ObjectiveHIF-1/HRE pathway is a promising target for the imaging and the treatment of intractable malignancy (HIF-1; hypoxia-inducible factor 1, HRE; hypoxia-responsive element). The purposes of our study are: (1) to assess the gene activation levels resulting from various numbers of HREs under various hypoxic conditions, (2) to evaluate the bidirectional activity of multiple HREs, and (3) to confirm whether multiple HREs can induce gene expression in vivo.MethodsHuman colon carcinoma HCT116 cells were transiently transfected by the constructs containing a firefly luciferase reporter gene and various numbers (2, 4, 6, 8, 10, and 12) of HREs (nHRE+, nHRE−). The relative luciferase activities were measured under various durations of hypoxia (6, 12, 18, and 24 h), O2 concentrations (1, 2, 4, 8, and 16 %), and various concentrations of deferoxamine mesylate (20, 40, 80, 160, and 320 µg/mL growth medium). The bidirectional gene activation levels by HREs were examined in the constructs (dual-luc-nHREs) containing firefly and Renilla luciferase reporter genes at each side of nHREs. Finally, to test whether the construct containing 12HRE and the NIS reporter gene (12HRE-NIS) can induce gene expression in vivo, SPECT imaging was performed in a mouse xenograft model.Results(1) gene activation levels by HREs tended to increase with increasing HRE copy number, but a saturation effect was observed in constructs with more than 6 or 8 copies of an HRE, (2) gene activation levels by HREs increased remarkably during 6–12 h of hypoxia, but not beyond 12 h, (3) gene activation levels by HREs decreased with increasing O2 concentrations, but could be detected even under mild hypoxia at 16 % O2, (4) the bidirectionally proportional activity of the HRE was confirmed regardless of the hypoxic severity, and (5) NIS expression driven by 12 tandem copies of an HRE in response to hypoxia could be visualized on in vivo SPECT imaging.ConclusionThe results of this study will help in the understanding and assessment of the activity of multiple HREs under hypoxia and become the basis for hypoxia-targeted imaging and therapy in the future.

The inhibitory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and linoleic acid (LA) on the contractions induced by five prostanoids and U46619 (a TP receptor agonist) were examined in guinea pig gastric fundus smooth muscle (GFSM). Tension changes were isometrically measured, and the mRNA expression of prostanoid receptors was measured by RT‐qPCR. DHA and EPA significantly inhibited contractions induced by the prostanoids and U46619, whereas LA inhibited those induced by prostaglandin D 2 and U46619. The mRNA expression levels of the prostanoid receptors were TP ≈ EP 3 >> FP > EP 1 . The inhibition by DHA, EPA, and LA was positively correlated with that by SQ 29,548 (a TP receptor antagonist) but not with that by L‐798,106 (an EP 3 receptor antagonist). DHA and EPA suppressed high KCl‐induced contractions by 35% and 25%, respectively, and the contractions induced by the prostanoids and U46619 were suppressed by verapamil, a voltage‐dependent Ca 2+ channel (VDCC) inhibitor, by 40%–85%. Although LA did not suppress high KCl‐induced contractions, it suppressed U46619‐induced contractions in the presence of verapamil. However, LA did not show significant inhibitory effects on U46619‐induced Ca 2+ increases in TP receptor‐expressing cells. In contrast, LA inhibited U46619‐induced contractions in the presence of verapamil, which was also suppressed by SKF‐96365 (a store‐operated Ca 2+ channel [SOCC] inhibitor). These findings suggest that the TP receptor and VDCC are targets of DHA and EPA to inhibit prostanoid‐induced contractions of guinea pig GFSM, and SOCCs play a significant role in LA‐induced inhibition of U46619‐induced contractions.

An 80-year-old man presented with painful swelling in the mandibular region and fistula with pus discharge that developed after tooth extractions. He had taken oral alendronate sodium hydrate and prednisolone for osteoporosis for five years. The lesion was diagnosed as bisphosphonate-related osteonecrosis of the jaw. FDG-PET revealed a high accumulation of FDG in the right mandibular region. The patient underwent hyperbaric oxygen therapy twenty times. FDG-PET SUVmax drastically decreased from 5.6 to 1.8 after hyper baric oxygen therapy, paralleling the change in clinical symptoms, while other modalities did not show remarkable changes. This is the first study demonstrating the utility of FDG-PET in monitoring hyper baric oxygen therapy for bisphosphonate-related osteonecrosis of the jaw

Background Even if 3D angiographic images of preoperative contrast-enhanced computed tomography (CT) are created, the coronal and axial sections can be unclear, and thus, it is difficult to achieve projection awareness similar to that of actual laparoscopic images. In recent years, the technology of analyzing and applying medical images has advanced, and surgical simulation and navigation have been widely used to improve the safety of surgical operations. It is important to understand pelvic anatomy in the area of rectal cancer, and use of the SYNAPSE VINCENT makes it possible to simulate the anatomy before surgery, which is very useful in educating surgeons and their assistants. Materials and methods An important objective in surgery is to understand the anatomy of the external/internal iliac arteries and lymph nodes in lateral lymph node dissection (LLD) for rectal cancer. In this study, we explored the accuracy and usefulness of SYNAPSE VINCENT images of pelvic anatomy (especially vascular anatomy) analyzed preoperatively in two cases of LLD for rectal cancer in our department. Results The patients were two men aged 73 and 57 years, respectively. Both patients underwent robotic abdominal perineal resection and LLD with neoadjuvant chemoradiotherapy. The operating times for LLD were 138 and 106 min, estimated blood loss was less than 10 mL and 20 mL, and the harvested lymph nodes were nos. 21 and 22, respectively. The SYNAPSE VINCENT could be used for simulation and navigation before and during surgery. For experienced surgeons, the system helped them carry out operations more accurately. Conclusion In the future, surgical support using virtual reality, augmented reality, and mixed reality based on medical images will be useful and is expected to improve the safety, accuracy, and efficiency of surgery, which is extremely useful for both young and skilled surgeons preparing for difficult operations.

Background/Aim: Prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) indicate nutritional status and host immunity. We used immunohistochemistry and apparent diffusion coefficient (ADC) values calculated using diffusion-weighted imaging (DWI) to investigate relationships of these factors with pathological and radiological characteristics in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT). Patients and Methods: We evaluated expression levels of VEGFA, CD8, CD33, and ADC values in tumors pre/post nCRT; and analyzed the relationships between those factors and PNI, NLR in 32 patients. Results: Pretreatment PNI negatively correlated with change in tumor stromal CD8+ T cells and positively correlated with ADC values. Pretreatment NLR and PNI change correlated with recurrence-free survival (RFS). Conclusion: Patients with higher pretreatment PNI had greater changes in ADC values and stromal CD8+ T-cell counts, and those with greater PNI reduction from nCRT had a worse prognosis. Proper nutritional management during nCRT benefits patients and may lead to better prognosis in rectal cancer.