Nuclear receptor family proteins are structurally related transcription factors activated by specific lipophilic compounds. Because they are activated by a variety of hormonal molecules, including retinoic acid, vitamin D, and steroid hormones, they are assumed to be promising targets for clinical drugs. We previously found that one ascochlorin (1) derivative, 4-O-carboxymethyl-ascochlorin (2), is a potent agonist of peroxisome proliferator activated receptor gamma (PPARgamma). Here, we synthesized derivatives of 1, designated as a lead compound, to create new modulators of nuclear hormone receptors. Two derivatives, 4-O-carboxymethyl-2-O-methylascochlorin (9) and 4-O-isonicotinoyl-2-O-methylascochlorin (10), showed improved agonistic activity for PPARgamma and induced differentiation of a progenitor cell line, C3H10T1/2. We also found that 1, dehydroascofuranon (29), and a 2,4-O-diacetyl-1-carboxylic acid derivative of 1 (5) specifically activated estrogen receptors, PPARalpha, and an androgen receptor. All of the derivatives (1-29) activated the pregnane X receptor. These results suggest that the chemical structure of 1 is useful in designing novel modulators of nuclear receptors.

Endoscopic submucosal dissection (ESD) for colorectal neoplasms remains challenging because of technical issues imposed by the complex anatomical features of the large intestine. We evaluated the feasibility, and the short- and long-term clinical outcomes of ESD for early colorectal neoplasms performed using the Stag-beetle Knife Jr. (SB Knife Jr.) We retrospectively assessed 228 patients who underwent ESD for 247 colorectal lesions with the SB Knife Jr. Clinicopathological characteristics of the neoplasms, complications, and various short- and long-term outcomes were evaluated. Mean tumor size was 34.3 mm and median procedure time was 76 minutes. The SB Knife Jr. achieved 98.4 % en bloc resection, 93.9 % complete resection, and 85.4 % curative resection. No perforations occurred during the procedure, and a delayed bleeding rate of 2.4 % was observed. Long-term outcomes were favorable with no distant recurrence, 1.1 % local recurrence, a 5-year overall survival rate of 94.1 % and 5-year tumor-specific survival rate of 98.6 % in patients with cancer. ESD using the SB Knife Jr. is technically efficient and safe in treating early colorectal neoplasms and is associated with favorable short- and long-term outcomes.

AIMTo determine short- and long-term outcomes of endoscopic submucosal dissection (ESD) using the stag beetle (SB) knife, a scissor-shaped device.METHODSSeventy consecutive patients with 96 early esophageal neoplasms, who underwent ESD using a SB knife at Kure Medical Center and Chugoku Cancer Center, Japan, between April 2010 and August 2016, were retrospectively evaluated. Clinicopathological characteristics of lesions and procedural adverse events were assessed. Therapeutic success was evaluated on the basis of en bloc, histologically complete, and curative or non-curative resection rates. Overall and tumor-specific survival, local or distant recurrence, and 3- and 5-year cumulative overall metachronous cancer rates were also assessed.RESULTSEligible patients had dysplasia/intraepithelial neoplasia (22%) or early cancers (squamous cell carcinoma, 78%). The median procedural time was 60 min and on average, the lesions measured 24 mm in diameter, yielding 33-mm tissue defects. The en bloc resection rate was 100%, with 95% and 81% of dissections deemed histologically complete and curative, respectively. All procedures were completed without accidental incisions/perforations or delayed bleeding. During follow-up (mean, 35 ± 23 mo), no local recurrences or metastases were observed. The 3- and 5-year survival rates were 83% and 70%, respectively, with corresponding rates of 85% and 75% for curative resections and 74% and 49% for non-curative resections. The 3- and 5-year cumulative rates of metachronous cancer in the patients with curative resections were 14% and 26%, respectively.CONCLUSIONESD procedures using the SB knife are feasible, safe, and effective for treating early esophageal neoplasms, yielding favorable short- and long-term outcomes.

The phase shifts of a simple gradient echo (fast low-angle shot) were correlated with the local change in resonance frequency due to the differences in susceptibility among tissues (susceptibility effect). Susceptibility effects were considered theoretically, and the phase shifts for spherical and cylindrical configurations were calculated. A 1.5-T magnetic resonance unit and phantoms filled with solutions of copper chloride in water were used to obtain the phase images. The phase shifts of the simple gradient echo coincided with the values calculated with use of the sum of the macroscopic magnetic field and the cavity field of Lorentz. The authors conclude that the gap of the phase shifts at interfaces of tissues is useful in the evaluation of differences in magnetic susceptibility among tissues.

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Objectives There are some endoscopic resection (ER) methods for neuroendocrine tumors (NETs), however, which method is most useful remains unclear. This study aimed to compare the outcomes of different ER techniques, such as conventional endoscopic mucosal resection (cEMR), endoscopic submucosal dissection (ESD), and endoscopic submucosal resection with a ligation device (ESMR‐L) for rectal NETs. Methods We retrospectively analyzed 96 consecutive patients with 102 rectal NETs of less than 10 mm in diameter who underwent ER between January 2001 and December 2019 at Hiroshima University Hospital. We compared the clinical outcomes of each ER method (cEMR 60 lesions, ESD 21 lesions, and ESMR‐L 21 lesions), divided according to the treatment periods, and evaluated the risk factors for vertical margin (VM) positivity in relation to clinicopathological and endoscopic characteristics. Results As for the mean procedure time, ESD took significantly longer to perform than the other methods. The histological complete resection rate was 80% (48/60) for cEMR, 85.7% (18/21) for ESD, and 100% (21/21) for ESMR‐L, and the VM positive rate was 20% (12/60) for cEMR, 14.3% (3/21) for ESD, and 0% (0/21) for ESMR‐L, with no significant difference. However, the tumor‐front‐to‐VM distance was significantly longer in the ESMR‐L group than in the cEMR and ESD groups. cEMR and ESD were both significant risk factors for VM positivity. No perforation or local recurrence was observed in all methods. Conclusions ESMR‐L is the most useful ER method for small rectal NETs.

Objectives A single‐balloon overtube (SBO) can improve poor scope operability during colonic endoscopic submucosal dissection (ESD). We aimed to evaluate the clinical usefulness of SBO for ESD in the proximal colon and the predictive factors for cases in which SBO is useful. Methods A total of 88 tumors located in the proximal colon resected by balloon‐assisted ESD (BA‐ESD) using SBO and 461 tumors resected by conventional ESD (C‐ESD) between June 2015 and November 2020 were considered. Seventy‐eight tumors each in the BA‐ESD and C‐ESD groups were matched by propensity score matching. ESD outcomes were compared between the groups, and a decision tree analysis was performed to explore the predictive factors for cases in which SBO is useful. Results There were no significant differences between the groups in the major outcomes such as en bloc resection rate (95% vs. 99%, p = 0.17), R0 resection rate (92% vs. 96%, p = 0.30), mean dissection speed (16 mm 2 /min vs. 16 mm 2 /min, p = 0.53), and intraoperative perforation rate (5% vs. 6%, p = 0.73). Even when considering cases with poor preoperative scope operability, there were no significant differences between the groups. Comparison of tumors ≥40 mm in diameter between the groups confirmed that the intraoperative perforation rate was significantly lower in the BA‐ESD group than in the C‐ESD group (0% vs. 24%, p = 0.0188). Conclusion SBO is useful for ESD of tumors ≥40 mm in diameter in the proximal colon to prevent intraoperative perforation, which usually has a long procedure time.