Zoledronic acid is the most potent osteoclast inhibitor and is widely used for advanced cancer patients with bone metastasis, but its role on cancer stem cells (CSCs) remains unclear. In the present study, we aimed to identify the stemness phenotypic characteristics of CSCs derived from cervical cancer cells and explore the anti-cancer efficiency of zoledronic acid on these cells, as well as the possible molecular mechanisms. Stemness phenotypic identification of cervical cancer cells derived CSCs was performed via sphere formation efficiency (SFE), tumorigenesis, immunofluorescence staining, Transwell assay, and western blot. Anti-cancer efficiency of zoledronic acid on these cells (including proliferation, stemness phenotype, apoptosis, and cell cycle) was carried out through MTT assay, SFE, transwell, DAPI staining, flow cytometry, immunofluorescence, TUNEL staining, and western blot, both in vitro and in vivo. Enhanced self-renewal ability, including SFE and tumorigenesis, was verified in cervical cancer cells derived CSCs compared to parental cervical cancer cells. Specifically, the expression of ALDH1, Sox2, CD49f, Nanog, and Oct4 was significantly up-regulated in cervical cancer cells derived CSCs. Furthermore, enhanced migratory ability was observed in these cells along with up-regulated N-cadherin and Vimentin and down-regulated E-cadherin. Zoledronic acid inhibited cervical cancer cells derived CSCs proliferation in vitro and in vivo. The stemness phenotype of these CSCs including tumor sphere formation, migration, as well as the expression of the aforementioned associated markers was also suppressed. In addition, zoledronic acid significantly induced apoptosis and cell cycle arrest of cervical cancer cells derived CSCs in a dose-dependent manner. Mechanistically, the expression of phosphorylated Erk1/2 and Akt was significantly increased in cervical cancer cells derived CSCs compared to parental cervical cancer cells. Zoledronic acid inhibited phosphorylated Erk1/2 and Akt in cervical cancer cells derived CSCs. IGF-1, a potent stimulator for Erk1/2 and PI3K/Akt, attenuated the aforementioned anti-cancer effect of zoledronic acid. Zoledronic acid inhibited the growth of cervical cancer cells derived CSCs through attenuating their stemness phenotype, inducing apoptosis, and arresting cell cycle. The suppression of phosphorylated Erk1/2 and Akt was involved in this process.

The vast majority of cancer-related deaths are attributed to metastasis. The lung, being a common site for cancer metastasis, is highly prone to being a target for multiple cancer types and causes a heavy disease burden. Accumulating evidence has demonstrated that tumor metastasis necessitates continuous interactions between tumor cells and distant metastatic niches. Nevertheless, a comprehensive elucidation of the underlying mechanisms governing lung-specific metastasis still poses a formidable challenge. In this review, we depict the lung susceptibility and the molecular profiles of tumors with the potential for lung metastasis. Under the conceptual framework of “Reciprocal Tumor-Lung Metastatic Symbiosis” (RTLMS), we mechanistically delineate the bidirectional regulatory dynamics and coevolutionary adaptation between tumor cells and distal pulmonary niches during lung-specific metastasis, including the induction of pre-metastatic-niches, positive responses of the lung, tumor colonization, dormancy, and reawakening. An enhanced understanding of the latest mechanisms is essential for developing targeted strategies to counteract lung-specific metastasis.

Nasopharyngeal carcinoma (NPC) is a common malignancy in China and Southeast Asia. Radiotherapy is the major treatment modality for patients with NPC, but does not always achieve fully satisfactory outcomes. Studies have shown that epidermal growth factor receptor (EGFR) is highly expressed in NPC, and EGFR-targeted treatment is expected to be a new strategy for NPC. Recently, clinical trials have shown that NPC patients have different responses to gefitinib. Thus, the identification of indicators that can regulate and predict the sensitivity of NPC to gefitinib is very valuable. MiRNAs (MicroRNAs) are closely related to cancer development. We studied miRNAs in NPC cell lines to identify those that can regulate and predict the effectiveness of gefitinib on NPC. CCK8, Annexin V-FITC assays and animal models were carried out to evaluate the inhibitory effect of gefitinib on NPC cell lines HNE-1 and HK-1. MiRNA microarrays were used to detect and compare the miRNAs expression levels in the two cells with gefitinib or not, and qRT-PCR was used to evaluate miR-125a-5p expression in NPC cells and in serum of the tumor animal models. Loss-of-function and gain-of-function experiments were taken to evaluate the effect of miR-125a-5p on gefitinib effectiveness. Western blots were used to evaluate the effect of miR-125a-5p on p53 and Her2 in HNE-1 and HK-1 cells. Gefitinib inhibited two NPC cell lines proliferation in vitro and in vivo,and HNE-1 cells were less sensitive than HK-1 cells to gefitinib.MiR-125a-5p expression levels were increased by geftinib in the two cell lines and in the serum of NPC tumor bearing-mice. This phenomenon was weak in HNE-1 cells and strong in HK-1 cells. MiR-125a-5p over expression improved anti-proliferative and pro-apoptotic effects of gefitinib on the NPC cells and that miR-125a-5p down-regulation decreased those effects. MiR-125a-5p also increased p53 protein expression in HNE-1 cells, and decreased Her2 protein expression in HNE-1 and HK-1 cells. Our results indicate that gefitinib sensitivity and some miRNAs expressions varied in NPC cell lines. The miR-125a-5p is a possible candidate that can regulate and predict the effect of gefitinib on NPC.

Distal gastrectomy (DG) with lymph node dissection for gastric cancer is routinely performed. In this meta-analysis, we present an updated overview of the perioperative and oncological outcomes of laparoscopic DG (LDG) and robotic DG (RDG) to compare their safety and overall outcomes in patients undergoing DG. An extensive search was conducted using the MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials from the establishment of the database to June 2023 for randomized clinical trials comparing RDG and LDG. The primary outcome was operative results, postoperative recovery, complications, adequacy of resection, and long-term survival. We identified twenty studies, evaluating 5,447 patients (1,968 and 3,479 patients treated with RDG and LDG, respectively). We observed no significant differences between the two groups in terms of the proximal resection margin, number of dissected lymph nodes, major complications, anastomosis site leakage, time to first flatus, and length of hospital stay. The RDG group had a longer operative time (P < 0.00001), lesser bleeding (P = 0.0001), longer distal resection margin (P = 0.02), earlier time to oral intake (P = 0.02), fewer overall complications (P = 0.004), and higher costs (P < 0.0001) than the LDG group. RDG is a promising approach for improving LDG owing to acceptable complications and the possibility of radical resection. Longer operative times and higher costs should not prevent researchers from exploring new applications of robotic surgery. (c) 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).

Liver metastases (LMs) are common in lung cancer. Despite substantial advances in diagnosis and treatment, the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system. The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research. Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells. Overall, these microenvironments create pre- and post-metastatic conditions for the progression of LMs. Herein, we reviewed the epidemiology, physiology, pathology and immunology, of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis. Additionally, we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations. These approaches target liver elements as the basis for future clinical trials, including combinatorial interventions reported to resolve hepatic immune suppression, such as immunotherapy plus chemotherapy, immunotherapy plus radiotherapy, immunotherapy plus anti-angiogenesis therapy, and surgical resection.