Chamaecyparis obtusa

Chamaecyparis obtusa (C. obtusa) is known to have antimicrobial effects and has been used as a medicinal plant and in forest bathing. This study aimed to evaluate the anticariogenic activity of essential oil of C. obtusa on Streptococcus mutans, which is one of the most important bacterial causes of dental caries and dental biofilm formation. Essential oil from C. obtusa was extracted, and its effect on bacterial growth, acid production, and biofilm formation was evaluated. C. obtusa essential oil exhibited concentration-dependent inhibition of bacterial growth over 0.025 mg/mL, with 99% inhibition at a concentration of 0.2 mg/mL. The bacterial biofilm formation and acid production were also significantly inhibited at the concentration greater than 0.025 mg/mL. The result of LIVE/DEAD® BacLight™ Bacterial Viability Kit showed a concentration-dependent bactericidal effect on S. mutans and almost all bacteria were dead over 0.8 mg/mL. Real-time PCR analysis showed that gene expression of some virulence factors such as brpA, gbpB, gtfC, and gtfD was also inhibited. In GC and GC-MS analysis, the major components were found to be α-terpinene (40.60%), bornyl acetate (12.45%), α-pinene (11.38%), β-pinene (7.22%), β-phellandrene (3.45%), and α-terpinolene (3.40%). These results show that C. obtusa essential oil has anticariogenic effect on S. mutans

Differential T-cell and monocyte responses in hepatocellular carcinoma treated with regorafenib plus nivolumab: an integrated clinical and biomarker analysis of the phase 2 RENOBATE trial

<p>Regorafenib plus nivolumab (RegoNivo) combination has shown promising anti-cancer activity in multiple cancer types. REBNOBATE trial is a single-arm multicenter phase 2 trial of first-line RegoNivo in patients (pts) with uHCC (NCT04310709). Here we report the clinical outcomes of the RENOBATE study and integrative biomarker analysis using circulating tumor DNA (ctDNA) and single cell RNA sequencing (scRNA-seq) analysis.</p&gt

Differential T-cell and monocyte responses in hepatocellular carcinoma treated with regorafenib plus nivolumab: an integrated clinical and biomarker analysis of the phase 2 RENOBATE trial

Regorafenib plus nivolumab (RegoNivo) combination has shown promising anti-cancer activity in multiple cancer types. REBNOBATE trial is a single-arm multicenter phase 2 trial of first-line RegoNivo in patients (pts) with uHCC (NCT04310709). Here we report the clinical outcomes of the RENOBATE study and integrative biomarker analysis using circulating tumor DNA (ctDNA) and single cell RNA sequencing (scRNA-seq) analysis

Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial

<p><span>Regorafenib has anti-tumor activity in hepatocellular carcinoma (HCC) with potential immunomodulatory effects, suggesting its combination with immune checkpoint inhibitor may have clinically meaningful benefits in unresectable HCC patients. <a><span>The</span></a></span><span><span><span></span></span></span><span><span><span> </span></span></span><span> multicenter single-arm phase 2 RENOBATE trial tested regorafenib-nivolumab as front-line treatment for unresectable HCC. Forty-two patients received nivolumab 480 mg/4 weeks, and regorafenib 80 mg/daily (3-weeks on/1-week off schedule). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS). ORR per RECIST v1.1 was 31.0%, meeting the primary endpoint. The most common adverse events were hand-foot skin reaction (33.3%), alopecia (26.2%), and skin rash (21.4%)</span><span><span><span></span></span></span><span>. Median PFS was 7.38 months. The 1-year OS rate was 80.5%, while the median OS was not reached. Exploratory single-cell RNA sequencing analyses of peripheral blood mononuclear cells show thatlong-term responders exhibited T-cell-receptor repertoire diversification; enrichment of genes representing immunotherapy-responsiveness in <em>MKI67</em><sup>+</sup> proliferating CD8<sup>+</sup> T cells; and a higher probability of M1-directed monocyte polarization. Our data support further clinical development of the regorafenib-nivolumab combination as front-line treatment for unresectable HCC and provide preliminary insights on immune biomarkers of response ClinicalTrials.gov identifier: </span><span><a href="https://clinicaltrials.gov/study/NCT04310709?cond=HCC&intr=regorafenib%20nivolumab&rank=1"><span>NCT04310709</span></a></span><span>.</span></p&gt