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1.
Safety and immunogenicity of SARS-CoV-2 self-amplifying RNA vaccine expressing an anchored RBD: A randomized, observer-blind phase 1 study.
Akahata, W, Sekida, T, Nogimori, T, Ode, H, Tamura, T, Kono, K, Kazami, Y, Washizaki, A, Masuta, Y, Suzuki, R, et al
Cell reports. Medicine. 2023;(8):101134
Abstract
VLPCOV-01 is a lipid nanoparticle-encapsulated self-amplifying RNA (saRNA) vaccine that expresses a membrane-anchored receptor-binding domain (RBD) derived from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. A phase 1 study of VLPCOV-01 is conducted (jRCT2051210164). Participants who completed two doses of the BNT162b2 mRNA vaccine previously are randomized to receive one intramuscular vaccination of 0.3, 1.0, or 3.0 μg VLPCOV-01, 30 μg BNT162b2, or placebo. No serious adverse events have been reported. VLPCOV-01 induces robust immunoglobulin G (IgG) titers against the RBD protein that are maintained up to 26 weeks in non-elderly participants, with geometric means ranging from 5,037 (95% confidence interval [CI] 1,272-19,940) at 0.3 μg to 12,873 (95% CI 937-17,686) at 3 μg compared with 3,166 (95% CI 1,619-6,191) with 30 μg BNT162b2. Neutralizing antibody titers against all variants of SARS-CoV-2 tested are induced. VLPCOV-01 is immunogenic following low-dose administration. These findings support the potential for saRNA as a vaccine platform.
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2.
Predictors of early death, serious hemorrhage, and differentiation syndrome in Japanese patients with acute promyelocytic leukemia.
Minamiguchi, H, Fujita, H, Atsuta, Y, Asou, N, Sakura, T, Ueda, Y, Sawa, M, Dobashi, N, Taniguchi, Y, Suzuki, R, et al
Annals of hematology. 2020;(12):2787-2800
Abstract
Significant advancements have been achieved with regard to the outcomes of acute promyelocytic leukemia (APL) patients through the introduction of all-trans retinoic acid; however, early hemorrhagic death and differentiation syndrome remain the major causes of remission induction failure in patients with APL. To investigate early death, serious hemorrhage, and differentiation syndrome during remission induction therapy in terms of incidence, risk factors, influence on outcomes, and prophylactic effects of several new anticoagulants, the results of 344 patients enrolled in the Acute Promyelocytic Leukemia 204 study conducted by the Japan Adult Leukemia Study Group were analyzed. Early death was observed in 16 patients (4.7%), of whom 14 had serious hemorrhage and 2 had differentiation syndrome. Serious hemorrhage and differentiation syndrome of grade 2 or higher were observed in 21 and 54 patients, respectively. Patients who achieved complete remission had a 7-year disease-free survival of 84.8% if they did not experience serious hemorrhage and 40.0% if they experienced serious hemorrhage during remission induction therapy (P = 0.001). Risk factor analyses showed that higher white blood cell count was associated with early death, higher white blood cell count and lower platelet count with serious hemorrhage, and leukocytosis during induction therapy and higher body surface area with differentiation syndrome. In conclusion, these results indicate that patients with such high-risk features may benefit from more intensive supportive care. The hemorrhagic risk was not relieved by the introduction of new anticoagulants. Further studies are required to establish the predictive impact of body surface area on differentiation syndrome. This trial is registered with UMIN-CTR as C000000154 on September 13, 2005.
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3.
A multicenter phase 2 study of empirical low-dose liposomal amphotericin B in patients with refractory febrile neutropenia.
Miyao, K, Sawa, M, Kurata, M, Suzuki, R, Sakemura, R, Sakai, T, Kato, T, Sahashi, S, Tsushita, N, Ozawa, Y, et al
International journal of hematology. 2017;(1):79-86
Abstract
Invasive fungal infection (IFI) is a major life-threatening problem encountered by patients with hematological malignancies receiving intensive chemotherapy. Empirical antifungal agents are therefore important. Despite the availability of antifungal agents for such situations, the optimal agents and administration methods remain unclear. We conducted a prospective phase 2 study of empirical 1 mg/kg/day liposomal amphotericin B (L-AMB) in 80 patients receiving intensive chemotherapy for hematological malignancies. All enrolled patients were high-risk and had recurrent prolonged febrile neutropenia despite having received broad-spectrum antibacterial therapy for at least 72 hours. Fifty-three patients (66.3 %) achieved the primary endpoint of successful treatment, thus exceeding the predefined threshold success rate. No patients developed IFI. The treatment completion rate was 73.8 %, and only two cases ceased treatment because of adverse events. The most frequent events were reversible electrolyte abnormalities. We consider low-dose L-AMB to provide comparable efficacy and improved safety and cost-effectiveness when compared with other empirical antifungal therapies. Additional large-scale randomized studies are needed to determine the clinical usefulness of L-AMB relative to other empirical antifungal therapies.
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4.
Gastric endoscopic submucosal dissection using sodium carboxymethylcellulose as a new injection substance.
Hikichi, T, Yamasaki, M, Watanabe, K, Nakamura, J, Sato, M, Takagi, T, Suzuki, R, Sugimoto, M, Kikuchi, H, Konno, N, et al
Fukushima journal of medical science. 2016;(1):43-50
Abstract
AIM: To investigate the feasibility of endoscopic submucosal dissection (ESD) using sodium carboxymethylcellulose (SCMC) for gastric cancer. METHODS During October 2011 through April 2013, 98 lesions from 98 patients who underwent ESD using SCMC (ESD-SCMC) for early gastric cancer were enrolled in this study. Two endoscopists, who had each performed fewer than 30 ESD procedures (less-experienced ESD physicians), performed ESD-SCMC under the supervision of two experts. The primary outcome was the en bloc resection rate. Secondary outcomes included the complete resection rate, the procedural time, the bleeding rate after SCMC injection, and complications. Patient characteristics, time necessary for hemostasis after SCMC injection, rate of treatment completion by less-experienced ESD physicians alone, and the effects of SCMC during ESD and on resected specimens were also evaluated. RESULTS The en bloc resection rate was 100%. Among these resections, 87.8% of the cases were completed by a less-experienced ESD physician alone. The complete resection rate was 98.0%. The mean total procedural time was 75.4 min. The mean incidence of intraoperative bleeding following SCMC local injection was 1.7 times. No bleeding was observed after SCMC injection in 29.6% of cases (29/98). Five complications occurred: one case of microperforation (1.0%) and four cases of postoperative bleeding (4.0%). SCMC remained in the submucosa. The submucosa was readily manipulated when the deep submucosa was dissected, even after placing the specimen on a slide. CONCLUSION ESD-SCMC is feasible for the resection of early gastric cancer.
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5.
Oral rabeprazole administration on a procedure day suppresses bleeding after endoscopic submucosal dissection for gastric neoplasms.
Hikichi, T, Sato, M, Watanabe, K, Nakamura, J, Takagi, T, Suzuki, R, Sugimoto, M, Waragai, Y, Kikuchi, H, Konno, N, et al
Fukushima journal of medical science. 2014;(1):68-74
Abstract
AIM: The efficacy of pre-procedure oral proton pump inhibitor (PPI) administration for gastric endoscopic submucosal dissection (ESD) is unclear. This study evaluated oral PPI administration effectiveness on the day of ESD to prevent post-ESD bleeding. METHODS This study examined 55 patients who underwent ESD for gastric neoplasm. Group A comprised 31 patients who took rabeprazole sodium (RPZ) 20 mg/day beginning 7-8 hr before ESD. Group B comprised 24 who took RPZ 20 mg/day beginning three days before ESD. Gastric pH (G-pH) was measured at one month before ESD (pre-ESD pH), immediately before ESD (ESD pH), and seven days after ESD (post-ESD pH). The post-ESD bleeding rate and changes in G-pH were recorded. RESULTS No significant difference in post-ESD bleeding rates was found (Group A 3.2%, Group B 0%). ESD pH and post-ESD pH were significantly higher than pre-ESD pH in both groups (P<0.001). The ESD pH for Group A was higher than 6 (6.5±1.1), providing hemostasis for intragastric bleeding. CONCLUSIONS Oral RPZ administration on the day of gastric ESD can suppress post-ESD bleeding equivalently to administration three days before ESD.
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6.
Validity of positron emission tomography using fluoro-2-deoxyglucose for the preoperative evaluation of endometrial cancer.
Suzuki, R, Miyagi, E, Takahashi, N, Sukegawa, A, Suzuki, A, Koike, I, Sugiura, K, Okamoto, N, Inoue, T, Hirahara, F
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2007;(4):890-6
Abstract
To clarify the validity of positron emission tomography using fluoro-2-deoxyglucose (FDG-PET) for the preoperative evaluation of endometrial cancer, we analyzed the preoperative FDG-PET images of both primary and metastatic lesions of 30 patients with endometrial cancer, and compared them with computed tomography (CT) and/or magnetic resonance imaging (MRI) images and the results of postoperative pathologic findings. As to the primary lesions, FDG-PET could easily identify the cancer, and the sensitivity was 96.7%, which tended to be higher than that of 83.3% by CT/MRI. As to the evaluation of retroperitoneal lymph node metastasis, FDG-PET could detect none of five cases of lymph node metastatic lesions of up to 0.6 cm in diameter but had higher specificity (100%) compared with CT/MRI (85.7%). The sensitivity of FDG-PET for detection of extrauterine lesions excluding retroperitoneal lymph nodes was 83.3% and was superior to that of CT/MRI (66.7%), although there was no difference in the specificity between the modalities (100%). The diagnostic ability of FDG-PET was limited if used alone, but FDG-PET gave additional information especially with regard to the extrauterine lesions whose significance could not be determined on CT/MRI. However, we also found that FDG-PET could not identify any lymph node metastasis less than 1 cm in diameter; therefore, a negative finding of lymph node metastasis on FDG-PET should not be interpreted as a reason for omitting retroperitoneal lymph node dissection for the precise surgical staging of endometrial cancer.
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7.
Phase I/II study of escalating doses of nedaplatin in combination with irinotecan for advanced non-small-cell lung cancer.
Oshita, F, Yamada, K, Kato, Y, Ikehara, M, Noda, K, Tanaka, G, Nomura, I, Suzuki, R, Saito, H
Cancer chemotherapy and pharmacology. 2003;(1):73-8
Abstract
We conducted a phase I/II study of combination chemotherapy with nedaplatin (NDP) and irinotecan to determine the effects against advanced non-small-cell lung cancer (NSCLC) and to determine the qualitative and quantitative toxicities of the combination chemotherapy. NDP was given on day 1 and irinotecan on days 1 and 8. The treatment cycle was designed to be repeated every 3 weeks. We fixed the dose of irinotecan as 60 mg/m(2) and escalated the NDP dose from a starting dose of 50 mg/m(2) by 10-mg/m(2) increments until the maximum tolerated dose (MTD) was reached. The MTD was defined as the dose level at which at least two of three or three of six patients experienced a dose-limiting toxicity (DLT). Between April 1997 and November 2000, 42 patients were registered in the study. Of the 42 patients, 37 had no prior treatment, 3 had received whole-brain irradiation, 1 had undergone surgical resection, and 1 had had one regimen of chemotherapy before enrolling in this study. In the phase I study, we observed DLTs such as grade 4 neutropenia lasting 7 days and grade 3 diarrhea lasting 1 day in one patient at level 2, grade 3 elevated of GPT in one patient at level 3, and acute myocardial infarction in one patient at level 6. We could not determine the MTD until dose level 6 was reached, so decided on a recommended dose of 100 mg/m(2) NDP, which is recommended for NDP-alone chemotherapy. Because of prolonged neutropenia in the phase I study, we repeated the treatment every 4 weeks in the phase II study. In the phase II study, a total of 16 patients, including 6 patients from the phase I study, were registered and a total of 42 cycles were administered. Grade 3 or 4 neutropenia, grade 3 anemia and grade 3 or 4 thrombocytopenia occurred in 50%, 12% and 7% of cycles, respectively. Febrile neutropenia occurred in eight cycles (19%) but there were no severe infections. Grade 3 elevation of GPT occurred in one patient. Of the 16 patients, 7 had an objective response. Of the 42 patients, 13 achieved a partial response (PR) and the overall response rate was 31.0%. The median duration of PRs was 226 days (range 59 to 646 days). The median survival time was 341 days and the 1-year survival rate was 45.2%. In conclusion, the combination of NDP and irinotecan was highly effective and well tolerated in NSCLC.