Inhibition of melanoma cell proliferation by strobilurins isolated from mushrooms and their synthetic analogues.

Strobilurins A and X, isolated from Mucidula venosolamellata culture extracts, demonstrated potent inhibition of human melanoma G-361 cell proliferation. Strobilurin X exhibited milder inhibitory effects on human fibroblast cells (NB1RGB) compared to strobilurin A. Additional strobilurin-related compounds were isolated from the other mushroom species. Oudemansins A and B displayed weaker activities on G-361 cells than strobilurins A and B, respectively, emphasizing the importance of a conjugated double-bond structure. Among isolated compounds, strobilurin G showed the lowest IC50 value for G-361 cells. Additional strobilurins bearing various substituents on the benzene ring were synthesized. Synthetic intermediates lacking the methyl ß-methoxyacrylate group and a strobilurin analogue bearing modified ß-methoxyacrylate moiety showed almost no inhibitory activity against G-361 cells. The introduction of long or bulky substituents at the 4' position of the benzene ring of strobilurins enhanced the activity and selectivity, suggesting differential recognition of the benzene ring by G-361 and NB1RGB cells.

A Case of Jejunal Artery Aneurysm Successfully Treated with Endovascular Embolization.

Jejunal artery aneurysms are extremely rare; only 58 cases have been reported up to 2022. The high rupture rate necessitates a curative treatment. Only four cases of true jejunal artery aneurysms treated with endovascular embolization were reported. We report a case of a 75-year-old man with a true jejunal artery aneurysm who was successfully treated with endovascular embolization. The aneurysm was located in the third jejunal branch. The proximal and distal distance to the superior mesenteric artery and the first bifurcation of the third jejunal branch, respectively, were too short to perform isolation. First, we performed packing in the aneurysm, followed by secondary parent artery embolization. Finally, we achieved total occlusion of the aneurysm and its parent artery with preserved distal intestinal blood flow.

Identification of Cyclocybe erebia metabolites that affect the circadian rhythm of Eluc expression under control of Bmal1 promoter in mouse fibroblast cells.

Pharmacological intervention of circadian rhythms is a potentially useful approach for ameliorating various health problems caused by disturbed circadian rhythms including sleep disorder and metabolic diseases. To find compounds that affect circadian rhythms, we screened mushroom extracts using mouse cells expressing the luciferase gene under the control of the mouse Bmal1 promoter. The culture filtrate extract from the basidiomycete Cyclocybe erebia enhanced the oscillation of bioluminescence caused by the expression of the luciferase gene and prolonged the period of bioluminescence. Bioassay-guided fractionation of the extract resulted in purification of compounds 1 and 2. Spectroscopic analyses along with single-crystal X-ray diffraction analysis, revealed that these compounds were diterpenoids with a unique skeleton and a fused ring system comprising 3-, 7-, and 5-membered rings. Compounds 1 and 2 were named cyclocircadins A and B, respectively. These findings suggested that natural diterpenoids could be a source of compounds with the activity affecting circadian rhythms.

A Case of Refractory Esophageal Varices Caused by an Inferior Mesenteric Arteriovenous Malformation with All Portal System Occlusion Successfully Treated via Transarterial Embolization.

Inferior mesenteric arteriovenous fistulas/malformations are rare, reported in only 40 cases as of 2021. Their main manifestations include portal hypertension and ischemic bowel disease. We report the case of a 50-year-old man with refractory esophageal varices caused by this condition that was successfully treated with transarterial embolization. Computed tomography revealed an inferior mesenteric arteriovenous malformation and ascending blood flow into the esophageal varices through a remarkably dilated marginal vein. All portal systems were occluded, possibly because of the myointimal hyperplasia of the inferior mesenteric vein. The patient recovered without hemorrhagic events after transarterial embolization and endoscopic injection sclerotherapy. This is the first report of an inferior mesenteric arteriovenous malformation resulting in refractory esophageal varices with all-portal system occlusion successfully treated with transarterial embolization.

The diagnostic challenge of non-traumatic bladder rupture: a pictorial essay.

Non-traumatic bladder rupture (NTBR) is relative rare pathology including spontaneous rupture and iatrogenic injury. As increasing the medical intervention for the pelvic malignancy or elderly population, NTBR will be encountered more frequently. There are few previous studies summarizing the imaging features of NTBR. We reviewed imaging characteristics of 18 previous cases of NTBR experienced. In addition, 3 presentative cases that can be a pitfall to differentiate from NTBR. The aim of this article is to clarify the key CT findings of NTBR and its pitfalls.

National survey on total-body irradiation prior to reduced-intensity stem cell transplantation in Japan: The Japanese Radiation Oncology Study Group.

Reduced-intensity stem cell transplantation (RIST) minimizes the adverse effects of traditional hematopoietic stem cell transplantation, and low-dose total-body irradiation (TBI) is administered over a short period prior to RIST (TBI-RIST). Different institutes adopt different approaches for the administration of TBI-RIST, and since no study had previously investigated this issue, a survey of the TBI schedules in Japan was conducted. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of TBI-RIST procedures conducted between 2010 and 2014. Of 186 institutions performing TBI, 90 (48%) responded to the survey, 78 of which performed TBI-RIST. Of 2488 patients who underwent TBI for malignant disease at these institutions, 1412 (56.8%) patients were treated for leukemia, 477 (19.2%) for malignant lymphoma, 453 (18.2) for myelodysplastic syndrome, 44 (1.8%) for multiple myeloma, and 102 (4.1%) for other malignant diseases. Further, 206 (52.0%) of 396 patients (a high proportion of patients) who underwent TBI for benign disease had aplastic anemia. The TBI-RIST equipment and treatment methods were similar to those used for myeloablative regimens. Routinely shielded organs included the lungs (43.6%), eyes (50.0%) and kidneys (10.2%). The ovaries (14.1%), thyroid (6.4%) and testicles (16.7%) were also frequently shielded, possibly reflecting an emphasis on shielding reproductive organs in children. TBI-RIST was performed more frequently than myeloablative conditioning in patients with benign disease. Genital and thyroid shielding were applied more frequently in patients treated with TBI-RIST than in patients treated with myeloablative conditioning. In conclusion, this study indicates the status of TBI-RIST in Japan and can assist future efforts to standardize TBI-RIST treatment methods and to design a future multicenter collaborative research study.

National survey of myeloablative total body irradiation prior to hematopoietic stem cell transplantation in Japan: survey of the Japanese Radiation Oncology Study Group (JROSG).

A myeloablative regimen that includes total-body irradiation (TBI) before hematopoietic stem cell transplantation results in higher patient survival rates than achieved with regimens without TBI. The TBI protocol, however, varies between institutions. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of myeloablative TBI (covering 2010-2014). Among the 186 Japanese institutions performing TBI, 90 (48%) responded. The 82 institutions that had performed myeloablative TBI during this period treated 2698 patients with malignant disease [leukemia (2082 patients, 77.2%), malignant lymphoma (378, 14%)] and 37 with non-malignant disease [severe aplastic anemia (20, 54%), inborn errors of metabolism (5, 14%)]. A linear accelerator was used at all institutions. The institutions were divided into 41 large and 41 small institutions based on the median number of patients. The long source-surface distance technique was the method of choice in the 34 institutions (82.9%) and the moving-couch technique in the 7 (17.1%) in the large institutions. The schedules most routinely used by the participating institutions consisted of 12 Gy/6 fractions/3 days (26 institutions, 63.5%) in the large institutions. The dose rate varied from 5 to 26 cGy/min. The lungs and lenses were routinely shielded in 23 large institutions (56.1%), and only the lungs in 9 large institutions (21.9%). At lung-shielding institutions, the most frequent maximum acceptable total dose for the lungs was 8 Gy (19 institutions, 27.5%). Our results reveal considerable differences in the TBI methods used by Japanese institutions and thus the challenges in designing multicenter randomized trials based on TBI.

Early disease progression in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy.

Prognosis of patients with localized nasal extranodal natural killer/T-cell lymphoma, nasal type (ENKL) has been improved by non-anthracycline-containing treatments such as concurrent chemoradiotherapy (CCRT). However, some patients experience early disease progression. To clarify the clinical features and outcomes of these patients, data from 165 patients with localized nasal ENKL who were diagnosed between 2000 and 2013 at 31 institutes in Japan and who received radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) were retrospectively analyzed. Progression of disease within 2 years after diagnosis (POD24) was used as the definition of early progression. An independent dataset of 60 patients with localized nasal ENKL who received CCRT at Samsung Medical Center was used in the validation analysis. POD24 was documented in 23% of patients who received RT-DeVIC and in 25% of patients in the validation cohort. Overall survival (OS) from risk-defining events of the POD24 group was inferior to that of the reference group in both cohorts (P < .00001). In the RT-DeVIC cohort, pretreatment elevated levels of serum soluble interleukin-2 receptor (sIL-2R), lactate dehydrogenase, C-reactive protein, and detectable Epstein-Barr virus DNA in peripheral blood were associated with POD24. In the validation cohort, no pretreatment clinical factor associated with POD24 was identified. Our study indicates that POD24 is a strong indicator of survival in localized ENKL, despite the different CCRT regimens adopted. In the treatment of localized nasal ENKL, POD24 is useful for identifying patients who have unmet medical needs.

Walking Disability in Patients with Pelvic Insufficiency Fracture after Radiotherapy for Uterine Cervical Cancer.

OBJECTIVE: Radiotherapy is an essential component of curative or palliative therapy for patients with uterine cervical cancer. Although advances in radiotherapy have led to longer survival, survivors may consequently be at risk of pelvic insufficiency fracture (PIF). We retrospectively reviewed medical records and clinical outcomes to assess the impact of PIF on walking disability. METHODS: Between January 2002 and December 2009, 145 uterine cancer patients treated with radiotherapy in our hospital were reviewed. Among these, 15 patients (10.3%) were diagnosed with PIF. The types of fractures were identified according to the AO/OTA classification system. Medical records were examined to establish the time to first diagnosis of PIF, the type of fracture, and clinical outcomes. Disability was assessed using Barthel index mobility scores. RESULTS: The median time to PIF detection was 16 months. Of the 15 patients with PIF, 14 had type B fractures (7 cases of B2 and 7 cases of B3) and 1 had a type C fracture. Among 11 patients with pelvic pain, 6 achieved pain control but 5 patients with bilateral lesions in the posterior arch or lateral compression of the sacrum developed pain that finally resulted in walking disability and a lower performance status. CONCLUSIONS: PIF causes severe motor disturbance in patients with unstable fracture types. Routine imaging checkups were useful during the 5 years after completion of radiotherapy; in nine patients the fracture progressed for longer than 1 year. In cancer rehabilitation for PIF patients, continuous assessment is essential for predicting walking disability.