High-dose methotrexate (Hd-MTX) therapy has recently been applied to the treatment of adult acute lymphoblastic leukemia (ALL) based on pediatric protocols; however, its effectiveness for adult ALL ...has not yet been confirmed in a rigorous manner. We herein conducted a randomized phase III trial comparing Hd-MTX therapy with intermediate-dose (Id)-MTX therapy. This study was registered at UMIN-CTR (ID: C000000063). Philadelphia chromosome (Ph)-negative ALL patients aged between 25 and 64 years of age were enrolled. Patients who achieved complete remission (CR) were randomly assigned to receive therapy containing Hd-MTX (3 g/m
) or Id-MTX (0.5 g/m
). A total of 360 patients were enrolled. The CR rate was 86%. A total of 115 and 114 patients were assigned to the Hd-MTX and Id-MTX groups, respectively. The estimated 5-year disease-free survival rate of the Hd-MTX group was 58%, which was significantly better than that of the Id-MTX group at 32% (P=0.0218). The frequencies of severe adverse events were not significantly different. We herein demonstrated the effectiveness and safety of Hd-MTX therapy for adult Ph-negative ALL. Our results provide a strong rationale for protocols containing Hd-MTX therapy being applied to the treatment of adult ALL.
Systemic chemotherapy has shown a significant survival benefit in patients with hepatocellular carcinoma (HCC). However, it is associated with various immune-related adverse events (irAEs). We report ...a case with grade 3 diarrhea and grade 2 colitis following systemic chemotherapy, successfully treated with prednisolone. An 89-year-old man was incidentally detected with a 140-mm hypervascular intrahepatic nodule on contrast-enhanced computed tomography (CECT). Washout of the contrast medium was also detected, and protein induced by vitamin K deficiency or antagonists-II (PIVKA-II) was elevated. Since the Albumin-Bilirubin (ALBI) grade was 2a without any distant metastasis, transarterial chemoembolization (TACE) was performed to treat the HCC, but several intrahepatic nodules were seen in both lobes. Therefore, the patient was treated with lenvatinib for 1 year and 4 months. A complete response according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria was achieved in 2 months; however, multiple hypervascular nodules were detected again. Since the ALBI grade was 1, a second round of chemotherapy with atezolizumab and bevacizumab was initiated. Although a complete response was achieved, the therapy was discontinued due to grade 3 diarrhea and grade 2 colitis after the sixth course. Based on the stool analysis and culture, CECT, and colonoscopy, the diagnosis was atezolizumab-associated colitis. Diarrhea was controlled following the oral administration of 0.5 mg/ kg/day of prednisolone, and atezolizumab-bevacizumab therapy was successfully reinitiated without recurrence of colitis. The management of irAEs is important for a significant survival benefit. Systemic chemotherapy with atezolizumab and bevacizumab can be resumed despite a grade 3 irAE due to atezolizumab. Keywords: hepatocellular carcinoma, immune checkpoint inhibitors, immune-related adverse events, ICI-mediated colitis, IL-17, PIVKA-II
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•Conductance of 1,4-benzenedicarbothioamide (BDTA) molecule has been measured.•BDTA shows a high conductance comparable with that of π-conjugated molecules.•Au/BDTA/Au junctions are ...found to take a few different conductance states.•Geometry and Kohn–Sham orbitals of BDTA have been determined.
We studied the conductance of Au/1,4-benzenedicarbothioamide (BDTA)/Au junctions at room temperature and measured a single-molecule conductance of BDTA. A carbothioamide (thioamide, –CSNH2) group of this molecule consists of two potential linkers, thioketone and amine groups, and would thus be expected to show high conductance. The experimental single-molecule conductance of BDTA is (0.8–1.0)×10-3G0 which roughly compares with that of π-conjugated molecules. We consider that this relatively high conductance of Au/BDTA/Au is due to the homoconjugation of π-orbitals of benzene and sulfur while the amine group is likely to remain as a side group. We also observed that Au/BDTA/Au junctions can exist in multiple configurations of different conductances.
The weak classical through-space magnetic dipolar interactions have, in general, not been an important component in stabilizing bulk magnets, as the strong quantum-mechanical through-bond exchange ...couplings dominate. We show that for materials composed of strongly exchange-coupled magnetic chains with very weak interchain exchange, the interchain dipolar interactions may dominate, leading to sizable ordering temperatures. The single-ion anisotropy together with the anisotropy of the dipole interaction determine the magnetic ordering directions. The family of Mn(porphyrin)+cyanocarbon- magnets is shown to order due to classical interchain dipolar interaction in combination with the single-ion anisotropy, resulting in canted magnetic structures.
Transport and ESR measurements have been performed on organic semiconductors synthesized by the diffusion method. For (BEDT-TTF)Cu
2Br
4, a pressure of 1
GPa raises the conductivity by up to one ...order of magnitude, but does not alter the semiconducting nature. By the ESR measurements, we find no Cu
2+ signals, indicating that the BEDT-TTF molecules are divalent. The Hall carrier concentration increases exponentially with temperature, approaching the spin concentration evaluated by the low-temperature ESR from
π-electrons. Thermopower measurements also support the contribution of the thermally activated electronic carriers. For (BEDTTTF)
2Cu
3Br
7(H
2O), the conductivity increases twice by applying a pressure of 0.8
GPa.
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