MiR-30a-5p inhibits cell behaviors in esophageal cancer via modulating CBX2.

BACKGROUND: This investigation studied the impacts of the miR-30a-5p/CBX2 axis on esophageal cancer (EC). METHODS: Research objects were ascertained using The Cancer Genome Atlas database. Followed by qRT-PCR, western blot, dual-luciferase reporter, MTT, Transwell, and wound healing approaches, we tested gene expression and varying cell behaviors RESULTS: Conspicuously miR-30 family members (miR-30a-5p, miR-30b-5p, miR-30c-5p, miR-30d-5p, miR-30e-5p) downregulation and CBX2 upregulation were discovered in EC cells. miR-30 family members target CBX2 and inhibited CBX2 expression. EC cell behaviors were inhibited by miR-30a-5p/CBX2 axis. CONCLUSION: MiR-30a-5p draws a new inspiration for EC treatment.

Hyperprogression After Immunotherapy for Primary Small Cell Neuroendocrine Carcinoma of the Ureter: A Case Report.

BACKGROUND: Primary small cell neuroendocrine carcinoma (SCNEC) in the ureter is extremely rare and has been sporadically reported in case reports. Its incidence, diagnosis, treatment, and outcomes have not yet been thoroughly understood. Here we present a patient with advanced SCNEC in the ureter who was treated by multimodal strategies. To the best of our knowledge, this is the first literature report about the clinical outcomes of the combination of programmed death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) and radiotherapy in patient with primary ureteral SCNEC. CASE PRESENTATION: A 71-year old male presented with right flank pain and gross hematuria. A laparoscopic right nephroureterectomy was performed. He was diagnosed with primary ureteral SCNEC, pT3N0M0. Following the surgery, 4 cycles of adjuvant chemotherapy with carboplatin and etoposide (CE) were administered, with disease-free survival (DFS) of 10.1 months. He was then offered 4 cycles of palliative first-line chemotherapy with nedaplatin and irinotecan. The disease was continuously progressed, with progression-free survival (PFS) of 3.7 months. The patient subsequently received second-line treatment with PD-L1 ICI combined with radiotherapy. Unfortunately, hyperprogressive disease was found at the end of treatment. MRI and CT scan showed bilateral pubic bones, right acetabulum, and liver metastases. Without further intervention, the patient died from extensive metastatic disease 2 months after diagnosis, with overall survival (OS) of 18.2 months. CONCLUSION: Physicians must be aware of this rare and aggressive carcinoma at its initial presentation. Special attention should be paid to the potential likelihood of hyperprogression during the treatment.

Long-Term Results of Concurrent Chemoradiotherapy Combined with Anti-EGFR Monoclonal Antibody Prior to Surgery in Locally Advanced Cervical Cancer: A Single-Institute Prospective Study.

PURPOSE: We aimed to evaluate the long-term survival outcomes of concurrent chemoradiotherapy (CCRT) combined with nimotuzumab followed by surgery in patients with locally advanced cervical cancer (LACC). PATIENTS AND METHODS: Patients received whole pelvic intensity-modulated radiation therapy (IMRT) and concomitantly with weekly cisplatin (40 mg/m2) or nedaplatin (30 mg/m2) and weekly nimotuzumab (200 mg). After assessment of the treatment response, patients then underwent radical surgery. RESULTS: Between June 2013 and July 2016, 33 patients with FIGO IB2-IIIB cervical cancer were recruited. Clinical complete response and partial response were observed in 8 (24.3%) and 23 patients (69.7%), respectively. Twenty-seven patients (81.8%) were successfully treated with radical hysterectomy and pelvic lymphadenectomy: 9 (33.3%) showed pathological complete response; 10 (37.1%) showed partial response and 8 (29.6%) presented with persistent macroscopic/microscopic residual carcinoma. For the intention-to-treat population, the median follow-up time was 53.7 months. Locoregional recurrence and distant metastases were observed in three and seven patients, respectively. The 5-year overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival were 81.5%, 72.7%, 90.9%, and 78.3%, respectively. Both acute and late toxicities were manageable and mainly limited to grade 1 or 2. CONCLUSION: Concurrent chemoradiotherapy combined with nimotuzumab followed by surgery for patients with LACC is safe and results in excellent long-term treatment outcomes. Further randomized controlled studies are warranted to confirm the findings.

Cancer associated fibroblasts-derived exosomes contribute to radioresistance through promoting colorectal cancer stem cells phenotype.

Radioresistance observed in patients with colorectal cancer (CRC) may be related to the presence of cancer stem cells (CSCs), but the underlying mechanism(s) remain unclear. Cancer-associated fibroblasts (CAFs) can regulate the stemness of cancer cells and tumor radiosensitivity. In addition, exosomes have been reported to modify treatment response by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from CAFs (CAF-exosomes) are involved in mediating resistance to radiotherapy in colorectal cancer and to explore the underlying mechanism. We found that CSCs were inherently resistant to cell death induced by radiotherapy. CAF-derived CM promoted clonogenicity and radioresistance of CRC cells. Further investigations revealed that exosomes isolated from CM induced the above effects whereas exosome-depleted CM (solution) was not able to induce clonogenicity and radioresistance. Finally, exosomes could activate transforming growth factor-ß (TGF-ß) signaling pathway and TGFß1-neutralizing antibody inhibit this effect and decrease clonogenicity and expression levels of stemness genes. In conclusion,our findings suggest CAFs promote stemness of CRC cells and thus increase radiation resistance. Exosomes derived from CAFs play a crucial role through activating TGF-ß signaling pathway in this process.