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Allogenic hematopoietic stem cell transplantation (allo-HSCT) is not a standard therapy for solid cancer because of its high toxicity and insufficient evidence levels. However, the potential graft-versus-solid-tumor (GVT) effect of this therapy has been discussed. Many case reports have also described treatment effects of allo-HSCT in patients with hematologic malignancies and active solid tumors. A 38-year-old woman treated with fulvestrant and abemaciclib for recurrent breast cancer with multiple lung metastases was diagnosed with myelodysplastic syndrome (MDS) with increased blasts 2. She was classified as adverse risk by the 2017 European LeukemiaNet risk stratification and as very high risk by the Molecular International Prognostic Scoring System. Breast cancer treatment was interrupted and venetoclax and azacitidine therapy was started. Complete hematologic response was achieved after three cycles. However, multiple lung metastases from the breast cancer remained. The patient then underwent umbilical cord blood transplantation. She has maintained complete remission of MDS as of 1 year post-transplantation, without serious complications. Lung metastatic activity on FDG-PET/CT scan also completely disappeared by half a year post-transplantation, and this response has continued as of 1 year post-transplantation. This favorable treatment course suggests the existence of a GVT effect. [ABSTRACT FROM AUTHOR]

Iron is an essential trace metal, vital for various physiologic processes, but excess levels can harm health. Maintaining iron homeostasis is critical, with hepcidin playing a key role. The isoform hepcidin-25 exerts the most significant influence on iron metabolism, making its serum levels a valuable diagnostic tool. However, mass-spectrometry and other conventional measurement methods can be difficult to perform, and some immunoassays lack reliability. In this study, we employed a recently developed latex agglutination method integrated with a readily available automated analyzer to quantify serum hepcidin-25 levels in both volunteers recruited from personnel of our hospital (n = 93) and patients with various hematological disorders (n = 112). Our findings unveiled a robust positive correlation between serum hepcidin-25 and ferritin, as well as C-reactive protein levels, in both volunteers and patients. Among the patients with hematological disorders, there was a noteworthy negative correlation between hepcidin-25 levels and hemoglobin concentrations, as well as reticulocyte counts. Interestingly, the hepcidin-25/ferritin ratio was remarkably low in patients with hemolytic anemia and myelodysplastic syndromes with ring sideroblasts. Our findings suggest that quantifying serum hepcidin-25 and the hepcidin-25/ferritin ratio using this method may be valuable for screening of hematopoietic diseases and other iron metabolism disorders. [ABSTRACT FROM AUTHOR]

Myeloid sarcoma (MS) in the complete absence of bone marrow disease is an extremely rare phenomenon. We report the case of a 78-year-old woman with multiple subcutaneous lung and liver nodules, including mediastinal and peritoneal lymph node swelling, who had been receiving methotrexate (MTX) for 10 years for rheumatoid arthritis (RA). She was initially diagnosed with ALK-negative anaplastic large cell lymphoma. After one course of an anthracycline-containing regimen, pathologic cells were identified as CD68 (Kp-1)-positive with myeloid-lineage tumor cells and abnormal karyotypes with 8q21 and 21q22. Subsequent treatment was changed to acute myelogenous leukemia (AML) induction chemotherapy. Although the lesions were partially reduced in size following treatment for lymphoma, complete response (CR) was obtained only after AML chemotherapy. The patient remained in CR over 3 years after the last chemotherapy. This case may indicate an association between long-term MTX use and MS. An early diagnosis and adequate therapy may be important for improving survival outcomes in MS. This report demonstrates that CD68 staining is important for the differential diagnosis of MS and lymphoma. Careful follow-up is necessary for this patient, who may be the first case of MS after methotrexate use for RA. [ABSTRACT FROM AUTHOR]

Meningioma is derived from arachnoid cells covering the surface of the brain and spinal cord, and it has characteristics shared by mesothelioma arising from the pleura and peritoneum in that it takes an epithelioid appearance despite its mesenchymal origin. We examined the immunohistochemical expression of podoplanin and calretinin, both of which are well-known markers of mesothelioma, in 24 surgical cases of meningioma of various types. In most cases, a linear immunoreactivity for podoplanin was found along the cell surface of most neoplastic cells. An intracytoplasmic, finely granular, or diffuse immunoreactivity was also noted in some cells. These findings corresponded well to immunoreactivity for epithelial membrane antigen (EMA), but immunoreactivity for podoplanin was more crisp or sharply delineated and clear compared with that for EMA. These findings indicate that podoplanin can be used as an immunohistochemical marker that is equivalent to EMA in the differential diagnosis of meningioma. However, most meningiomas did not contain calretinin-immunoreactive cells, a finding that differs from the diffuse immunoreactivity seen in mesothelioma. [ABSTRACT FROM AUTHOR]

In-cell NMR is an application of solution NMR that enables the investigation of protein conformations inside living cells. We have measured in-cell NMR spectra in oocytes from the African clawed frog Xenopus laevis. 15N-labeled ubiquitin, its derivatives and calmodulin were injected into Xenopus oocytes and two-dimensional 1H–15N correlation spectra of the proteins were obtained. While the spectrum of wild-type ubiquitin in oocytes had rather fewer cross-peaks compared to its in vitro spectrum, ubiquitin derivatives that are presumably unable to bind to ubiquitin-interacting proteins gave a markedly larger number of cross-peaks. This observation suggests that protein–protein interactions between ubiquitin and ubiquitin-interacting proteins may cause NMR signal broadening, and hence spoil the quality of the in-cell HSQC spectra. In addition, we observed the maturation of ubiquitin precursor derivative in living oocytes using the in-cell NMR technique. This process was partly inhibited by pre-addition of ubiquitin aldehyde, a specific inhibitor for ubiquitin C-terminal hydrolase (UCH). Our work demonstrates the potential usefulness of in-cell NMR with Xenopus oocytes for the investigation of protein conformations and functions under intracellular environmental conditions. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATL, especially the acute and lymphoma subtypes, is poor with conventional and high-dose chemotherapy. The effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ATL has been reported, suggesting the presence of a graft-versus-leukemia (GVL) effect against this malignancy. To identify the target antigens associated with tumor rejection, we used SEREX (serological identification of antigens by recombinant cDNA expression cloning) to screen ATL complementary DNA expression libraries with sera from an ATL patient who had a GVL response after allo-HSCT. Among the isolated clones, autocrine motility factor receptor (AMFR), which encodes a glycosylated transmembrane protein, was found to have selective reactivity with the sera obtained during tumor regression. Real-time reverse transcription polymerase chain reaction analysis for AMFR showed highest expression in the testis among normal tissues. Furthermore, aberrant AMFR expression was found in at least some ATL patients. Taken together, these findings suggest that AMFR may be one of the GVL antigens that provoke effective antitumor immunity against ATL in allogeneic settings. [ABSTRACT FROM AUTHOR]