Daratumumab in first-line therapy is cost-effective in transplant-eligible patients with newly diagnosed myeloma.

Triplet regimens, such as lenalidomide, bortezomib, and dexamethasone (RVd) or thalidomide, bortezomib, and dexamethasone (VTd), are standard induction therapies for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The addition of daratumumab to RVd and VTd has been investigated in the GRIFFIN and CASSIOPEIA trials, respectively, resulting in improvement in the rate of minimal residual disease (MRD) negativity. In this study, we conducted a cost-effectiveness analysis with a 10-year time horizon to compare first-line and second-line use of daratumumab for transplant-eligible patients with NDMM. Because long-term follow-up data for these clinical trials are not yet available, we developed a Markov model that uses MRD status to predict progression-free survival. Daratumumab was used either in the first-line setting in combination with RVd or VTd or in the second-line setting with carfilzomib plus dexamethasone (Kd). Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were calculated from a Japanese and US payer perspective. In the Japanese analysis, D-RVd showed higher QALYs (5.43 vs 5.18) and lower costs (¥64 479,793 vs ¥71 287 569) compared with RVd, and D-VTd showed higher QALYs (5.67 vs 5.42) and lower costs (¥43 600 310 vs ¥49 471,941) compared with VTd. Similarly, the US analysis demonstrated dominance of a strategy incorporating daratumumab in first-line treatment regimens. Given that overall costs are reduced and outcomes are improved when daratumumab is used as part of a first-line regimen, the economic analysis indicates that addition of daratumumab to first-line RVd and VTd regimens is a dominant strategy compared with reserving its use for the second-line setting.

Increased trough concentration of venetoclax when combined with itraconazole for acute myeloid leukemia.

The administration of venetoclax (Ven) with azacitidine (Aza) was used as induction or salvage therapy for 34 patients with acute myeloid leukemia (AML) in our institute. An itraconazole oral solution (ITCZ-OS) was administered to 17 patients (50%) as antifungal prophylaxis. The trough concentration of Ven was significantly higher in patients treated with ITCZ than in those who were not (median values, 1.31 µg/mL vs. 0.64 µg/mL; p = 0.0072). Ven concentrations were > 3 µg/mL in some patients treated with ITCZ and the patient with the highest Ven concentration (5.58 µg/mL) expired after grade 4 neutropenia persisted for more than 50 days after the 1st cycle of Ven/Aza. It was also found that the group with concentrations equal to or above 1.29 µg/mL showed a significantly higher rate of achieving CR or CRi (p = 0.039). In conclusion, the measurement of Ven concentrations in AML cases is essential in daily clinical practice, particularly in those receiving antifungal prophylaxis.

[Diffuse large B-cell lymphoma concurrent with Kaposi's sarcoma in the same lymph node in a human immunodeficiency virus-negative patient].

An 80-year-old Japanese man presented with systemic lymphadenopathy, including the para-aortic area and left inguinal nodes, which was diagnosed as diffuse large B-cell lymphoma (DLBCL) and human herpesvirus (HHV) 8-positive/HIV-negative Kaposi's sarcoma (KS). Immunohistochemical examination revealed that the lymphoma cells were negative for HHV-8. The patient received combined chemotherapy with rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone for six cycles and achieved complete remission. In the literature, five cases of simultaneous appearance of malignant lymphoma and KS in the same lymph node have been reported, but DLBCL as a histological subtype has not yet been reported.

[Analysis of anti-SARS-CoV-2 IgG antibody titers after mRNA booster vaccination in patients with nonmalignant hematological disorders].

In our facility, anti-SARS-CoV-2 mRNA vaccines were given to 21 patients, including 8 with aplastic anemia (AA), 3 with pure red cell aplasia (PRCA), and 10 with immune thrombocytopenic purpura (ITP), and IgG antibody titers were assessed one month after vaccinations. After receiving both a second vaccine and a booster shot, all patients with AA/PRCA treated with cyclosporine A aside from one, had IgG titers that were lower than the median levels of healthy controls. Even if prednisolone (PSL) doses did not go over 10 mg/day, ITP patients receiving PSL therapy were unable to achieve adequate levels of IgG after booster immunizations.

[Outcomes of COVID-19 due to omicron variant infection complicated with hematological disorders].

When the omicron variant became the most dominant severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) variant causing coronavirus disease 2019 (COVID-19) in Japan, 11 patients with hematological diseases infected with this new variant were treated at our institution. Among them, four of the five patients who had been treated with chemotherapy progressed to moderate-II COVID-19, and two of them died. In contrast, five of the six patients who did not receive the treatment remained at mild to moderate-I stage of COVID-19, except for a single case progressing to moderate-II COVID-19. While all four patients infused with anti-coronavirus monoclonal antibodies within 8 days after the onset survived, the other two patients, being withheld from treatment or treated later, died. In these two cases, anti-SARS-Cov-2 immunoglobulin G antibodies remained at low titers. Although the omicron variant is considered a less harmful SARS-Cov-2 variant, patients with hematological disorders, particularly those who are immunosuppressed caused by chemotherapy, should be continuously cared for as they remain at a higher risk of severe COVID-19 due to insufficient or delayed anti-viral humoral immunity development. Thus, the rapid introduction of antiviral monoclonal antibodies together with anti-viral reagents may rescue these patients.

Clinical interaction between dexamethasone and aprepitant in chemotherapy for lymphoma.

Aprepitant (Apr) is an effective antiemetic agent for chemotherapy-induced nausea and vomiting (CINV). Current CINV guidelines recommend the antiemetic combination of a 5-HT3 receptor antagonist, Apr, and dexamethasone (Dex) for highly emetogenic chemotherapies. Apr inhibits CYP3A4 dose-dependently. Since Dex is metabolized by CYP3A4, the combined use of Apr and Dex inhibits Dex metabolism. CINV guidelines therefore recommend dose-reduction of Dex when Apr and Dex are used together. However, there is some controversy over whether or not Dex should be reduced when administered as an antitumor agent for lymphoid malignancies. We retrospectively compared the antitumor effect of Dex-containing chemotherapy in which Dex is administered at the usual dose without Apr (group A) or administered at a half-dose in combination with Apr (group B). We analyzed 62 consecutive patients with refractory or relapsed CD20 + B cell lymphoma who received R-DHAP therapy in our hospital, including 29 and 33 cases in groups A and B, respectively. The response rate at the end of the first course of R-DHAP was 62.1% and 54.5%, respectively (P = 0.61). As another endpoint to evaluate the effect of Dex, group B tended to show greater suppression of the lymphocyte count (P = 0.05). Therefore, decreasing the dose of Dex by half appeared to be reasonable when combined with Apr.

Clinical association between thyroid disease and immune thrombocytopenia.

Immune thrombocytopenia (ITP) can coexist with autoimmune thyroid disease. However, the detailed clinical features remain unknown. We retrospectively reviewed 248 patients with newly diagnosed ITP in our institute for whom we had thyroid function data at diagnosis between 2000 and 2019. Of the 248 patients with ITP, 74 patients also had thyroid disease, including 36 with overt thyroid disease (13 Graves' disease and 23 Hashimoto's thyroiditis) and 38 with subclinical thyroid disease (3 hyperthyroidism and 35 hypothyroidism). ITP and thyroid disease were concurrently diagnosed in 54 patients. Female sex and positivity for antinuclear antibodies (ANA) were significantly associated with thyroid diseases. Platelet-associated immunoglobulin G (PAIgG) levels in patients with Graves' disease were higher than those in patients with Hashimoto's thyroiditis. Platelet counts were similar among euthyroid patients and patients with thyroid disease. Thrombopoietin-receptor agonist was administered more frequently in patients with thyroid disease. The cumulative incidences of thrombosis and bleeding and overall survival did not differ between patients with and without thyroid disease. Treatment for thyroid disease in 22 patients improved thrombocytopenia in 21 patients, especially in 4 patients who were not treated for ITP. This study demonstrated that thyroid diseases were commonly found in patients with ITP. Treatment of the underlying thyroid disease may improve thrombocytopenia.

Evaluation of thrombotic events in patients with immune thrombocytopenia.

Immune thrombocytopenia (ITP) has been reported to be associated with thrombotic events. The incidence of thrombosis in 303 newly diagnosed ITP patients in our institute between 2000 and 2016 was retrospectively reviewed. During a median follow-up of 3.6 years, 16 thrombotic events (12 arterial and four venous) occurred. The median platelet count at thrombotic events was 102 × 109/l. At 10 years, the cumulative thrombosis incidence was 10%. A univariate analysis showed that smoking, hypertension, male gender, a history of thrombosis, and atrial fibrillation (Af) were significantly associated with the occurrence of thrombosis, and a multivariate analysis identified smoking and Af as independent risk factors. The thrombotic risk was not increased by lupus anticoagulant positivity or ITP treatment. At 5 years, the cumulative incidence of bleeding and overall survival probability was 5.6% and 92%, respectively. This study demonstrates that smoking and Af were associated with an increased risk of thrombosis. Previously identified risk factors were not confirmed in these Japanese ITP patients.

Factors that predict delayed platelet recovery after autologous stem cell transplantation for lymphoma or myeloma.

The amount of infused CD34+ cells has been reported to be the strongest predictor of platelet recovery after autologous stem cell transplantation (ASCT). However, the timing of platelet recovery varies widely among patients even after the infusion of similar amounts of CD34+ cells. Therefore, we retrospectively assessed 99 patients who underwent their first ASCT for lymphoma or myeloma at our center. Thirteen patients (13%) did not achieve platelet engraftment, defined as a platelet count of at least 2.0 × 104/µL without transfusion, at day 28 after transplantation, whereas 58 of 60 patients (97%) who received at least 2.0 × 106/kg CD34+ cells achieved platelet engraftment within 28 days. Multivariate analysis identified the following significant risk factors for delayed platelet recovery: hemoglobin level and platelet count before stem cell harvest, body temperature of > 39 °C within 5 days after ASCT, and infusion of a small amount (< 2.0 × 106/kg) of CD34+ cells. In a subgroup analysis of 39 patients infused with < 2.0 × 106/kg CD34+ cells, a need for repeated apheresis for stem cell harvest and a body temperature of > 39 °C within 5 days after ASCT were identified as independent factors for delayed platelet recovery. In summary, platelet recovery following ASCT was affected by insufficient hematopoietic recovery at stem cell harvest, a need for repeated apheresis, and high fever early after ASCT, particularly when the amount of infused stem cells was insufficient.

Steep neutrophil recovery following unrelated bone marrow transplantation is a major risk factor for the development of acute graft-vs-host disease-a retrospective study.

The speed of neutrophil recovery following allogeneic hematopoietic cell transplantation (allo-HCT) varies widely among patients. We retrospectively evaluated the slope of neutrophil recovery (N slope) in 120 patients who underwent a first unrelated bone marrow transplantation with granulocyte-colony-stimulating factor support between 2009 and 2018. The median N slope was 205.5/µl/day. We classified patients into low (n = 59) and high (n = 61) N slope groups with a cutoff value of 200/µl/day. The high N slope group correlated with older patients, RIC regimen, high CD34+ cells, and recent transplantation. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was significantly higher in the high N slope group than in the low N slope group (44.3% vs. 16.9%, P < 0.001). In multivariate analysis, high N slope was identified as a significant independent risk factor for grade II-IV aGVHD, irrespective of the involved organs. There were no differences in relapse, nonrelapse mortality, or overall survival between the two groups. In conclusion, the difference in N slope after allo-HCT may predict the risk of aGVHD. Prevention and treatment of GVHD according to the changes in the neutrophil count may improve post-transplant complications.

Comparison of Danaparoid Sodium and Synthetic Protease Inhibitors for the Treatment of Disseminated Intravascular Coagulation Associated with Hematological Malignancies: A Retrospective Analysis.

BACKGROUND: Danaparoid sodium and synthetic protease inhibitors (SPIs) have been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan. OBJECTIVES: To compare the clinical results of the treatment of DIC with danaparoid or SPIs. METHODS: We retrospectively examined 188 patients with hematological malignancy-related DIC. RESULTS: DIC resolution rate in the danaparoid group was higher than that in the SPIs group (61.5 vs. 42.6%; p = 0.031) on day 7. Multivariate analysis identified the response to chemotherapy as independent predictive factor for DIC resolution on day 7 (odds ratio, OR, 2.28; 95% confidence interval, CI, 1.21-4.31; p = 0.011). While there was no significant difference in the DIC resolution rate on day 14 (75.0 vs. 62.4%; p = 0.117), in a subgroup analysis of patients who did not show an improvement in the underlying disease, the danaparoid group showed a significantly better DIC resolution rate (OR 3.89; 95% CI 1.15-13.2; p = 0.030). There was no difference in the rate of cumulative mortality from bleeding within 28 days between the 2 groups (6.6 vs. 3.3%; p = 0.278). CONCLUSIONS: Danaparoid may be associated with more frequent resolution of DIC in patients with refractory underlying disease.

Updated Clinical Outcomes of Hematopoietic Stem Cell Transplantation Using Myeloablative Total Body Irradiation with Ovarian Shielding to Preserve Fertility.

Myeloablative conditioning regimens are associated with severe gonadal toxicity. To preserve ovarian function, we have been investigating ovarian shielding during total body irradiation (TBI) with a myeloablative dose. In this report, we update the clinical outcomes. Female patients with standard-risk hematologic diseases, aged 40 years or younger, who desired to have children, were included (n = 19). The conditioning regimen consisted of TBI at 12 Gy with ovarian shielding and cyclophosphamide (120 mg/kg) or cytarabine (24 g/m2). Ovarian shielding reduced the actual irradiation dose applied to the ovaries from 12 Gy to 2 to 3 Gy. The median age at hematopoietic stem cell transplantation (HSCT) was 24 years (range, 19 to 33 years). With a median follow-up period of 1449 days (range, 64 to 3694) after HSCT, 5-year overall survival and 1- and 5-year relapse rates were 67%, 17%, and 31%, respectively. Only 2 of 14 patients with acute myeloid or lymphoid leukemia in remission have relapsed thus far. The 6-month and 1-year cumulative rates of menstrual recovery were 42% and 78%, respectively. In all patients with menstrual recovery, menstruation recovered within 1 year. The serum anti-Müllerian hormone (AMH) level tended to gradually increase after menstrual recovery. Three patients with extensive chronic graft-versus-host disease experienced delayed recovery of menstruation and serum AMH. Five pregnancies in 3 patients resulted in normal delivery in 1, selective cesarean operation in 1, current pregnancy in 1, and natural abortion in 2. These results suggest that a myeloablative TBI regimen with ovarian shielding could preserve fertility after HSCT without an apparent increase in relapse in standard-risk patients. Because serum AMH recovered gradually over time, the AMH level during the early phase after HSCT may have little value as a marker of ovarian reserve.

Antitumor activity of potent pyruvate dehydrogenase kinase 4 inhibitors from plants in pancreatic cancer.

Phosphorylation of pyruvate dehydrogenase by pyruvate dehydrogenase kinase 4 (PDK4) 4 inhibits its ability to induce a glycolytic shift. PDK4 expression is frequently upregulated in various cancer tissues, with its elevation being critical for the induction of the Warburg effect. PDK4 is an attractive target for cancer therapy given its effect on shifting glucose metabolism. Previous research has highlighted the necessity of identifying a potent compound to suppress PDK4 activity at the submicromolar concentrations. Here we identified natural diterpene quinones (KIS compounds) that inhibit PDK4 at low micromolar concentrations. KIS37 (cryptotanshinone) inhibited anchorage-independent growth in three-dimensional spheroid and soft agar colony formation assays of KRAS-activated human pancreatic (MIAPaCa-2 and Panc-1) and colorectal (DLD-1 and HCT116) cancer cell lines. KIS37 also suppressed KRAS protein expression in such cell lines. Furthermore, KIS37 suppressed phosphorylation of Rb protein and cyclin D1 protein expression via the PI3K-Akt-mTOR signaling pathway under nonadherent culture conditions and suppressed the expression of cancer stem cell markers CD44, EpCAM, and ALDH1A1 in MIAPaCa-2 cells. KIS37 also suppressed pancreatic cancer cell growth in both subcutaneous xenograft and orthotopic pancreatic tumor models in nude mice at 40 mg/kg (intraperitoneal dose) without any evident toxicity. Reduced ALDH1A1 expression was observed in KIS37-treated pancreatic tumors, suggesting that cancer cell stemness was also suppressed in the orthotopic tumor model. The aforementioned results indicate that KIS37 administration is a novel therapeutic strategy for targeting PDK4 in KRAS-activated intractable human pancreatic cancer.

Predictive value of soluble interlukin-2 receptor level at diagnosis on the outcome for patients with classical Hodgkin lymphoma treated with ABVD with or without radiotherapy.

We retrospectively analyzed 70 patients with classical Hodgkin lymphoma (cHL) who were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiotherapy to assess the influence of the soluble interleukin-2 receptor (sIL-2R) level at diagnosis on the clinical outcome. Receiver operating characteristic analyses determined that the optimal cutoff value of the sIL-2R level for progression-free survival (PFS) was 2490 U/mL. Using this cutoff value, patients were classified into low (n = 46) and high (n = 24) sIL-2R groups. The patients in the high sIL-2R group exhibited a significantly inferior PFS (44.1% vs. 90.4% at 5 years, P < 0.001) and overall survival (OS) (67.6% vs. 94.7% at 5 years, P = 0.001) compared with those in the low sIL-2R group. Multivariate analysis showed that a high sIL-2R level was an independent prognostic factor for PFS after adjusting for stage, white blood cell, hemoglobin, and B symptoms, and also OS after adjusting for age and stage (hazard ratio (HR) 6.49, P < 0.001 and HR 5.98, P = 0.009, respectively). In patients with advanced-stage cHL, a high sIL-2R level predicted 5-year PFS even after adjustment for international prognostic score > 4 (HR 6.00, P = 0.007). These results demonstrate that the sIL-2R level can be a useful prognostic factor in patients with cHL treated with ABVD with or without radiotherapy.

Comparison of blast percentage calculated based on bone marrow all nucleated cells and non-erythroid cells in myelodysplastic syndromes with erythroid hyperplasia.

It is controversial whether blast percentage based on all nucleated cells (ANC) or non-erythroid cells (NEC) more accurately reflects the prognosis of patients with myelodysplastic syndromes (MDS). We considered that the impact of blast percentage on survival should be similar in MDS with erythroid hyperplasia (MDS-E) and MDS with no erythroid hyperplasia (MDS-NE), and from this perspective, we retrospectively analyzed 322 patients, including 44 with MDS-E and 278 with MDS-NE. Overall survival was similar between the MDS-E and MDS-NE groups (P = 0.94). In a subgroup of patients with bone marrow (BM) blasts of < 5%, no difference in survival was found between MDS-E and MDS-NE by either calculation method. However, in patients with a blast percentage between 5 and 10%, a significant difference in survival was observed only when the blast percentage in MDS-E was calculated from ANC (P < 0.001 by ANC and P = 0.66 by NEC). A similar result was observed when we analyzed the remaining patients with higher blasts together with those with blasts between 5 and 10%. These results suggest that the calculation of the BM blast percentage based on NEC in MDS-E provides a blast percentage value with a clinical impact consistent with that in MDS-NE.

TAFRO Syndrome with an Anterior Mediastinal Mass and Lethal Autoantibody-Mediated Thrombocytopenia: An Autopsy Case Report.

TAFRO syndrome, a rare systemic inflammatory disease, can lead to multiorgan failure without appropriate treatment. Although thrombocytopenia is frequently seen in patients with TAFRO syndrome, little is known about its pathogenesis. Moreover, while recent studies have reported the presence of an anterior mediastinal mass in some patients, the pathological status of this remains unclear. Here, we report a case of fatal bleeding in a patient with TAFRO syndrome accompanied by an anterior mediastinal mass. A 55-year-old female was transferred to our hospital with a 2-week history of fever, epistaxis, and dyspnea. Laboratory tests revealed severe thrombocytopenia, computed tomography (CT) showed pleural effusions, and bone marrow biopsy revealed reticulin myelofibrosis. We suspected TAFRO syndrome, but the CT scan showed an anterior mediastinal mass that required a biopsy to exclude malignancy. She soon developed severe hemorrhagic diathesis and died of intracranial hemorrhage despite intensive treatment. She had multiple autoantibodies against platelets, which caused platelet destruction. An autopsy of the mediastinal mass revealed fibrous thymus tissues with infiltration by plasma cells. Our case suggests that thrombocytopenia could be attributed to antibody-mediated destruction and could be lethal. Hence, immediate treatment is imperative in cases of severe thrombocytopenia, even when accompanied by an anterior mediastinal mass.

Comprehensive Analysis of the Activation and Proliferation Kinetics and Effector Functions of Human Lymphocytes, and Antigen Presentation Capacity of Antigen-Presenting Cells in Xenogeneic Graft-Versus-Host Disease.

Xenogeneic graft-versus-host disease (GVHD) models in highly immunodeficient mice are currently being used worldwide to investigate human immune responses against foreign antigens in vivo. However, the individual roles of CD4+ and CD8+ T cells, and donor/host hematopoietic and nonhematopoietic antigen-presenting cells (APCs) in the induction and development of GVHD have not been fully investigated. In the present study, we comprehensively investigated the immune responses of human T cells and the antigen presentation capacity of donor/host hematopoietic and nonhematopoietic APCs in xenogeneic GVHD models using nonobese diabetic/Shi-scid-IL2rgnull mice. CD4+ T cells and, to a lesser extent, CD8+ T cells individually mediated potentially lethal GVHD. In addition to inflammatory cytokine production, CD4+ T cells also supported the activation and proliferation of CD8+ T cells. Using bone marrow chimeras, we demonstrated that host hematopoietic, but not nonhematopoietic, APCs play a critical role in the development of CD4+ T cell-mediated GVHD. During early GVHD, we detected 2 distinct populations in memory CD4+ T cells. One population was highly activated and proliferated in major histocompatibility complex antigen (MHC)+/+ mice but not in MHC-/- mice, indicating alloreactive T cells. The other population showed a less activated and slowly proliferative status regardless of host MHC expression, and was associated with higher susceptibility to apoptosis, indicating nonalloreactive T cells in homeostasis-driven proliferation. These observations are clinically relevant to donor T cell response after allogeneic hematopoietic stem cell transplantation. Our findings provide a better understanding of the immunobiology of humanized mice and support the development of novel options for the prevention and treatment for GVHD.

Chemical synthesis of 4-azido-ß-galactosamine derivatives for inhibitors of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase.

Chondroitin sulfate E (CS-E) plays a crucial role in diverse processes ranging from viral infection to neuroregeneration. Its regiospecific sulfation pattern, generated by N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST), is the main structural determinant of its biological activity. Inhibitors of GalNAc4S-6ST can serve as powerful tools for understanding physiological functions of CS-E and its potential therapeutic leads for human diseases. A family of new 4-acylamino-ß-GalNAc derivatives and 4-azido-ß-GalNAc derivatives were synthesized for their potential application as inhibitors of GalNAc4S-6ST. The target compounds were evaluated for their inhibitory activities against GalNAc4S-6ST. The results revealed that 4-pivaloylamino- and 4-azido-ß-GalNAc derivatives displayed evident activities against GalNAc4S-6ST with IC50 value ranging from 0.800 to 0.828 mM. They showed higher activities than benzyl D-GalNAc4S that was used as control.

Identification and Characterization of a Novel NADPH Oxidase 1 (Nox1) Inhibitor That Suppresses Proliferation of Colon and Stomach Cancer Cells.

Reactive oxygen species (ROS) generated by reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox)1 mediate cellular signalings involved in normal physiological processes, and aberrant control of Nox1 has been implicated in the pathogenesis of various diseases. Therefore, Nox1 could have great potential as a therapeutic target. Here, we identified a novel Nox1 inhibitor, NOS31 secreted from Stretomyces sp. and analyzed its chemical structure. Furthermore, NOS31 was found to selectively inhibit Nox1-mediated ROS generation, with only a marginal effect on other Nox isoforms (Nox2-5) and no ROS scavenging activity. This compound blocked both Nox organizer 1 (NOXO1)/Nox activator 1 (NOXA1)-dependent and phorbol 12-myristate 13-acetate-stimulated Nox1-mediated ROS production in colon cancer cells. NOS31 inhibited the proliferation of several colon carcinoma and gastric cancer cell lines that upregulate the Nox1 system, whereas it had no appreciable effect on normal cells with low levels of Nox1. The finding suggests that NOS31 is a unique, potent Nox1 inhibitor of microbial origin and raises its possibility as a therapeutic agent for inhibiting gastrointestinal cancer cell growth.

False-positive elevation of 1,3-beta-D-glucan caused by continuous administration of penicillin G.

The 1,3-beta-D-Glucan (BDG) assay is widely used for the diagnosis of fungal infections, especially in patients with hematologic malignancies. Some antimicrobials have been reported to cause false-positive results for BDG, but there has been no report on the effect of penicillin G (PCG) on BDG levels. We experienced a patient who developed false-positive BDG elevation during the administration of PCG for osteomyelitis due to Streptococcus pneumoniae infection. The serum BDG level increased up to 81.0 pg/ml during the continuous administration of PCG at 24 million units per day. However, chest and paranasal CT scan showed no evidence of fungal infection. The BDG level decreased to 38.0 pg/ml at 14 hours after the discontinuation of PCG. The amount of BDG in one vial of PCG inferred from these serum BDG levels is very similar to the actual BDG concentration in a vial of PCG. Therefore, during the administration of PCG, elevated BDG levels should be interpreted with caution, as they may be false-positive results.