Background: Esophageal squamous cell carcinoma (ESCC) is the sixth most lethal cancer worldwide and the fourth most lethal cancer in China. Genomic characterization of tumors, particularly those of different stages, is likely to reveal additional oncogenic mechanisms. Although copy number alterations and somatic point mutations associated with the development of ESCC have been identified by array-based technologies and genome-wide studies, the genomic characterization of ESCCs from different stages of the disease has not been explored. Here, we have performed either whole-genome sequencing or whole-exome sequencing on 51 stage I and 53 stage III ESCC patients to characterize the genomic alterations that occur during the various clinical stages of ESCC, and further validated these changes in 36 atypical hyperplasia samples. Results: Recurrent somatic amplifications at 8q were found to be enriched in stage I tumors and the deletions of 4p-q and 5q were particularly identified in stage III tumors. In particular, the FAM84B gene was amplified and overexpressed in preclinical and ESCC tumors. Knockdown of FAM84B in ESCC cell lines significantly reduced in vitro cell growth, migration and invasion. Although the cancer-associated genes TP53, PIK3CA, CDKN2A and their pathways showed no significant difference between stage I and stage III tumors, we identified and validated a prevalence of mutations in NOTCH1 and in the NOTCH pathway that indicate that they are involved in the preclinical and early stages of ESCC. Conclusions: Our results suggest that FAM84B and the NOTCH pathway are involved in the progression of ESCC and may be potential diagnostic targets for ESCC susceptibility.

Breast cancer is the most common malignancy and the second leading cause of cancer-related death in women. Recent studies have indicated that aberrant activation of Rho GTPases relates to the malignant properties of breast cancer cells. As the guanine nucleotide exchange factor of Rho GTPases, the role of ECT2 (epithelial cell transforming 2) in breast cancer is still unclear. Tissue microarrays and multiple public databases were utilized to investigate the relationship between ECT2 level and clinical-pathological features of breast cancer patients. Kaplan Meier-plotter online tool and tissue microarray with survival information were used to investigate the predictive value for breast cancer. Here, we found increased ECT2 level was highly associated with advanced TNM stage, poor differentiation, and loss of hormone receptors of breast cancer. Gene expression profile showed that ECT2 level was closely correlated to cell-proliferation-associated pathways. Integration analysis using public databases and tissue microarray indicated that high ECT2 was an adverse prognostic factor for breast cancer patients. We believe the ECT2 level might be a valuable complement for commercially available predictors such as the 21 genes test. Furthermore, ECT2 would be a novel target for drug development for breast cancer.

Nanomedicines receive great attention in cancer treatment. Nevertheless, nonbiodegradable and long-term retention still limit their clinical translation. Herein, we successfully synthesize a hypoxia-triggered degradable porphyrinic covalent organic framework (HPCOF) for antitumor therapy in vivo. HPCOF possesses wide absorption in near infrared region (NIR) which endows HPCOF excellent photothermal conversion efficiency and photoacoustic (PA) imaging ability. Moreover, HPCOF exhibits excellent photodynamic and photothermal effect under special-wavelength laser irradiation. For the first time, the in vitro and in vivo tests demonstrate that HPCOF shows effective therapeutic effect for the combination of PDT and PTT under the monitoring of PA imaging. Importantly, in tumor region, HPCOF could be triggered by hypoxia microenvironment and collapsed gradually, then cleared from the body after treatment. This work fabricates a novel COF for cancer treatment and testifies great potential of HPCOF in clinical application with reducing long-term toxicity.

Objective: A retrospective clinical study was conducted to compare the prognosis between the opioid analgesic (OA) treated and OA-untreated groups and to evaluate the effect of opioid analgesics on the efficacy of immune checkpoint inhibitors (ICIs) in the treatment of advanced lung cancer patients. In addition, a subgroup analysis of the clinical characteristics of the enrolled patients was performed to explore possible influencing factors. Methods: This study reviewed the medical records of eligible patients who received ICIs at our institution. The clinicopathological features and clinical outcomes were compared. Also, the use of OA was collected. Patient survival, the incidence of immune-related adverse events (irAEs), and other baseline variables were examined in both cohorts according to whether OA was used. Results: A total of 132 patients were included in the study. Of them, 39 (29.5%) were in the OA-treated group. No significant differences in baseline characteristics were observed between the OA-treated and untreated groups. The combined application of OA treatment significantly shortened progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.002). However, both groups experienced similar incidences and gradations of irAEs. According to multivariate analysis, OA treatment resulted in significantly worse PFS (HR = 4.994, 95% CI 3.217–7.753, P < 0.001) and OS (HR = 3.618, 95% CI 2.030–6.240, P < 0.001). Conclusions: Clinical outcomes of ICIs were significantly diminished in a cohort of Chinese patients with advanced lung cancer receiving OA therapy.

Palbociclib is the first CDK4/6 inhibitor approved by FDA and has been studied in many types of cancer. However, some studies showed that it could induce epithelial-mesenchymal transition (EMT) of cancer cells. To test the effect of palbociclib on non-small-cell lung cancer (NSCLC) cells, we treated NSCLC cells with different concentrations of palbociclib and detected its effects via MTT, migration and invasion assays, and apoptosis test. Further RNA sequencing was performed in the cells treated with 2μM palbociclib or control. And Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and protein-protein interaction network (PPI) were analyzed to explore the mechanism of palbociclib. The results showed that palbociclib significantly inhibited the growth of NSCLC cells and promoted apoptosis of cells, however, enhanced the migration and invasion abilities of cancer cells. RNA sequencing showed that cell cycle, inflammation-/immunity-related signaling, cytokine-cytokine receptor interaction, and cell senescence pathways were involved in the process, and CCL5 was one of the significantly differential genes affected by palbociclib. Further experiments showed that blocking CCL5-related pathways could reverse the malignant phenotype induced by palbociclib. Our results revealed that palbociclib-induced invasion and migration might be due to senescence-associated secretory phenotype (SASP) rather than EMT and suggested that SASP could act as a potential target to potentiate the antitumor effects of palbociclib in cancer treatment.

A gadolinium ions-chelated natural anthocyanin nanoprobe for photoacoustic/magnetic resonance dual-modal imaging-guided tumor photothermal therapy.