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Objective: Rare disease. Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine malignancy that has increased in incidence in recent decades. The management of MCC should involve multidisciplinary experts to achieve optimal patient outcomes. Radiotherapy is commonly used as adjuvant therapy. Our literature review of MCC indicates that aggressive adjuvant radiotherapy might have a positive impact on overall local control and survival. Case Reports: The first case is a 75-year-old male patient who discovered a right preauricular mass 2 weeks prior. He underwent right parotidectomy with tumor removal on 2012/07/09, and pathology revealed MCC in 3 lymph nodes. The patient received postoperative adjuvant radiotherapy (61.2 Gy) to the remaining right parotid tumor bed and right neck lymph nodes. The patient refused adjuvant chemotherapy. During long-term follow-up, the patient remained disease free for 10 years. The other case is a 73-year-old female patient with metastatic MCC in a left parotid lymph node. She also underwent left parotidectomy with tumor removal, and pathological staging performed according to the 8th edition of the AJCC staging system showed pTxN1aMx, stage IIIA. After the operation, she received postoperative adjuvant radiotherapy (56 Gy) to the remaining left parotid and left neck lymph nodes. The patient remained disease free for 14 months. Conclusions: Metastatic MCC of the parotid lymph nodes without a detectable primary skin tumor is very rare. Adjuvant radiotherapy to the tumor bed and regional nodal basin might be beneficial for preventing disease recurrence despite the absence of systemic medical therapy. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to compare the prognostic prediction performances of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th staging system and the Japan Esophageal Society (JES) 11th staging system for patients with esophageal squamous cell carcinoma who underwent radical (chemo) radiotherapy. Methods: In total, 574 patients were enrolled and categorized according to the tumor, node metastasis (TNM) AJCC/UICC 8th and JES 11th editions. Survival rates and disease-free survival were computed using the Kaplan–Meier technique. The log-rank test was used for survival difference analysis. Results: (1) The 8th AJCC/UICC N staging exhibited significant stratification for overall survival (OS) and progression-free survival (PFS). JES 11th showed significant OS stratification, but PFS was not well-stratified for N2–N4. (2) Both staging systems demonstrated significant stratification for OS and PFS. (3) AJCC/UICC 8th TNM staging yielded significantly well-stratified OS and PFS in the differing staging group. JES 11th failed to stratify OS and PFS for stages III and IVA. (4) AJCC/UICC 8th TNM stratified OS and PFS significantly well for lower and middle region tumors, whereas JES 11th inadequately stratified stages III and IVA. (5) Significant multivariable analysis results indicated that AJCC/UICC 8th independently predicted poor OS and PFS. Conclusions: In Chinese patients with esophageal squamous cell carcinoma who underwent radical (chemo) radiotherapy, the AJCC/ UICC 8th edition exhibited superior prognostic prediction capabilities compared with the JES 11th edition. [ABSTRACT FROM AUTHOR]

Purpose: To study the effect of overexpression of Rac1 on the radiosensitivity of transplanted nasopharyngeal carcinoma (NPC) in nude mice, and the mechanism involved. Methods: Forty Lucky SPF-grade male thymus-free nude mice were used. Mice were divided into 4 groups: overexpression control, overexpression Rac1, Rac1 inhibition, and inhibition control groups, each with 10 mice. The prepared cell lines were treated with 6 MV x-ray. Before and after radiation, the growth of tumors in each group was monitored. Histomorphological images of nude mice tumors were obtained using hematoxylin and eosin (H&E) stains. Protein expressions of p67, P47, and Rac1 were evaluated bu Western blotting. Results: Transplanted tumor growth slowed down after 20 days. Growth rate was significantly higher in Rac1 and Rac1 overexpression groups than in overexpression and inhibition control groups (p < 0.05). Overexpression of Rac1 resulted in more cell necrosis, incomplete cellular structure, severe nuclear fragmentation, nuclear pyknosis, and cytotoxic red staining in endoscopic tumor tissues (p < 0.05). There were significantly lower expression levels of p67, P47, and Rac1 in Rac1 invasion group than in invasion control and overexpression control groups, while the expression levels of p67 and P47 were significantly higher in overexpression Rac1 group and IR overexpression Rac1 group than in inhibition control (p < 0.05). However, concentrations of p67 and P47 were significantly higher in overexpression Rac1 and IR overexpression Rac1 groups than in inhibition control mice. Conclusion: Rac1 increases the radiosensitivity of NPC xenografts in nude mice via a mechanism related to the regulation of expressions of proteins associated with Rac1/NADPH signaling pathway. Thus, Rac1 is potentially a new target for radio-sensitization of NPC. [ABSTRACT FROM AUTHOR]

Immunogenic cell death (ICD) is essential for the activation of immune system against cancer. We aimed to investigate the efficacy of endoplasmic reticulum (ER)-associated protein degradation (ERAD) inhibitors (EerI and NMS-873) in enhancing radiation-induced ICD in esophageal cancer (EC). EC cells were administered with ERAD inhibitors, radiation therapy (RT), and the combination treatment. ICD hallmarks including calreticulin (CALR), adenosine triphosphate (ATP), and high mobility group protein B1 (HMGB1) were detected. The efficacy of ERAD inhibitors combined with RT in stimulating ICD was analyzed. Additionally, the role of ICD hallmarks in immune cell infiltration and patient survival was investigated. Inhibiting ERAD pathways was able to stimulate ICD component emission from dying EC cells in a dosedependent pattern. Radiation-induced ICD was significantly increased after high doses RT (≥10 Gy). ERAD inhibitor combined with moderate dose RT (≥6 Gy) was capable of stimulating increased ICD in EC cells. Dual therapy could elicit the antitumor immune response by enhancing dendritic cells maturation and phagocytosis. Further investigation revealed a significant correlation between CALR and tumorinfiltrating immune cells. Low expression of ATP and HMGB1 and high expression of CALR were associated with favorable survival in patients with EC. The immunogenicityof EC can be enhanced by ERAD inhibitors combined with moderate doses of RT. ICD hallmark genes, especially CALR, are correlated to immune cell infiltration and clinical outcomes in EC. The present results demonstrated an important method to improve the immunogenicity of EC cells for enhanced antitumor immune response. [ABSTRACT FROM AUTHOR]