Bone Marrow Mesenchymal Stem Cells Derived Discoidin Domain-Containing Receptor 2 (DDR2) as a Communication Mediator to Strengthen the Invasiveness and Metastasis of Papillary Thyroid Carcinoma

Our current study plans to dissect the impacts and its underlying mechanisms of bone marrow mesenchymal stem cells (BMSCs) on the invasive and metastatic features of PTC. Clinical specimens from distantly metastatic PTC were collected to measure DRR2 level. After being identified via tri-lineage differentiation and flow cytometry, BMSCs were co-cultured with PTC cells followed by analysis of cell proliferation and migration by CCK-8 and Transwell assays, expression of DDR2 and EMT-associated proteins by Western blot. Eventually, shDDR2-transfected BMSCs were infused with PTC cells into the abdominal cavity of mice to establish a mouse model assess their effect on tumor growth and distant metastasis. DDR2 was upregulated in BMSCs and malignant cells located in the metastatic sites. Co-culture with BMSCs enhanced DRR2 expression in PTC cells, which was simultaneously accompanied by the escalated mesenchymalization process. In vivo experiments exhibited that co-injection with BMSCs facilitated disease progression and distant metastasis of malignancies. Instead, DDR2 knockdown significantly impeded BMSCs-triggered migrative and proliferative behaviors of malignant cells. In conclusion, DDR2 derived from BMSCs can function as a communication mediator to strengthen the invasiveness and metastasis of PTC.

A comprehensive framework for analysis of microRNA sequencing data in metastatic colorectal cancer

ABSTRACT Although microRNAs (miRNAs) contribute to all hallmarks of cancer, miRNA dysregulation in metastasis remains poorly understood. The aim of this work was to reliably identify miRNAs associated with metastatic progression of colorectal cancer (CRC) using novel and previously published next-generation sequencing (NGS) datasets generated from 268 samples of primary (pCRC) and metastatic CRC (mCRC; liver, lung and peritoneal metastases) and tumor adjacent tissues. Differential expression analysis was performed using a meticulous bioinformatics pipeline, including only bona fide miRNAs, and utilizing miRNA-tailored quality control and processing. Five miRNAs were identified as up-regulated at multiple metastatic sites Mir-210_3p, Mir-191_5p, Mir-8-P1b_3p [mir-141–3p], Mir-1307_5p and Mir-155_5p. Several have previously been implicated in metastasis through involvement in epithelial-to-mesenchymal transition and hypoxia, while other identified miRNAs represent novel findings. The use of a publicly available pipeline facilitates reproducibility and allows new datasets to be added as they become available. The set of miRNAs identified here provides a reliable starting-point for further research into the role of miRNAs in metastatic progression.

Anti-PD-1 combined sorafenib versus anti-PD-1 alone in the treatment of advanced hepatocellular cell carcinoma: a propensity score-matching study

Background Vascular endothelial growth factor (VEGF) plays a role in the tumor microenvironment. Sorafenib, which inhibits the VEGF pathway, has an immune-modulation function but lacks substantial clinical data. This study aims to explore the efficacy of anti-PD-1 combined sorafenib in advanced hepatocellular carcinoma (HCC). Methods HCC patients who underwent anti-PD-1 treatment at Taipei Veterans General Hospital (Taipei, Taiwan) between January 2016 and February 2019 were reviewed. The efficacy was compared between groups after propensity-score matching. Results There were 173 HCC patients receiving anti-PD-1. After excluding unsuitable cases, 140 patients were analyzed, of which 58 received combination therapy and 82 received anti-PD-1 alone. The combination therapy had a trend of higher CR rate (8.6% vs. 4.9%, ns.), ORR (22.4% vs. 19.5%, ns.) and significantly higher DCR (69.0% vs. 37.8%, p < 0.05) comparing to anti-PD-1 alone. After matching, combination group achieved longer progression-free survival (3.87 vs. 2.43 months, p < 0.05) and overall survival (not reached vs. 7.17 months, p < 0.05) than anti-PD-1 alone, without higher grade 3/4 AE (10.3% vs. 7.1%, p = 0.73). The tumor response varied among different metastatic sites, with high responses in adrenal glands, peritoneum and lungs. The more AFP declined (> 10, > 50 and > 66%), the higher the ORR (70, 80 and 92%) and CR rates (30, 35 and 58%) were achieved at day 28. Conclusions This is the first study to demonstrate the combination of anti-PD-1 and sorafenib had better efficacy and survival benefit. A prospective randomized study is needed to confirm this finding.

Fusobacterium nucleatum and Bacteroides fragilis detection in colorectal tumours: Optimal target site and correlation with total bacterial load

Background Mucosal infiltration by certain bacterial species may contribute to the development and progression of colorectal cancer (CRC). There is considerable variation in reported detection rates in human CRC samples and the extent to which bacterial infiltration varies across regions of the primary tumour is unknown. This study aimed to determine if there is an optimal site for bacterial detection within CRC tumours. Methods Presence of target bacterial species was assessed by quantitative real-time PCR (qPCR) in 42 human CRC tumours. Abundance in primary tumour regions, normal epithelium and at metastatic sites was investigated in an expanded cohort of 51 patients. Species presence/absence was confirmed by diversity profiling in five patients. Correlation with total bacterial load and clinicopathological features was assessed. Results Fusobacterium nucleatum and Bacteroides fragilis were detected in tumours from 43% and 24% of patients, respectively (17% positive for both species). The optimal detection site was the tumour luminal surface (TLS). Patients testing positive at the TLS frequently tested negative at other sites, including central tumour and invasive margin. F. nucleatum was detected at a higher frequency in tumour versus normal epithelium (p < 0.01) and was associated with more advanced disease (p = 0.01). Detection of both species correlated with total bacterial load. However, corroboration of qPCR results via diversity profiling suggests detection of these species may indicate a specific microbial signature. Conclusions This study supports a role for F. nucleatum in CRC development. Presence of F. nucleatum and B. fragilis varies across primary tumour regions, with the TLS representing the optimal site for bacterial detection.

Localisation Buccale Secondaire D’un Carcinome Renal

Renal cell carcinomas are tumors known for their metastatic potential. The lungs, the lymph nodes, the lungs, the spleen, the adrenal gland and the cervix remain the metastatic sites of predisposition. The symptoms of metastatic lesion may be due to the initial manifestation of renal malignancy. We report in this work a buccal localization of metastases from renal cell carcinoma to clear cells in a patient aged 65 years or less in our department of otolaryngology and cervical-facial surgery.

Patterns of Distant Metastases in Patients With Triple-Negative Breast Cancer –– A Population-Based Study

Background Currently, the prognosis of triple-negative breast cancer (TNBC) patients remained poor mainly due to resistance, recurrence, metastasis and severe side effects. The study provided systematic insights into the patterns of TNBC distant metastases (DM), as well as investigating the related elements for the prognosis prediction of TNBC patients on the basis of on large sample. Methods We screened eligible patients with triple-negative breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Besides, we analyzed differences in baseline characteristics among patients with diverse modes of metastasis. Meanwhile, we calculated proportional mortality ratio (PMR) and the expression of proportional trends in different patients. Subsequently, Kaplan-Meier (KM) analysis was employed to investigate the survival outcomes. Finally, the predictive and prognostic factors of DM were identified. Results In this study, we included 24,822 TNBC patients, including 1,026 DM patients and 23,796 non-DM patients. At the time of initial diagnosis, 4.1% of patients had DM, and 36.9% had multiple metastases. According to the study, the most common sites of metastasis in DM patients were bone (251 cases) and lung (244 cases), while the least common organ of metastasis was brain (37 cases). Age, tumor grade, T, N and marital status were deemed as risk elements of DM. T stage, insurance status, marital status, surgery treatment, chemotherapy, number of metastatic sites and metastatic sites also effect the diagnosis of DM significantly. Conclusion Our study showed that the most common site of metastasis in TNBC patients with DM was bone and the least common site was brain. Different modes of metastasis have different survival and prognostic characteristics. Thus, our research may have important implications for the clinical practice of TNBC patients in the future.

Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study

Solitary fibrous tumors (SFT) are mesenchymal neoplasms with a favorable prognosis usually originating from the visceral pleura. Rarely, they may occur at various extrapleural sites and show malignant behavior coupled with dedifferentiation. NAB2-STAT6 fusion gene and STAT6 nuclear expression are biomarkers for diagnosis of SFT in addition to CD34, Bcl-2, and CD99. Furthermore, several reports have shown specific NAB2-STAT6 fusion variants and loss of STAT6 protein expression are associated with malignancy. We report a rare case of retroperitoneal SFT which rapidly progressed to death within 35 days after admission. Autopsy found a primary tumor containing both benign and malignant histologies, with multiple metastatic sites similar to the malignant, dedifferentiated tumor. STAT6 was detected in the primary differentiated tumor but not in the primary dedifferentiated tumor or lung/liver metastases. However, the NAB2-STAT6 fusion gene (NAB2ex6/STAT6ex16 variant) was detected in the primary tumor and lung/liver metastases. Intriguingly, fusion gene expression at the transcriptional level was downregulated in the dedifferentiated tumors compared to the differentiated tumor. We further performed target DNA sequencing and found gene mutations in TP53, FLT3, and AR in the dedifferentiated tumors, with TP53 mutations especially found among them. We demonstrate that downregulation of NAB2-STAT6 fusion gene at the transcriptional level is associated with malignant SFT for the first time. Moreover, the present study supports the idea that TP53 mutations promote malignancy in SFTs.