N6-methyladenosine (m6A) is the most abundant epitranscriptome modification in mammalian mRNA. Recent years have seen substantial progress in m6A epitranscriptomics, indicating its crucial roles in the initiation and progression of cancer through regulation of RNA stabilities, mRNA splicing, microRNA processing and mRNA translation. However, by what means m6A is dynamically regulated or written by enzymatic components represented by methyltransferase-like 3 (METTL3) and how m6A is significant for each of the numerous genes remain unclear. We focused on METTL3 in pancreatic cancer, the prognosis of which is not satisfactory despite the development of multidisciplinary therapies. We established METTL3-knockdown pancreatic cancer cell line using short hairpin RNA. Although morphologic and proliferative changes were unaffected, METTL3-depleted cells showed higher sensitivity to anticancer reagents such as gemcitabine, 5-fluorouracil, cisplatin and irradiation. Our data suggest that METTL3 is a potent target for enhancing therapeutic efficacy in patients with pancreatic cancer. In addition, we performed cDNA expression analysis followed by gene ontology and protein-protein interaction analysis using the Database for Annotation, Visualization, and Integrated Discovery and Search Tool for the Retrieval of Interacting Genes/Proteins databases, respectively. The results demonstrate that METTL3 was associated with mitogen-activated protein kinase cascades, ubiquitin-dependent process and RNA splicing and regulation of cellular process, suggesting functional roles and targets of METTL3.

Objective: The objective of this study was to retrospectively analyse the treatment results of clinically localised angiosarcoma of the scalp and face. Methods: The records of 48 patients who were treated between 1987 and 2009 were reviewed. single modality or a combination of surgery, radiotherapy, chemotherapy and immunotherapy were administered. The median follow-up of all 48 patients was 13.7 months (range 2.5–105.9 months). Results: At the time of analysis, 45 of 48 patients (93.8%) had disease recurrences, and the lung was the most frequent site for recurrence (37 patients). In multivariate analysis, performance status (PS) and number of tumours were significant predictors of lung-metastasis-free (LMF) rate. For patients with multifocal tumours, chemotherapy use significantly decreased the LMF rate (p=0.0072). The 2-year actuarial overall survival (OS), progression-free survival and local control rates in all 48 patients were 22.1%, 10.7% and 46.3%, respectively. In multivariate analysis, PS, number of tumours, surgery and radiotherapy were significant prognostic factors for OS. Patients treated with both surgery and radiotherapy (2-year OS: 45.8%) had a significantly more favourable OS (p<0.0001) than patients treated with either surgery or radiotherapy (2-year OS: 11.1%) and patients treated with neither surgery nor radiotherapy (2-year OS: 0%). Conclusions: Our results indicated that PS and number of tumours were significant predictors for developing lung metastases. Our results also indicated that PS, number of tumours, surgery use and radiotherapy use were independent prognostic factors for OS. Multimodal treatments including surgery and radiotherapy were effective in improving OS for patients with these tumours. Advances in knowledge: Multimodal treatments including surgery and radiotherapy are effective in improving overall survival for patients with angiosarcoma of the scalp and face.

Mitochondrial pyruvate carrier (MPC) is known to cause different expressions in normal and cancer cells. We observed a change in phenotype with the suppression of MPC expression. We knocked down MPC1 and/or MPC2 using siRNA or shRNA. We observed its cell morphology and accompanying molecular marker. Furthermore, the radioresistance of the MPC knockdown cell line was examined using a colony formation assay. MPC1‐suppressed cells changed their morphology to a spindle shape. Epithelial‐mesenchymal transition (EMT) was suspected, and examination of the EMT marker by PCR showed a decrease in E‐cadherin and an increase in fibronectin. Focusing on glutamine metabolism as the mechanism of this phenomenon, we knocked down the glutamine‐metabolizing enzyme glutaminase (GLS). EMT was also observed in GLS‐suppressed cells. Furthermore, when MPC1‐suppressed cells were cultured in a glutamine‐deficient medium, changes in EMT markers were suppressed. In addition, MPC1‐suppressed cells also increased with a significant difference in radioresistance. Decreased MPC1 expression favorably affects EMT and radioresistance of cancer.

Chemoradiotherapy effectively treats superficial esophageal cancer and is optimal to preserve organs. However, late toxicity, particularly in cardiac diseases, obstructs clinical outcomes. We revealed the risk factors for cardiac event development post-chemoradiotherapy. Data from 80 patients who were diagnosed with submucosal invasive esophageal cancer without metastasis (confirmed using multiple modalities) and who underwent chemoradiotherapy between 2006 and 2014 were analyzed. Patients were 11% (9/80) female, and the median age and follow-up were 66.5 y and 73 mo, respectively. We calculated the individual radiation dose to the heart and analyzed relationships between the cardiac event occurrence rate and each clinical factor. The 5-y overall and recurrence-free survival rates were 74.6 and 62.4%, respectively. Among the total number of deaths, 34.6% was caused by esophageal cancer. During the follow-up, 13 patients developed severe cardiac events (ischemic heart diseases, n = 7; pericardial effusion, n = 3, atrial fibrillation, n = 1; and sudden death, n = 2). The significant risk factor for cardiac events post-chemoradiotherapy was the level of the heart’s exposure to radiation, with higher exposure associated with greater occurrence. History of smoking, obesity, comorbidity, and history of cardiac disease were unrelated to cardiac event occurrence post-chemoradiotherapy. Chemoradiotherapy is a favorable intervention for superficial esophageal cancer. Reducing the radiation dose to the heart likely contributes to preventing cardiac toxicity post-chemoradiotherapy.

The purpose of this study is to report our clinical outcomes using intensity-modulated radiation therapy (IMRT) for adjuvant treatment of cervical cancer, compared with three-dimensional conformal radiation therapy (3DCRT), in terms of tumor control, complications and dose-volume histogram (DVH) parameters. Between March 2008 and February 2014, 62 patients were treated with concurrent nedaplatin-based chemotherapy and whole-pelvic external beam radiation therapy (RT). Of these patients, 32 (52 %) received 3DCRT and 30 (48 %) received IMRT. The median follow-up periods were 40 months (range 2–74 months). The 3-year overall survival rate (OS), locoregional control rate (LRC) and progression-free survival rate (PFS) were 92, 95 and 92 % in the IMRT group, and 85, 82 and 70 % in the 3DCRT group, respectively. A comparison of OS, LRC and PFS showed no significant differences between IMRT and 3DCRT. The 3-year cumulative incidences of grade 2 or higher chronic gastrointestinal (GI) complications were significantly lower with IMRT compared to 3DCRT (3 % vs. 45 %, p < .02) and in patients with V40 of the small bowel loops of ≤340 mL compared to those with >340 mL (3 % vs. 45 %, p < .001). Patients treated with IMRT had a higher incidence of grade 3 acute hematologic complications (p < .05). V40 and V45 of the small bowel loops or bowel bag were predictive for development of both acute and chronic GI complications. Our results suggest that IMRT for adjuvant treatment of cervical cancer is useful for decreasing GI complications without worsening outcomes.

In radiotherapy treatment planning, intravenous administration of an iodine-based contrast agent during computed tomography (CT) improves the accuracy of delineating target volumes. However, increased tissue attenuation resulting from the high atomic number of iodine may result in erroneous dose calculations because the contrast agent is absent during the actual procedure. The purpose of this proof-of-concept study was to present a novel framework to improve the accuracy of dose calculations using dual-energy virtual unenhanced CT in the presence of an iodine-based contrast agent. Simple phantom experiments were designed to assess the feasibility of the proposed concept. By utilizing a “second-generation” dual-source CT scanner equipped with a tin filter for improved spectral separation, four CT datasets were obtained using both a water phantom and an iodine phantom: “true unenhanced” images with attenuation values of 2 ± 11 Hounsfield Units (HU), “enhanced” images with attenuation values of 274 ± 23 HU, and two series of “virtual unenhanced” images synthesized from dual-energy scans of the iodine phantom, each with a different combination of tube voltages. Two series of virtual unenhanced images demonstrated attenuation values of 12 ± 29 HU (with 80 kVp/140 kVp) and 34 ± 10 HU (with 100 kVp/140 kVp) after removing the iodine component from the contrast-enhanced images. Dose distributions of the single photon beams calculated from the enhanced images and two series of virtual unenhanced images were compared to those from true unenhanced images as a reference. The dose distributions obtained from both series of virtual unenhanced images were almost equivalent to that from the true unenhanced images, whereas the dose distribution obtained from the enhanced images indicated increased beam attenuation caused by the high attenuation characteristics of iodine. Compared to the reference dose distribution from the true unenhanced images, the dose distribution pass rates from both series of virtual unenhanced images were greater than 90%, while those from the enhanced images were less than approximately 50–60%. Dual-energy virtual unenhanced CT improves the accuracy of dose distributions in radiotherapy treatment planning by removing the iodine component from contrast-enhanced images.