Teriprizumab-induced myocarditis in a patient with cholangiocarcinoma: a case report.

With the extensive use of immune checkpoint inhibitors (ICI) in advanced-stage cancers, immune-related adverse events (irAEs) have been noted in various systems. While most irAEs are reversible and manageable, cardiac toxicities are rare but life-threatening, with high mortality rates. We present a case of a 71-year-old man with cholangiocarcinoma who developed myocarditis related to ICIs 29 days after the first infusion of teriprizumab combined with albumin-bound paclitaxel and gemcitabine. He was initially asymptomatic after admission but with substantial elevations of troponin I and myocardial enzymes. Sixteen hours after admission, he developed palpitations, dizziness, and syncope. Electrocardiography confirmed third-degree atrioventricular block and frequent ventricular premature contractions for which he received high-dose corticosteroids and a permanent pacemaker. The patient survived and permanently discontinued immunotherapy. Early identification and intervention are the keys to improving the prognosis of immune myocarditis.

Immunotherapy Mechanism of Esophageal Squamous Cell Carcinoma with the Effect of STK11/AMPK Signaling Pathway.

This study was aimed at exploring the mechanism of serine threonine protein kinase 11 (STK11)/Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway after immunotherapy for esophageal squamous cell carcinoma (ESCC), providing basic information for the clinical treatment of ESCC. In this study, tissue specimens from 100 patients with ESCC who underwent surgical treatment in Taizhou People's Hospital (group A) and 20 patients with recurrent or metastatic ESCC who received second-line immunotherapy (group B) were collected. The real-time fluorescent quantitative polymerase chain reaction (PCR) (RT-qPCR) technology was used to detect the expression levels of STK11, interferon-γ (IFN-γ), interleukin 6 (IL-6), and vascular endothelial growth factor (VEGF) in the tissues. The immunohistochemical staining was used to detect the positive expression levels (PELs) of STK11 and AMPKα in the tissues, and immunofluorescence staining was used to detect the PELs Teff cells (CD3 and CD8), Treg cells (CD4 and FOXP3), and neutrophils (CD68 and CD163). RT-qPCR results showed that the expression levels of STK11 and IFN-γ in group A were obviously lower, and those of IL-6 and VEGF were much higher in contrast to group B (P < 0.05). The results of immunohistochemical staining showed that the number of STK11- and AMPKα-positive staining cells in group A was dramatically less than that in group B (P <0.05). The results of immunofluorescence staining revealed that the number of positive staining cells for Teff cells, Treg cells, and neutrophils in group A was also less dramatically than that in group B (P <0.05). In summary, immunotherapy can play a therapeutic effect on ESCC by regulating STK11/AMPK pathway and immune cell infiltration.

Breast metastases in advanced rectal cancer: a case report.

Breast metastasis from solid tumors rarely occurs, although primary breast cancer is one of the most common malignancies in women worldwide. Rectal cancer metastasis is rarely reported. We report a case of a 49-year-old Chinese woman with advanced rectal cancer, who presented with mass in her left breast and several irregular dusky-red nodular knurls in the skin around the left nipple. Based on percutaneous echo-guided biopsy of the breast lesion, a poorly differentiated adenocarcinoma was consistent with rectal cancer metastasis histologically and immunohistochemically. This should be considered in any patient with history of cancer and confirmed histologically and immunohistochemically.

Long Non-Coding RNA SPRY4-IT1 Reverses Cisplatin Resistance by Downregulating MPZL-1 via Suppressing EMT in NSCLC.

PURPOSE: Long non-coding RNA (lncRNA) SPRY4 intronic transcript 1 (SPRY4-IT1) is reported to play important roles in the occurrence and development of many tumors. However, the possible role of SPRY4-IT1 in cisplatin (DDP) resistance of non-small-cell lung cancer (NSCLC) remains unclear. The aim of this study is to investigate the functions and molecular mechanisms underlying SPRY4-IT1 of cisplatin resistance in NSCLC. METHODS: Expression of SPRY4-IT1 was analyzed in A549 and cisplatin-resistant A549/DDP cell lines by quantitative real-time polymerase chain reaction (RT-qPCR). Overexpression techniques were applied to investigate the biological functions of SPRY4-IT1 in cisplatin-resistant A549/DDP cells. The effects of SPRY4-IT1 on proliferation and apoptosis were evaluated using cell counting kit-8 (CCK8) assays, colony formation assay and flow-cytometric analysis. The expressions of epithelial-mesenchymal transition (EMT)-associated proteins, including E-cadherin and Vimentin, were detected by Western blot. Microarray analysis was performed to identify the putative targets of SPRY4-IT1, which were further verified by Western blotting and RT-qPCR. A549/DDP cells transfected with pCDNA-SPRY4-IT1 were injected into nude mice in order to verify the effect of SPRY4-IT1 on cisplatin resistance in vivo. RESULTS: The present study demonstrated that SPRY4-IT1 expression was decreased in A549/DDP cells compared with parental A549 cells. Upregulation of SPRY4-IT1 suppressed cell proliferation and caused apoptosis of A549/DDP cells both in vitro and in vivo. MPZL-1 was negatively regulated by SPRY4-IT1. Furthermore, upregulation of SPRY4-IT1 and downregulation of MPZL-1 could suppress epithelial-mesenchymal transition (EMT), which was characterized by increased E-cadherin expression and decreased Vimentin expression. CONCLUSION: Upregulation of SPRY4-IT1 reversed the cisplatin-resistant phenotype of NSCLC partially by downregulating MPZL-1 via inhibiting EMT process.

Long noncoding RNA actin filament-associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine-specific demethylase 1 and repressing HMG box-containing protein 1 in non-small-cell lung cancer.

The number of documented long noncoding RNAs (lncRNAs) has dramatically increased, and their biological functions and underlying mechanisms in pathological processes, especially cancer, remain to be elucidated. Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) is a 6810-nt lncRNA located on chromosome 4p16.1 that was first reported to be upregulated in esophageal adenocarcinoma tissues and cell lines. Here we reported that AFAP1-AS1, recruiting and binding to lysine-specific demethylase 1 (LSD1), was generally overexpressed in human non-small-cell lung cancer (NSCLC) tissues using quantitative real-time PCR. Higher AFAP1-AS1 expression was significantly correlated with larger tumor size (P = .008), lymph node metastasis (P = .025), higher TNM stage (P = .024), and worse overall survival in NSCLC patients. In vitro experiments revealed that AFAP1-AS1 downregulation inhibited cell migration and induced apoptosis; AFAP1-AS1 knockdown also hindered tumorigenesis in vivo. Moreover, mechanistic investigations including RNA immunoprecipitation and ChIP assays validated that AFAP1-AS1 repressed HMG box-containing protein 1 (HBP1) expression by recruiting LSD1 to the HBP1 promoter regions in PC-9 and H1975 cells. Furthermore, HBP1 functions as a tumor suppressor, and its ectopic expression hindered cell proliferation. Rescue assays determined that the oncogenic effect of AFAP1-AS1 is partially dependent on the epigenetic silencing of HBP1. In conclusion, our results indicate that AFAP1-AS1 is carcinogenic and that the AFAP1-AS1/LSD1/HBP1 axis could constitute a new therapeutic direction for NSCLC.

Effect of Annexin A1 gene on the proliferation and invasion of esophageal squamous cell carcinoma cells and its regulatory mechanisms.

The aim of this study was to examine the effect of Annexin A1 (ANXA1) on the proliferation, migration and invasion of esophageal squamous cell carcinoma (ESCC) cells and its possible mechanisms of action. After constructing the ANXA1 overexpression plasmid, we transfected this plasmid and/or microRNA (miRNA)­196a mimic into ESCC cells (Eca109 cell line). Methyl thiazolyl tetrazolium (MTT) assay and Transwell chamber assay were performed to determine cell proliferation, migration and invasion, respectively. Western blot analysis was used to examine the protein expression levels of ANXA1, Snail and E-cadherin. RT-PCR was used to detect the expression of miRNA-196a. Our results revealed that ANXA1 expression was upregulated in the cells transfected with the ANXA1 overexpression plasmid, and cell proliferation, migration and invasion were significantly increased (p=0.004, p<0.001 and p=0.011, respectively). In the cells transfected with the miRNA­196a mimic, miRNA­196a expression was significantly upregulated (p<0.001). However, miRNA-196a expression was downregulated in the cells transfected with the ANXA1 overexpression plasmid. In addition, in the cells transfected with the miRNA­196a mimic, cell proliferation, migration and invasion were significantly decreased (p=0.027, p=0.009 and p=0.021, respectively). In the cells transfected with the ANXA1 overexpression plasmid, the expression of Snail was upregulated and that of E-cadherin was downregulated. However, the opposite was observed in the cells transfected with the miRNA­196a mimic. Our findings thus demonstrate that ANXA1 promotes the proliferation of Eca109 cells, and increases the expression of Snail, whereas it inhibits that of E-cadherin, thus enhancing the migration and invasion of ESCC cells. miRNA-196a negatively regulates the expression of ANXA1, thereby inhibiting the proliferation, invasion and metastasis of ESCC cells.

Two-year clinical evaluation of composite resins in non-carious cervical lesions.

OBJECTIVE: The purpose of this double-blind, randomised trial was to compare the clinical performance of a hybrid composite (Clearfil AP-X, Kuraray, Tokyo) and a nanocomposite (Filtek Z350, 3M ESPE, St. Paul, MN) over a period of 2 years in non-carious class V lesions using a modified US Public Health Service (USPHS) system. METHODS: Forty-six patients with at least one pair of equivalent non-carious cervical lesions under occlusion and a mean age of 44.1 years (range 27-66 years; median 45 years) were enrolled in this study. A total of 116 restorations (58 with each material) were placed according to manufacturer's instructions by two calibrated operators. The restorations were evaluated at baseline and at 6, 12 and 24 months after placement using the USPHS criteria for retention, colour match, marginal discolouration, marginal adaptation, anatomic form, surface texture and secondary caries. Statistical analysis was conducted using the Cochran and the McNemar tests at a significance level of 5% (P < 0.05). RESULTS: No surface texture changes or secondary caries were detected in association with any restorations. The retention rates for Clearfil AP-X (100%) and for Filtek Z350 (91.38%) did not differ significantly (P > 0.05). Two Z350 restorations were completely lost after 2 years. No significant differences were observed in the colour match, marginal discolouration, marginal adaptation or anatomic form. CONCLUSIONS: There were no significant differences in the clinical performances between the materials. CLINICAL RELEVANCE: Both restorative materials exhibited acceptable clinical performance in class V non-carious lesions 2 years post-restoration.