific cytotoxic T lymphocytes after a herpes zoster infection and the completion of immunotherapy. The immunologic status was maintained from the time of diagnosis through the completion of romidepsin therapy. Our findings indicate that romidepsin can be used safely and effectively to treat ALCL without impairing cellular immunity to HTLV-1.
Porcine circovirus associated diseases (PCVAD) have multiple manifestations that have been attributed to porcine circovirus type 2 (PCV2). Recently, a novel porcine circovirus, PCV type 3 (PCV3), was identified in pigs with systemic inflammation of unknown etiology. In this study, we tried to detect the PCV3 genome in tissue samples collected from Japanese pig herds in 2016. The PCV3 genome was detected by PCR in 7 of 73 samples. The homology between each Japanese strain was 99.5% for the full-length sequence and 98.9 to 99.2% for the open reading frame 2. These results suggest that PCV3 has already invaded Japanese pig farms.
Vascular dementia (VaD) is the second common cause of dementia after Alzheimer's disease, and deep learning has emerged as a critical tool in dementia research. The aim of this article is to highlight the current deep learning applications in VaD-related imaging biomarkers and diagnosis.
This case report is about a patient who suffered from Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia. The blasts were positive for myeloid-lineage markers including CD13 and CD33, as well as B-cell-lineage markers. Minor <i>bcr-abl1</i> mRNA was detected by real-time quantitative polymerase chain reaction. Chromosomal abnormality monosomy 7 was also observed, in addition to Ph1. Despite treatment difficulties that were anticipated based on these findings, the patient had long-time complete molecular response (CMR) for approximately 5 years using chemotherapy and two tyrosine kinase inhibitors, imatinib and dasatinib. Lymphocytes were elevated after the patient switched from imatinib to dasatinib, and a T-cell receptor (TCR) <i>V beta</i> gene repertoire analysis revealed oligoclonal expansion of effector and memory cytotoxic T lymphocytes (CTLs), including Wilms tumor 1-specific CTLs. More specifically, the two memory CTLs expressing TCR <i>V beta 3</i> and <i>V beta 7.1</i> gradually increased after dasatinib administration. The activation and maintenance of anti-leukemia immunity may have allowed the patient to obtain long-time CMR. These results highlight that obtaining memory CTLs for leukemia cells may lead to safe withdrawal from dasatinib in the patient.
Background/Aim: Adult T-cell leukemia/lymphoma (ATLL) is a relatively refractory CD4-positive peripheral T-cell lymphoma. VCAP-AMP-VECP (mLSG15) is one of the standard chemotherapeutic regimens for patients with aggressive ATLL. Mogamulizumab (moga), a monoclonal antibody for C-C chemokine receptor 4 antigen expressed on the cell surface, has recently been poised for use as monotherapy and in combination with chemotherapy. However, to date, a significant survival benefit has not been obtained with the combination of moga + mLSG15 therapy. Patients and Methods: We retrospectively analyzed 77 patients diagnosed with aggressive ATLL. Of them, 22 were treated with moga + a chemotherapy regimen comprised of etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisolone (EPOCH), 16 with moga + mLSG15, and 39 with chemotherapy alone. Results: A risk reduction of approximately 30% was obtained with moga + EPOCH compared with moga + mLSG15. Conclusion: The addition of moga to chemotherapy did not result in a survival benefit compared with chemotherapy alone. However, a statistically significant overall survival benefit was observed in patients with moga-induced skin disorders.
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib are primarily used in the initial treatment of chronic phase (CP)-chronic myeloid leukemia (CML), as CMLs harbor the BCR-ABL fusion product. An increased number of lymphocytes and large granular lymphocytes (LGLs) have been observed in patients treated with dasatinib, but not other TKIs. The LGLs have been reported to be primarily natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In the present study, a CP-CML patient who has maintained molecular response 5 for >2.4 years after stopping dasatinib was reported. Memory and effector CTLs and NK cells, were observed after 2.4 years of treatment-free remission, despite the fact that lymphocyte counts are not elevated in the patient. These results suggest that dasatinib may induce cellular immunity, including NK cells and CTLs and this cellular immunity may be maintained for a long period following cessation of dasatinib. The results suggest that this cellular immunity may provide a long-term cure without the need for continued TKI treatment.
Herein, we present the case of a patient who suffered from adult T-cell leukemia/lymphoma (ATLL) and hepatocellular carcinoma (HCC) after obtaining a sustained virological response following treatment with a direct-acting antiviral (DAA) at different points in time. The patient went into complete remission (CR) for ATLL. Unfortunately, subsequent relapse of ATLL was observed. This situation was overcome using chemotherapy with pegylated interferon alpha-2b. Human T lymphotropic virus type 1 Tax-specific cytotoxic T lymphocytes (CTLs) were recognized after obtaining second CR, and those CTLs have been maintained for many years. After 4 years from the second CR, chronic hepatitis type C was treated with a DAA, and sustained virological response was attained. However, the occurrence of HCC was detected. Surprisingly, the tumor disappeared spontaneously. Hepatitis virus type C-specific CTLs were also detected in the patient. T-cell receptor (TCR) V beta gene repertoire analyses revealed oligoclonal expansion of effector and memory CTLs. The number of CTLs expressing the TCR V beta 13.1 has increased over the years since HCC occurrence. The activation and maintenance of anticancer cellular immunity may have allowed the patient to obtain long-term survival and overcome two lethal neoplasms.
Background: Generation of BCR‐ABL fusion gene by reciprocal translocation of chromosomes 9 and 22 immortalizes hematopoietic stem cells, thereby leading to chronic myeloid leukemia (CML). Significant improvement in the prognosis of CML has been achieved since the introduction of tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib and nilotinib. However, to date, no consensus about the cessation of TKIs in CP‐CML patients has been obtained. We recently reported the case of a CP‐CML patient with long‐term complete molecular response (MR) after cessation of dasatinib, who has been maintaining memory cytotoxic T lymphocytes (CTLs) with T cell receptor (TCR) clonality (Jo et al. Oncology Letters 15: 2935‐2938, 2018). [A1]Abbreviations should be introduced at the first occurrence of the term. Aims: We planned to examine effector and memory CTLs in CP‐CML patients treated with TKIs. We also investigated CML specific cellular immune response. Methods: We examined the TCR Vb gene repertoire to analyze TCR clonality of CD8‐positive T cells in CP‐CML patients treated with TKIs using flow cytometry. We defined a TCR Vb gene percentage of 10% and above as being positive for monoclonality in this study. Tumor antigen specific CTLs were also analyzed using WT1‐, human TERT‐, and PR‐1‐tetramers by flow cytometry in CP‐CML patients having HLA‐A∗02:01:01/02:06:01 and/or HLA‐A∗24:02 treated with dasatinib. Results: We analyzed 15 patients treated with TKIs including dasatinib (Dasa group) and 8 patients treated with TKIs without dasatinib (non‐Dasa group). No significant statistical difference was observed in the median age at first TKI administration, the MR at the time of TCR clonality assay, and the NK cell percentages between the 2 groups. The time of TCR clonality assay was significantly earlier in tghe Dasa group than in the non‐Dasa group (P = 0.0013). Approximately 73% and 87% positivity of effector and memory CTL clonality was observed in the Dasa group; while approximately 38% and 50% positivity of effector and memory CTL clonality was observed in the non‐Dasa group, although the TKI exposure time for this group was significantly longer. Notably, the positive percentages of effector and memory CTL clonality in the non‐Dasa group are quite similar to the overall probabilities of maintenance of deep MR reported in various imatinib‐stop studies such as the STIM study (Mahon et al. Lancet Oncol 11: 1029‐1035, 2010) and the TWISTER study (Ross et al. Blood 122: 515‐522, 2013). Table 1 summarizes the data of TCR clonality and tetramer analyses in CP‐CML patients having HLA‐A∗02:01:01/02:06:01 or A∗24:02 treated with dasatinib. Patient‐4 has both HLA‐A∗02:01:01 and A∗24:02. Effector and/or memory CTL clonality was observed in all patients except for Patient‐5. TCR Vb2 and Vb14 genes were predominantly observed in patients having A∗02:01:01/02:06:01; while TCR Vb1 , Vb2 , and Vb9 genes were predominantly observed in patients having A∗24:02. Tetramer assays showed that tumor specific CTLs were positive in 2 patients (50%) having A∗02:01:01/02:06:01 and 4 patients (80%) having A∗24:02. Summary/Conclusion: Effector and memory CTL clonality was attained more rapidly and frequently in dasatinib‐treated CP‐CML patients than in patients treated with TKIs without dasatinib. The positive percentages of CTL clonality resembled the percentages of TFR in various TKI‐stop studies. These results suggest that the acquisition of CTL clonality may provide long‐term remission and TFR to CP‐CML patients and that cessation of TKIs should be considered in patients with clonal expansion of memory CTLs. image
