Suppression of angiotensin converting enzyme 2, a host receptor for SARS-CoV-2 infection, using 5-aminolevulinic acid in vitro.

Angiotensin converting enzyme 2 (ACE2), an entry receptor found on the surface of host cells, is believed to be detrimental to the infectious capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Scientists have been working on finding a cure since its outbreak with limited success. In this study, we evaluated the potential of 5-aminolevulinic acid hydrochloride (ALA) in suppressing ACE2 expression of host cells. ACE2 expression and the production of intracellular porphyrins following ALA administration were carried out. We observed the reduction of ACE2 expression and intracellular porphyrins following ALA administration. ALA suppressed the ACE2 expression in host cells which might prevent binding of SARS-CoV-2 to host cells. Co-administration of ALA and sodium ferrous citrate (SFC) resulted in a further decrease in ACE2 expression and increase in intracellular heme level. This suggests that the suppression of ACE2 expression by ALA might occur through heme production. We found that the inhibition of heme oxygenase-1 (HO-1), which is involved in heme degradation, also resulted in decrease in ACE2 expression, suggesting a potential role of HO-1 in suppressing ACE2 as well. In conclusion, we speculate that ALA, together with SFC administration, might serve as a potential therapeutic approach in reducing SARS-CoV-2 infectivity through suppression of ACE2 expression.

Infusion Rate Escalation Study of Rituximab in Patients with CD20+ B-Cell Lymphomas: A Single Institution Analysis in Japan.

Background. To determine the maximum tolerable infusion rate of rituximab, and investigate the safety and feasibility of rapid infusion of rituximab for patients with CD20 positive B-cell lymphomas (CD20+NHL). Patients and Methods. 18 patients with CD20+NHL were registered. This study had six cohorts of administration rate of rituximab. The median age was 56 years (range, 38-79), and five of 18 patients were male. Two patients (11%) with diffuse large B-cell lymphoma were receiving R-CHOP therapy, two (11%) with indolent lymphoma were receiving R-CVP therapy, and 14 (78%) with indolent lymphoma were receiving rituximab as maintenance therapy. Results. A total of 88 cycles of rituximab was administered. Rapid infusion of rituximab was well tolerated, with only one grade 3 leukocytepenia and one grade 4 neutropenia. Four patients (22%) developed grade 1 infusion-related toxicities at the first administration of rituximab. No patient with severe drug-related events was observed. Conclusions. We determined that the maximum tolerable infusion rate of rituximab is 300 mL/h (under 700 mg/h), and confirmed that administration of over 60 minutes is safe and feasible. We recommend rapid administration of rituximab for practice setting in patients with CD20+NHL being treated with rituximab or rituximab-containing chemotherapy. (Clinical trial no. JFCR2009-1027).

R-CHOP with dose-attenuated radiation therapy could induce good prognosis in gastric diffuse large B cell lymphoma.

BACKGROUND: The treatment strategy for gastric diffuse large cell lymphoma (DLBCL) has not been standardized in such as to the cycles of chemotherapy, dose of radiation, or necessity for the surgery. Although the results of CHOP or R-CHOP treatments have demonstrated the good prognosis, the treatments have been controversial in many cases. METHODS: We retrospectively analyzed 40 gastric DLBCL patients receiving chemotherapy with or without radiation in our institute. Those in stages II-IV were treated with six cycles of R-CHOP without radiation; for those in stage I, we administered three cycles of R-CHOP with radiation. RESULTS: The three-year overall survival (OS) and progression-free survival (PFS) rates were 95.2 and 91.8%, respectively. Those in stage I obtained 100% of OS. The radiation dose prescribed was 30.6 Gy for CR cases and 39.6 to 40 Gy for PR after chemotherapy. Although survival rates tended to correlate with staging groups or age-adjusted IPI classifications, multivariate statistical analysis did not show clear differences. All 14 patients with initial bleeding were successfully managed without surgery during treatment. CONCLUSION: R-CHOP therapy was very effective for gastric DLBCL. It may be not necessary to use more than 30.6 Gy of radiotherapy in the highly chemo-sensitive cases. Less toxic treatments should be made available to gastric DLBCL patients.

High thymidine kinase activity is a strong predictive factor for poor prognosis in peripheral T-cell lymphoma treated with cyclophosphamide, adriamycin, vincristine and prednisone.

The prognosis of patients with peripheral T-cell lymphoma (PTCL) treated with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP) is poor, but their laboratory prognostic parameters had not previously been evaluated. We retrospectively reviewed 55 patients with newly diagnosed PTCL treated with CHOP from August 1999 to May 2009 at our institution. We analyzed six laboratory parameters, including thymidine kinase (TK) activity, to evaluate overall survival, which was the primary end-point. In multivariate analysis, the overall survival was significantly worse in patients with high TK activity (hazard ratio 34.8, 95% confidence interval [CI] 1.03-1176.23). The overall response rate among patients with high TK activity was 21.4%, significantly poorer compared with other parameters (p = 0.001). High TK activity predicts poor overall survival among patients with newly diagnosed PTCL treated with CHOP. Response to CHOP treatment is significantly decreased in patients with PTCL with high TK activity.