Neoadjuvant immunotherapy combined with chemotherapy in the treatment of stage III lung squamous cell carcinoma: a retrospective cohort study.

Background: Neoadjuvant immunochemotherapy has been proven to be a successful therapeutic strategy for patients with locally advanced non-small cell lung cancer (NSCLC). Nevertheless, there is a paucity of information regarding surgical feasibility and safety as well as tumor response. The present study aimed to investigate the therapeutic and surgical outcomes for patients with stage III lung squamous cell carcinoma (LSCC). Methods: Patients with stage III potentially resectable LSCC treated with neoadjuvant immunochemotherapy at The First Affiliated Hospital of Ningbo University between March 2020 and June 2022 were retrospectively included. Oncologic outcomes and intraoperative and postoperative variables were assessed. Results: A total of 17 locally advanced LSCC patients were included in the study. Patients in stages IIIA and IIIB were represented by 10 (58.8%) and 7 (41.2%) cases, respectively. A minimally invasive procedure was successfully completed in 12 out of 17 cases (70.6%). A total of 10 patients (58.8%) had standard lobectomies performed, 1 (5.9%) had a bilobectomy, 3 (17.6%) had pneumonectomies, and 1 (5.9%) had a wedge resection. A total of 7 patients (41.2%) experienced postoperative complications, and there were no 30- or 90-day mortalities. The 2-year disease-free survival (DFS) and overall survival (OS) rates were 76.6% and 82.5%, respectively. The rate of major pathological response (MPR) was 70.6%. Conclusions: Lung resection after immunochemotherapy for potentially resectable stage III LSCC is feasible and safe. This treatment strategy results in a significant pathologic response and promising rates of OS at 2 years.

Deletion of osteopontin in non-small cell lung cancer cells affects bone metabolism by regulating miR-34c/Notch1 axis: a clue to bone metastasis.

Lung cancer is prone to bone metastasis, and osteopontin (OPN) has an important significance in maintaining bone homeostasis. The goal of this study was to explore the impact of OPN level on bone metabolism and the molecular mechanism of inhibiting bone metastasis in non-small cell lung cancer (NSCLC). The expression of OPN in NSCLC was ascertained by Western blot and immunohistochemistry, and the correlation between the expression level of OPN and survival of patients was analyzed. Then the shRNA technology was applied to reduce the expression of OPN in NSCLC cells, and CCK-8 assay was carried out to investigate the effect of low expression of OPN on the proliferation of NSCLC cells. In addition, the effects of low expression of OPN on osteoclast differentiation, osteoblast generation and mineralization were studied using osteoclast precursor RAW264.7 and human osteoblast SaOS-2 cells, and whether OPN could regulate miR-34c/ Notch pathway to affect bone metabolism was further explored. The findings showed that the high level of OPN in NSCLC was closely related to the poor prognosis of patients and the abnormal proliferation of NSCLC cell lines. The suppression of OPN was beneficial to inhibit the differentiation of osteoclasts and promote the mineralization of osteoblasts. Besides, this study confirmed that the deletion of OPN can regulate bone metabolism through the regulation of miR-34c/Notch1 pathway, which will contribute to inhibiting the occurrence of osteolytic bone metastasis in NSCLC.

Treatment paradigms and survival outcomes in esophageal adenocarcinoma with liver metastasis: a retrospective cohort study using the SEER database.

Background: Esophageal adenocarcinoma with liver metastasis (EACLM) at the time of diagnosis has a poor prognosis and few therapeutic options. The best treatment options and prognostic factors for EACLM patients are unclear. The present study sought to explore the optimal treatment modalities for and the prognosis of these patients. Methods: Patients diagnosed with EACLM at the time of diagnosis were identified from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2015. The last follow-up date was December 31, 2018. Treatment patterns were divided into four groups: local therapy (surgery/radiation), systemic therapy [chemotherapy (CT)], combination therapy (surgery/radiation + CT), and no treatment. The Kaplan-Meier (K-M) method and log-rank test were used for overall survival (OS) and disease-specific survival (DSS). Univariable and multivariable Cox regression were performed to identify the prognostic factors. Propensity score-matching (PSM) analyses were performed for sensitive analyses. Results: A total of 925 patients diagnosed with EACLM were included in the study. The median OS was 12, 10, 3, and 2 months for combination therapy, systemic therapy, local therapy, and no treatment, respectively (P<0.001). After PSM, the patients who received systemic treatment had a better OS (median 9 vs. 2 months; P<0.001) and DSS (median 9 vs. 3 months; P<0.001) than those who received no treatment. Compared to systemic therapy, combination therapy did not increase patients' OS (median 13 vs. 12 months, P=0.069) but did improve their DSS (median 19 vs. 13 months, P=0.048). Conclusions: EACLM patients might benefit the most from systemic therapy and combination therapy. For patients who are well-tolerated, combination therapy should be considered as a preferable option.

C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C motif chemokine receptor 7(CXCR7) regulates epithelial-mesenchymal transition process and promotes the metastasis of esophageal cancer by activating signal transducer and activator of transcription 3 (STAT3) pathway.

Esophageal cancer is a malignant tumor of the digestive system that is prone to metastasis. Chemokines and their receptors act an essential role in the occurrence and development of tumors. Here, we investigated the regulatory mechanism of CXCL12/CXCR7 in the growth and metastasis of esophageal cancer. CXCR7 was found highly expressed in clinical tissues and cells of esophageal cancer. Knockdown of CXCR7 inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process of esophageal cancer cells. The knockdown of chemokine CXCL12 also inhibited the expression of EMT-related proteins and the mesenchymal morphology changes of esophageal cancer cells, but the knockdown of C-X-C motif chemokine receptor 4 (CXCR4) had no such effect. Furthermore, the knockdown of CXCR7 attenuated the enhanced EMT process induced by CXCL12 overexpression, while the knockdown of CXCR4 cannot inhibit this process. In addition, overexpressed CXCL12/CXCR7 activated the downstream STAT3 pathway, but had little effect on the extracellular regulated protein kinase (ERK) or serine-threonine kinase (AKT) pathways. Inhibition of the STAT3 pathway using AZD9150 weakened the accelerated effects of CXCL12/CXCR7 on the growth and metastasis of esophageal cancer in vitro and in vivo. In conclusion, our research revealed that CXCL12/CXCR7 regulates EMT and other malignant processes by activating the STAT3 pathway to accelerate the growth and metastasis of esophageal cancer.