Efficacy and Safety Aiming at the Combined-Modality Therapy of External Beam Radiotherapy (40Gy) and Iodine-125 Seed Implantation for Locally Advanced NSCLC in the Elderly.

PURPOSE: To evaluate the efficacy and safety of combined-modality therapy for elderly patients with locally advanced non-small-cell lung cancer (NSCLC) invading the chest wall. PATIENTS AND METHODS: We retrospectively enrolled 21 elderly patients (aged ≥60 years) with locally advanced NSCLC invading the chest wall. For external beam radiotherapy (EBRT) of the primary tumor, 40Gy was applied and supplemented with iodine-125 seed implantation while 60Gy was applied to the lymph nodes of the mediastinum. Follow-up was conducted every 3 months postoperatively. The related analytic parameters were change in tumor size, the objective response rate (ORR), the disease control rate (DCR), the degree of pain relief, the improvement of physical status, and toxicity. RESULTS: The combined-modality therapy significantly inhibited local growth of the tumor (from 7.84±1.20 to 4.69±1.90 cm) (P <0.0001), with 71.4% ORR and 90.5% DCR at 1 year. The cancer-related pain was significantly relieved (P <0.05) and physical status was significantly improved (P <0.05). No procedure-associated death or grade > 2 irradiation-related adverse effects were reported in this study. CONCLUSION: The combined-modality therapy of EBRT with 40Gy and permanent iodine-125 seed implantation is an efficacious and safe treatment option for elderly patients with locally advanced NSCLC invading the chest wall.

STAT1-induced upregulation of lncRNA KTN1-AS1 predicts poor prognosis and facilitates non-small cell lung cancer progression via miR-23b/DEPDC1 axis.

Several of the thousands of long noncoding RNAs (lncRNAs) have been functionally characterized in various tumors. In this study, we aimed to explore the function and possible molecular mechanism of lncRNA KTN1 antisense RNA 1 (KTN1-AS1) involved in non-small cell lung cancer (NSCLC). We identified a novel NSCLC-related lncRNA, KTN1 antisense RNA 1 (KTN1-AS1) which was demonstrated to be distinctly highly expressed in NSCLC. KTN1-AS1 upregulation was induced by STAT1. Clinical study also suggested that higher levels of KTN1-AS1 were associated with advanced clinical progression and a shorter five-year overall survival. Functionally, loss-of-function assays with in vitro and in vivo experiments revealed that KTN1-AS1 promoted the proliferation, migration, invasion and EMT progress of NSCLC cells, and suppressed apoptosis. Mechanistic studies indicated that miR-23b was a direct target of KTN1-AS1, which functioned as a ceRNA to subsequently facilitate miR-23b's target gene DEPDC1 expression in NSCLC cells. Rescue experiments confirmed that KTN1-AS1 overexpression could increase the colony formation and migration ability suppressed by miR-23b upregulation in NSCLC cells. Overall, our findings imply that STAT1-induced upregulation of KTN1-AS1 display tumor-promotive roles in NSCLC progression via regulating miR-23b/DEPDC1 axis, suggesting that KTN1-AS1 may be a novel biomarker and therapeutic target for NSCLC patients.

Microwave ablation plus chemotherapy versus chemotherapy in advanced non-small cell lung cancer: a multicenter, randomized, controlled, phase III clinical trial.

OBJECTIVES: This prospective trial was performed to verify whether microwave ablation (MWA) in combination with chemotherapy could provide superior survival benefit compared with chemotherapy alone. MATERIALS AND METHODS: From March 1, 2015, to June 20, 2017, treatment-naïve patients with pathologically verified advanced or recurrent non-small cell lung cancer (NSCLC) were randomly assigned to MWA plus chemotherapy group or chemotherapy group. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), time to local progression (TTLP), and objective response rate (ORR). The complications and adverse events were also reported. RESULTS: A total of 293 patients were randomly assigned into the two groups. One hundred forty-eight patients with 117 stage IV tumors were included in the MWA plus chemotherapy group. One hundred forty-five patients with 113 stage IV tumors were included in the chemotherapy group. The median follow-up period was 13.1 months and 12.4 months, respectively. Median PFS was 10.3 months (95% CI 8.0-13.0) in the MWA plus chemotherapy group and 4.9 months (95% CI 4.2-5.7) in the chemotherapy group (HR = 0.44, 95% CI 0.28-0.53; p < 0.0001). Median OS was not reached in the MWA plus chemotherapy group and 12.6 months (95% CI 10.6-14.6) in the chemotherapy group (HR = 0.38, 95% CI 0.27-0.53; p < 0.0001) using Kaplan-Meier analyses with log-rank test. The median TTLP was 24.5 months, and the ORR was 32% in both groups. The adverse event rate was not significantly different in the two groups. CONCLUSIONS: In patients with advanced NSCLC, longer PFS and OS can be achieved with the treatment of combined MWA and chemotherapy than chemotherapy alone. KEY POINTS: • Patients treated with MWA plus chemotherapy had superior PFS and OS over those treated with chemotherapy alone. • The ORR of patients treated with MWA plus chemotherapy was similar to that of those treated with chemotherapy alone. • Complications associated with MWA were common but tolerable and manageable.

Upregulation of syncytin-1 promotes invasion and metastasis by activating epithelial-mesenchymal transition-related pathway in endometrial carcinoma.

BACKGROUND: Endometrial carcinoma (EC) is the most common and lethal malignancy worldwide. Syncytin-1 is expressed in multiple types of cancer. However, the expression pattern and potential mechanism of syncytin-1 and its clinical significance in EC remain unclear. MATERIALS AND METHODS: We analyzed 130 primary EC specimens from Binzhou Medical University to investigate the clinical role of syncytin-1 in EC by using different advanced pathological stages of EC tissues. Kaplan-Meier analysis was used to measure the overall survival of EC patients. Syncytin-1 expression was analyzed by Western blot assays in HECCL-1 and RL-95-2 cells. Cell proliferation, cycle, migration, and invasion abilities were detected by cell counting kit-8, flow cytometry, and transwell assays. AKT and epithelial-mesenchymal transition (EMT)-related genes were assessed by Western blot assays in HECCL-1 and RL-95-2 cells. RESULTS: Syncytin-1 was upregulated in EC tissues and cells and was related to clinical stages, expression of ER, Ki-67, and overall survival of EC. Functional research revealed that overexpression of syncytin-1 can promote cell proliferation, cell cycle progression, and the migration and invasion of EC cells. Suppression of syncytin-1 expression also inhibited cell proliferation and apoptosis in vitro. The expression of syncytin-1 substantially improved the expression levels of EMT-related genes (vimentin, E-cadherin, slug, and ZEB1) but significantly decreased those of epithelial markers (N-cadherin and snail). In addition, we found that syncytin-1 was not correlated with AKT-related genes (total-AKT, p-AKT, and vinculin). CONCLUSION: Our results suggested that syncytin-1 may promote aggressive behavior and can serve as a novel prognostic biomarker for EC. Our study provides new insights into the regulatory mechanism of EMT signaling.

Microwave ablation for lung cancer patients with a single lung: Clinical evaluation of 11 cases.

BACKGROUND: The study was conducted to retrospectively evaluate the safety and effectiveness of computed tomography (CT)-guided percutaneous microwave ablation (MWA) for peripheral non-small cell lung cancer (NSCLC) in 11 patients with a single lung after pneumonectomy. METHODS: From May 2011 to March 2015, 11 single-lung patients (8 men and 3 women; mean age 60.3 years, range 46-71) with peripheral NSCLC underwent 12 sessions of MWA. Eleven tumors measuring 13-52 mm (mean 30.2 mm) were treated. Follow-up was performed via CT scan at 1, 3, 6, 12, 18, and 24 months after the procedure and annually thereafter. Clinical outcomes were evaluated and complications after MWA were summarized. RESULTS: At a median follow-up period of 20 months (range 6-38), four patients showed evidence of local recurrence at a rate of 36.4% (4/11). Median overall survival was 20 months. The overall survival rates at one, two, and three years after MWA were 88.7%, 63.6%, and 42.3%, respectively. Complications after MWA included pneumothorax (33.3%), hemoptysis (33.3%), intrapulmonary bleeding (25%), pleural effusion (16.7%), and pulmonary infection (8.3%). None of the patients died during the procedure or in the 30 days after MWA. CONCLUSION: CT-guided percutaneous MWA is safe and effective for the treatment of peripheral NSCLC in patients with a single lung after prior pneumonectomy.

Medulloblastoma with soft-tissue and skeletal metastases in an adult: A case report.

Medulloblastoma (MB) is a highly malignant primary brain tumor, which occurs in the cerebellum or posterior cranial fossa. MB is most commonly identified in children <10 years of age. The disease is rare in adults, affecting patients aged between 30 and 50 years of age, with an incidence of 0.5 cases per 1,000,000 individuals. Extraneural metastases are reported in 7-10% of cases, most commonly involving the bones and more rarely involving the lymph nodes, visceral organs and bone marrow. The current study presents the case of a 36-year-old male who underwent a gross total resection followed by radiation therapy to the craniospinal axis for the treatment of MB. The patient subsequently developed widespread metastasis, which involved the soft tissue of the occipital bone. Subsequently, the patient was administered palliative radiotherapy and initially exhibited a good clinical response. However, the patient succumbed at 18 months post-diagnosis due to dissemination of the disease. The literature on the extraneural metastasis of MB is also reviewed in the current study.

MiR-34a Inhibits Viability and Invasion of Human Papillomavirus-Positive Cervical Cancer Cells by Targeting E2F3 and Regulating Survivin.

OBJECTIVE: Previous studies confirmed that high-risk human papillomavirus (HR-HPV) infection is a risk factor of cervical cancer, and the infection was associated with significantly reduced miR-34a expression during carcinogenesis. However, the downstream targets of miR-34a and their roles are still not well understood. This study explored the regulative role of miR-34a on E2F3 and survivin expression and the viability and invasion of HPV-positive cervical cancer cells. METHODS: MiR-34a and survivin expression in 56 cases of HR-HPV-positive patients, 28 cases of HR-HPV-negative patients, and 28 normal cases without HR-HPV infections were measured. Human papillomavirus-18-positive HeLa cervical cancer cells and HPV-16-positive SiHa cells were used to explore the effect of miR-34a on cell viability and invasion. The molecular target of miR-34a was also explored in cervical cancer cells. RESULTS: The results showed that miR-34a overexpression could inhibit HPV-positive cancer cell viability, whereas its downregulation promoted cell viability. E2F3 is a direct target of miR-34a in HPV-positive cervical cancer cells. By targeting E2F3, miR-34a could regulate the expression of survivin. Thus, through regulating E2F3 and survivin, miR-34a could reduce the viability and invasion of HPV-positive cervical cancer cells. CONCLUSIONS: This study confirmed a novel miR-34a-E2F3-survivin axis in the tumor suppressor role of miR-34a in cervical cancer.

A phase II study of preoperative chemotherapy with modified FOLFOX6 followed by surgery and postoperative chemoradiation in patients with localized gastric adenocarcinoma.

The optimal neoadjuvant and adjuvant treatment for gastric cancer remains controversial. We conducted a phase II study using preoperative chemotherapy with modified FOLFOX6 followed by surgical resection and postoperative chemoradiation in patients with gastric carcinoma. Preoperative chemotherapy (two or three cycles) consisted of a 2-h infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46-h continuous infusion of 5-fluorouracil (5-FU; 2,400 mg/m2). Surgical resection was planned 4 weeks after the last chemotherapy cycle. Patients underwent postsurgical chemoradiation, receiving a total dose of 45 Gy and 5-FU continuous infusion (350 mg/m2/day). The primary end points were feasibility, overall response rate, and R0 resectability rate after preoperative chemotherapy. The secondary end points were tolerability, treatment-associated complications, disease-free survival, and overall survival. Nineteen patients were enrolled in this study. After neoadjuvant treatment, four patients (21.1%) experienced progressive disease, six patients (31.6%) showed partial remission, and nine patients (47.3%) showed stable disease. In 15 patients (78.9%) R0 resectability could be achieved. Eleven of these patients (73.3%) were able to undergo postoperative chemoradiation. Notably, eight (72.7%) of these patients were disease free and alive at median follow-up of 60 months. Chemotherapy associated neutropenia, neutropenic fever, and anastomotic dehiscence were observed. The combination of preoperative chemotherapy and postoperative chemoradiation is feasible in a significant subset of gastric cancer patients.