Signal Transducer and Activator of Transcription 3 (STAT3) is a latent cytoplasmic protein overexpressed in various cancer cell lines. STAT3 participates in oncogenesis by stimulating cell proliferation and preventing apoptosis and it has been proven as a suitable target for anticancer therapy. In order to identify direct STAT3 inhibitors, we performed a binding assay on several previously synthesized 1,2,5-oxadiazole derivatives. Among them, compound MD77, N-[4-(4-chlorophenyl)-1,2,5-oxadiazol-3-yl]-4-(trifluoromethyl)benzamide, showed a good ability to bind the STAT3-SH2 domain in a dose-dependent manner (IC 50 ¼ 17.7 mM). Computational studies were carried out to investigate its binding mode. Moreover, compound MD77 showed a significant antiproliferative activity versus several tumor cell lines. On these bases, compound MD77 was selected as a lead for the future development of direct STAT3 inhibitors.

The Ministry of Health, Labour and Welfare approved a drug called Borofalan ( 10 B), a treatment system, and a dose calculation program for boron neutron capture therapy (BNCT) in March 2020.The application pertaining to the products submitted to the Pharmaceuticals and Medical Devices Agency was supported by a Japanese open-label uncontrolled trial (Study 002) in patients with unresectable locally recurrent head and neck squamous cell carcinoma after chemoradiotherapy or radiotherapy, or in those with unresectable locally advanced or locally recurrent (LA/LR) head and neck non-squamous cell carcinoma. The drug was administered as a single intravenous dose using infusion rates of 200 mg/kg/h for the first two hours after the start of administration and 100 mg/kg/h during irradiation. Neutrons irradiation was performed using the devices at a single dose of 12 Gy-Eq. for oral, pharyngeal, or laryngeal mucosa for up to 60 minutes from two hours after the start of drug administration. The primary endpoint was the overall response rate (ORR).The results of Study 002 showed that the ORR [90% confidence interval (CI)] (%) based on an assessment of the Independent Central Review Committee per Response Evaluation Criteria in Solid Tumors (RECIST) ver.1.1 was 71.4 [51.3, 86.8]. The lower limit of the 90% CI exceeded the pre-specified threshold for ORR. When BNCT is applied to patients with unresectable LA/LR head and neck cancer, precautions should be taken, and patients should be monitored for possible onset of dysphagia, brain abscess, skin disorder, crystal urine, cataract, and/or carotid hemorrhage. The Oncologist 2021;9999:• • Implications for Practice: Borofalan ( 10 B), a treatment system, and a dose calculation program for boron neutron capture therapy (BNCT) have demonstrated significant efficacy based on the result of an open-label uncontrolled trial (Study 002) in which the overall response rate was determined as the primary endpoint for patients with unresectable locally advanced or locally recurrent head and neck cancer. Although no information about survival benefits has been obtained, the BNCT will become an effective treatment option that is expected to manage local lesions that are intractable with any standard therapy. In addition, the BNCT is expected to maintain the quality of life of the intended patient population, on account of its high tumor selectivity and low invasiveness.

It is unclear whether the use of antibiotics is related to the efficacy of gemcitabine plus nab-paclitaxel (GnP). Therefore, we investigated the association between the use of antibiotics and efficacy of GnP. We conducted a retrospective single center study from January 2014 to December 2018 in Hokkaido University Hospital. Ninety-nine patients were eligible for the study. Thirty-seven used antibiotics (U) and 62 did not use antibiotics (NU) during GnP therapy. In the U group, 15 patients used β-lactam antibiotics, 21 used new quinolones, and 1 used carbapenem. The median progression-free survival was 5.8 and 2.7 months (hazards ratio [HR] .602, 95% confidence interval [CI] .391–.928, P = .022) and the median overall survival was 11.0 and 8.4 months (HR .768, 95% CI .491–1.202, P = .248) in the U and not use antibiotics groups, respectively. Antibiotic use (HR .489, 95% CI .287–.832, P = .008) and locally advanced pancreatic cancer (HR 1.808, 95% CI 1.051–3.112, P = .032) were independent prognostic factors for progression-free survival. Antibiotic use was associated with a higher efficacy of GnP, and therefore, it may be employed as a novel treatment strategy.

Hepatitis C virus (HCV) infection remains the main cause of liver disease and can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV may also develop extrahepatic manifestations in the skin, eyes, joints, kidneys, nervous system, and immune system. In fact, several studies reported that up to 70% of HCV patients experienced extrahepatic manifestations. Lichen planus (LP), which is an immune system disorder that is triggered by viral infections, allergens, and stress, can affect the skin, mouth, nails, and scalp. The association of LP with HCV has been reported, but the effect of HCV treatment on LP remission is controversial. We encountered a 53-year-old man with HCV genotype 2a and LP that were successfully treated with sofosbuvir and ribavirin for 12 weeks. After treatment, he achieved sustained virological response against HCV and remission of erosive LP lesions on the lip. In the era of interferon (IFN)-based treatment for HCV, exacerbation of autoimmune diseases is a common adverse event. Therefore, use of an IFN-free regimen of direct-acting antivirals for HCV might prevent the extrahepatic manifestation of an immune disorder.

Purpose Dysgeusia is an adverse event caused by chemotherapy. Although retrospective studies have shown zinc administration improves dysgeusia, there have been no prospective studies. The present study examined effects of zinc therapy on dysgeusia in patients with gastrointestinal cancer. Methods This multicenter, prospective, observational study enrolled patients with dysgeusia during chemotherapy treatment. Patients received no intervention (control), polaprezinc p.o., or zinc acetate hydrate p.o., and serum zinc levels were measured at 0 (baseline), 6, and 12 weeks. Dysgeusia was assessed using CTCAE v5.0 and subjective total taste acuity (STTA) criteria using questionnaires at baseline and 12 weeks. Results From February 2020 to June 2021, 180 patients were enrolled from 17 institutes. There were no differences in mean baseline serum zinc levels among the groups (67.3, 66.6, and 67.5 μg/dL in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. P = 0.846). The changes in mean serum zinc levels after 12 weeks were − 3.8, + 14.3, and + 46.6 μg/dL, and the efficacy rates of dysgeusia were 33.3%, 36.8%, and 34.6% using CTCAE and 33.3%, 52.6%, 32.7% using STTA in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. The STTA scores improved in all groups, with significant improvement observed in the polaprezinc group compared with the no intervention group (P = 0.045). Conclusion There was no significant correlation between the degree of serum zinc elevation and improvement in dysgeusia, suggesting that polaprezinc, but not zinc acetate hydrate, was effective in improving chemotherapy-induced dysgeusia. Trial registration. UMIN000039653. Date of registration: March 2, 2020.

No abstract

IRIS does not necessitate the continuous infusion of 5-FU and is more convenient.• The recommended dose of OX-IRIS was determined to be level À 1 (oxaliplatin, 65 mg/m 2 ; irinotecan, 100 mg/m 2 ; S-1, 80 mg/m 2 ), which has manageable safety and promising anticancer activities.

Dyskalemia (hypokalemia and hyperkalemia) is a common comorbidity of heart failure (HF). Although dyskalemia is associated with poor prognosis, different prognostic impacts of hypo- and hyperkalemia remain vastly unclear. This study investigated the association of dyskalemia with prognosis in HF patients, especially the mode of death and left ventricular ejection fraction (LVEF). The multicenter study included 3398 patients hospitalized for HF. Patients were divided into three groups based on serum potassium levels at discharge: hypokalemia (<3.5 mEq/L; n = 115 (3.4%)), normokalemia (3.5–5.0 mEq/L; n = 2960 (87.1%)), and hyperkalemia (≥5.0 mEq/L; n = 323 (9.5%)). Two-year all-cause, cardiac, and non-cardiac mortality was evaluated. Association of serum potassium with two-year mortality demonstrated a U-shaped curve, with a worse prognosis for patients with hypokalemia. All-cause mortality at two-years did not differ among the three groups. Hypokalemia was associated with 2-year cardiac death (adjusted hazard ratio (HR), 2.60; 95% confidence interval (CI), 1.20–5.64) in HF with reduced ejection fraction (HFrEF; LVEF < 40%), but not in non-HFrEF. Regardless of LVEF, hyperkalemia was not independently associated with any mortality. Hypokalemia was independently associated with cardiac death, particularly in HFrEF patients. Such an association was not observed in hyperkalemia regardless of LVEF.