Expression and bioinformatics analysis of RPL38 protein and mRNA in gastric cancer.

We aimed to clarify the expression of RPL38 in gastric cancer, explore the relationship between the expression level of RPL38 and the clinicopathological parameters and prognosis of gastric cancer patients, and explore whether RPL38 has the potential to be used as a therapeutic target for gastric cancer and a biomarker for assessing prognosis. The mRNA and protein expression of RPL38 in gastric cancer tissues and normal tissues were compared by TIMER, Kaplan-Meier plotter, CCLE and UALCAN databases, respectively. Next, the relationship between the expression level of RPL38 in gastric cancer tissues and clinicopathological features was analysed using the UALCAN database. The Kaplan-Meier plotter database was then used to predict the prognostic value of RPL38 in gastric cancer patients, and overall survival curves were plotted based on the follow-up information of clinical specimens. The relationship between RPL38 expression and the level of immune infiltration in gastric cancer was explored using the TIMER database. Finally, co-expression analysis as well as enrichment analysis of RPL38 was performed using LinkedOmics database and GSEA, respectively. Through comprehensive bioinformatics analysis and immunohistochemistry experiments, we comprehensively concluded that RPL38 was highly expressed in gastric cancer. Univariate analysis showed that TNM stage (P=0.008), radiotherapy (P=0.02), and RPL38 expression level (P=0.0006) were associated with prognosis. Multifactorial analysis showed that RPL38 expression level (P=0.019), TNM stage (P=0.015) and radiotherapy (P=0.039) were independent risk factors affecting the prognosis of gastric cancer. Gastric cancer patients with high expression of RPL38 had poorer OS. In addition, RPL38 was associated with immune infiltration in gastric cancer. RPL38 is highly expressed in gastric cancer tissues, and RPL38 protein plays an important role in the development of gastric cancer, which is one of the important factors in assessing the prognosis of gastric cancer patients.

The emerging landscape of exosomal CircRNAs in solid cancers and hematological malignancies.

Circular RNAs (circRNAs) are a type of recently discovered noncoding RNA. They exert their biological functions by competitively binding to microRNAs (miRNAs) as miRNA sponges, promoting gene transcription and participating in the regulation of selective splicing, interacting with proteins and being translated into proteins. Exosomes are derived from intracavitary vesicles (ILVs), which are formed by the inward budding of multivesicular bodies (MVBs), and exosome release plays a pivotal role in intercellular communication. Accumulating evidence indicates that circRNAs in exosomes are associated with solid tumor invasion and metastasis. Additionally, emerging studies in the last 1 ~ 2 years have revealed that exosomal circRNA also have effect on hematological malignancies. In this review, we outline the properties and biological functions of circRNAs and exosomes. In particular, we summarize in detail the mechanism and roles of exosomal circRNAs and highlight their application as novel biomarkers in malignant tumors.

Effective response to crizotinib of concurrent KIF5B-MET and MET-CDR2-rearranged non-small cell lung cancer: A case report.

BACKGROUND: Due to the rarity of mesenchymal-epithelial transition factor (MET) fusions, the clinical efficacy of crizotinib has only been described in a few patients with MET fusions involving various fusion partners. Herein, we report the clinical response to crizotinib of a patient with advanced poorly differentiated non-small cell carcinoma (NSCLC) having concurrent MET fusions. CASE SUMMARY: A 46-year-old woman was diagnosed with poorly differentiated NSCLC (T4N3M1). With no classic driver mutations, she was treated with two cycles of gemcitabine and cisplatin without clinical benefit. Targeted sequencing revealed the detection of two concurrent MET fusions, KIF5B-MET and novel MET-CDR2. Crizotinib was initiated at a dose of 250 mg twice daily. Within 4 wk of crizotinib therapy, repeat computed chromatography revealed a dramatic reduction in primary and metastatic lesions, assessed as partial response. She continued to benefit from crizotinib for 3 mo until disease progression and died within 1 mo despite receiving nivolumab therapy. CONCLUSION: Crizotinib sensitivity was observed in an advanced poorly differentiated NSCLC patient with concurrent MET fusions KIF5B-MET and MET-CDR2. Crizotinib can serve as a therapeutic option for patients with MET fusions. In addition, our case also highlights the importance of comprehensive genomic profiling particularly in patients with no classic driver mutation for guiding alternative therapeutic decisions.

Flavonoids from Scutellaria barbata D. Don exert antitumor activity in colorectal cancer through inhibited autophagy and promoted apoptosis via ATF4/sestrin2 pathway.

PURPOSE: Scutellaria barbata D. Don (SB), mainly containing flavonoids, has been frequently used for cancer treatment. However, little research has investigated the antitumor activity of flavonoids from SB (FSB). The current study aimed to assess the antitumor effect of TFSB and elucidate the probable underlying mechanism in vivo and in vitro. STUDY DESIGN: FSB was prepared, and its chemical composition was characterized by HPLC-MS. Colorectal HCT116 cells were treated with various concentration of FSB. The viability, proliferation, apoptosis, migration, and autophagy of HCT116 cells were studied, as were further confirmed in tumor xenografts. METHODS: Cell viability and proliferation were respectively examined by MTT and EdU staining. ROS was determined with DCFH-DA, and cell apoptosis was detected using flow cytometry. Transwell and wound-healing assays were performed to evaluate cell migration. Immunofluorescence was employed to evaluate sestrin2 and ATF4 level. The protein expressions of p-AMPK, p-ULK1, p-mTOR, 4E-BP1, LC3-I/II, cleaved-caspase-3, Bax, and bcl-2 were investigated by western blot. ATF4 was overexpressed in experiments to explore the role of ATF4/sestrin2 pathway in FSB-mediated efficacy. RESULTS: FSB clearly reduced the cell viability, promoted ROS generation, and induced apoptosis in HCT116 cells by down-regulated Bcl-2, and increased cleaved-caspase-3 and Bax. Furthermore, FSB significantly inhibited migration of colorectal cells in a dose-dependent manner. Further mechanistic study indicated that FSB upregulated p-mTOR protein level, and reduced p-AMPK, p-ULK1, p-mTOR, p-4E-BP1 and LC3-I/II expression, which were major autophagy-related genes. In addition, FSB could cause downregulation of endogenous mTOR inhibitor sestrin2 and ATF4 expression. Transient overexpression of ATF4 resulted in mTOR and sestrin2 inhibition, and significantly compromised the effects of FSB on apoptosis and autophagy in HCT116 cells. CONCLUSION: Our results reveal, for the first time, that FSB exerts antitumor activity through autophagy inhibition and apoptosis induction via ATF4/sestrin2 pathway in colorectal cancer cells. Scutellaria barbata D. Don may have great potential in the application for the prevention and treatment of human colorectal cancer.

Prognostic significance of clinical characteristics and 18Fluorodeoxyglucose-positron emission tomography/computed tomography quantitative parameters in patients with primary mediastinal B-cell lymphoma.

OBJECTIVE: Primary mediastinal B-cell lymphoma (PMBCL) lacks standard treatment regimens. This study aimed to identify the disease's clinical features and prognostic factors. METHODS: This retrospective study included 56 patients with PMBCL. Patient demographic details and clinicopathological characteristics were summarized, and their effects on progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: The median patient age was 29 years (range, 14-56). Twenty-two patients received DA-EPOCH-R (dose-adjusted etoposide, vincristine, and doxorubicin for 96 hours with bolus doses of cyclophosphamide and oral prednisone, as well as rituximab), and 34 patients received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Clinical/laboratory parameters, overall response rates, and 5-year PFS and OS rates did not differ between the treatment groups. Kaplan-Meier analysis indicated that late-stage disease and a higher International Prognostic Index (IPI) were associated with shorter PFS and OS. Furthermore, patients with B symptoms and first-line treatment non-responders exhibited worse OS. 18Fluorodeoxyglucose-positron emission tomography/computed tomography quantitative parameters, such as higher metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were corrected with shorter PFS. CONCLUSIONS: This study revealed that stage IV disease, higher IPI, and B symptoms were poor prognostic factors in patients with PMBCL. Significantly, higher MTV and TLG portended worse PFS.

Novel Insights Into MALAT1 Function as a MicroRNA Sponge in NSCLC.

The long non-coding RNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was initially found to be overexpressed in early non-small cell lung cancer (NSCLC). Accumulating studies have shown that MALAT1 is overexpressed in the tissue or serum of NSCLC and plays a key role in its occurrence and development. In addition, the expression level of MALAT1 is significantly related to the tumor size, stage, metastasis, and distant invasion of NSCLC. Therefore, MALAT1 could be used as a biomarker for the early diagnosis, severity assessment, or prognosis evaluation of NSCLC patients. This review describes the basic properties and biological functions of MALAT1, focuses on the specific molecular mechanism of MALAT1 as a microRNA sponge in the occurrence and development of NSCLC in recent years, and emphasizes the application and potential prospect of MALAT1 in molecular biological markers and targeted therapy of NSCLC.

Epigenetic abnormalities of classical Hodgkin lymphoma and its effect on immune escape.

Classical Hodgkin lymphoma (cHL) is a particular kind of malignant tumour that originates from the B cells. The malignant phenotype of cHL is, at least in part, maintained by epigenetic aberrations, which primarily consist of abnormal histone methylation and acetylation. Progress has been made in clinical trials concerning the histone deacetylases inhibitors (HDACis) in cHL. Also, some demethylation regimens could serve the purpose of preventing and treating tumours. Programmed death-ligand receptor 1 (PD-L1, CD274) inhibitors or apoptosis receptor 1 (PD-1, CD279) inhibitors are used in treating patients with relapsed cHL in recent years. Academic researches indicated that PD-1/PD-L1 inhibitors, including nivolumab and pembrolizumab, demonstrate remarkable activity in relapsed cHL. In addition, in recent years, a close association between epigenetic aberrations and immune escape has been explored in cHL. DNA methyltransferase (DNMT) inhibitors, HDACis, and immune checkpoint blockade exhibit synergistic effects. Thus, this review aims to provide an overview on the epigenetic abnormalities of cHL and its effect on immune escape, in order to explore the optimal combination approach to treat the disease. SIGNIFICANCE OF THE STUDY: Cancer Statistics 2018 reported that more than 8000 new cases of Hodgkin lymphoma were diagnosed. In recent years, PD-1/PD-L1 inhibitors for cHL have been utilized, and the therapeutic strategies of HDACis combined with PD-1/PD-L1 inhibitors have been raised. It is critical for improving the efficacy and decreasing the toxicity in treating the patients with cHL.

Resveratrol inhibits glioma cell growth via targeting LRIG1.

PURPOSE: To investigate the effect of resveratrol on the expression of leucine repeat immunoglobulin-like protein 1 (LRIG1) in glioma cell line U251 and the relationship between LRIG1 and U251 cell proliferation and apoptosis, so as to clarify other molecular mechanisms of resveratrol and look for possible new targets for the treatment of this condition. METHODS: U251 cells were treated with 100µM resveratrol for 48 hrs. Reverse transcription- polymerase chain reaction (RT-PCR) and Western blotting were used to detect the LRIG1 level in glioma cell line U251 and the expressions of related factors after resveratrol treatment. The loss-of-function assay was performed via transfection of LRIG1 small interference and the proliferation and apoptosis of U251 cells in each group were detected via MTT assay and flow cytometry. RESULTS: The mRNA and protein expression levels of LRIG1 in U251 cells were up-regulated after resveratrol treatment, accompanied with decreased Epidermal Growth Factor Receptor (EGFR). MTT assay showed that the cell proliferation rate was decreased after resveratrol treatment, and flow cytometry showed that cell apoptosis was increased. The loss-of-function assay via transfection of LRIG1 small interference showed that resveratrol could reverse the increased cell proliferation and decreased apoptosis induced by LRIG1 small interference. CONCLUSIONS: Resveratrol can inhibit the growth and proliferation of glioma and promote its apoptosis through upregulating the LRIG1 gene expression, which plays the effect of antiglioma growth, revealing that LRIG1 is a new biological target of resveratrol in antiglioma cell proliferation and growth.