Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study.

BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

A nomogram model for predicting distant metastasis of newly diagnosed colorectal cancer based on clinical features.

Objective: Colorectal cancer is one of the most common primary malignancies and the third most common cause of cancer death in both men and women in the United States. Among people diagnosed with initial colorectal cancer, 22% had metastatic colorectal cancer, while the 5-year survival rate was less than 20%. The purpose of this study is to develop a nomogram for predicting distant metastasis in newly diagnosed colorectal cancer patients and to identify high-risk groups. Methods: We retrospectively reviewed the data of patients who were diagnosed with colorectal cancer at Zhong nan Hospital of Wuhan University and People's Hospital of Gansu Province between January 2016 and December 2021. Risk predictors for distant metastasis from colorectal patients were determined by the univariate and multivariate logistic regression analyses. Nomograms were developed to predict the probabilities of distant metastatic sites of colorectal cancer patients and evaluated by calibration curves, receiver operating characteristic curves, and decision curve analysis (DCA). Results: A total of 327 cases were included in this study: 224 colorectal cancer patients from Zhong nan Hospital of Wuhan University were incorporated into the training set, and 103 colorectal cancer patients from Gansu Provincial People's Hospital were incorporated into the testing set. By univariate logistic regression analysis, platelet (PLT) level (p = 0.009), carcinoembryonic antigen (CEA) level (p = 0.032), histological grade (p < 0.001), colorectal cancer tumor markers (p < 0.001), N stage (p < 0.001), and tumor site (p = 0.005) were associated with distant metastasis in colorectal cancer patients. Multivariate logistic regression analysis showed that N stage (p < 0.001), histological grade (p = 0.026), and colorectal cancer markers (p < 0.001) were independent predictors of distant metastasis in patients initially diagnosed with colorectal cancer. The above six risk factors were used to predict distant metastasis of newly diagnosed colorectal cancer. The C-indexes for the prediction of the nomogram were 0.902 (95% confidence interval (CI), 0.857-0.948). Conclusion: The nomogram showed excellent accuracy in predicting distant metastatic sites, and clinical utility may facilitate clinical decision-making.

Corrigendum: An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness.

[This corrects the article DOI: 10.3389/fcell.2020.00287.].

Erratum: The WW domains dictate isoform-specific regulation of YAP1 stability and pancreatic cancer cell malignancy: Erratum.

[This corrects the article DOI: 10.7150/thno.42795.].

An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness.

Cancer stemness is associated with high malignancy and low differentiation, as well as therapeutic resistance of tumors including pancreatic ductal adenocarcinoma (PDAC). Fibroblast growth factors (FGFs) exert pleiotropic effects on a variety of cellular processes and functions including embryonic stem cell pluripotency and cancer cell stemness via the activation of four tyrosine kinase FGF receptors (FGFRs). FGF ligands have been a major component of the cocktail of growth factors contained in the cancer stemness-inducing (CSI) and organoid culture medium. Although FGF/FGFR signaling has been hypothesized to maintain cancer stemness, its function in this process is still unclear. We report that inhibition of FGF/FGFR signaling impairs sphere-forming ability of PDAC in vitro, and knocking down FGFR1 and FGFR2 decreased their tumorigenesis abilities in vivo. Mechanistically, we demonstrated that SOX2 is down-regulated upon loss of FGFR signaling. The overexpression of SOX2 in SOX2-negative cells, which normally do not display stemness capabilities, is sufficient to induce spheroid formation. Additionally, we found that AKT phosphorylation was reduced upon FGFR signaling inhibition. The inhibition of AKT using specific pharmacological inhibitors in the context of CSI medium leads to the loss of spheroid formation associated with loss of SOX2 nuclear expression and increased degradation. We demonstrate that an FGFR/AKT/SOX2 axis controls cancer stemness in PDAC and therefore may represent an important therapeutic target in the fight against this very aggressive form of cancer.

The WW domains dictate isoform-specific regulation of YAP1 stability and pancreatic cancer cell malignancy.

YAP1 is a key mediator of the Hippo pathway capable of exerting a profound effect on organ size as well as tumorigenesis. Alternative mRNA splicing of human YAP1 results in at least 8 protein isoforms that differ within the 2nd WW motif and the transcriptional activation domain. Methods: To investigate the isoform-specific differences in their mRNA expression, transcriptional activity and tumor-promoting function, we cloned cDNA encoding all of the eight YAP1 protein isoforms. Then, we examined their mRNA expression, subcellular localization, transcriptional regulation properties, interactions with key regulatory partners, and protein stability in response to changes in cell density, as well as their effects on pancreatic cancer cell malignancy both in vitro and in vivo. Results: Multiple YAP1 mRNA isoforms are expressed in commonly used pancreatic cancer lines as well as human pancreatic cancer PDX lines. Based on the analysis of heterologous reporter and endogenous target genes, all YAP1 isoforms are capable of activating transcription, albeit to a different extent. Importantly, we unveiled a marked discrepancy between the mRNA and protein expression levels of the YAP1-1 and YAP1-2 isoforms. We further discovered that the YAP1-2 isoform, which contains two tandem WW motifs, is less stable at the protein level, particularly at high cell densities. Mechanistically, we found that the presence of the 2nd WW motif in YAP1-2 facilitates the de novo formation of the YAP1-2/AMOT/LATS1 complex and contributes to a stronger binding of YAP1-2 to LATS1 and subsequently increased YAP1-2 ubiquitination and degradation by ß-TRCP. Conclusion: Our data reveals a potent effect of YAP1-1 on pancreatic cancer malignancy in vitro and in vivo and provides novel mechanistic insight into isoform-specific and cell density-dependent regulation of YAP1 stability, as well as its impact on cancer malignancy.