Artificial sweetener and respiratory system cancer: A Mendelian randomization analysis.

BACKGROUND & AIMS: The association between artificial sweeteners and various cancers has been investigated, but their relationship with respiratory system cancers remains uncertain. To address this knowledge gap, we conducted a comprehensive Mendelian Randomization (MR) analysis. METHODS: We looked for SNPs associated with artificial sweetener intake and respiratory system cancers from the IEU OpenGWAS project, as well as SNPs related to sweet taste in artificial sweeteners from Hwang et al.'s study. Rigorous quality control procedures were implemented to select instrumental Single Nucleotide Polymorphisms that were closely linked to artificial sweetener intake. To ensure the reliability of our findings, we employed five different analytical methods, with the inverse variance weighting method being the primary approach. Additionally, we thoroughly assessed heterogeneity, pleiotropy, and sensitivity. Finally, we conducted Multivariable Mendelian Randomization (MVMR) to validate our results. RESULTS: Intake of artificial sweetener added to cereal showed a positive association with malignant neoplasm of the lip, oral cavity, and pharynx (OR: 1027.54; 95% CI: 4.8-219994.46; P = 0.011), and the result was also confirmed by the MVMR analysis. In addition, better perceived intensity of aspartame was negatively associated with cancers in these regions (OR: 0.49; 95% CI: 0.28-0.88; P = 0.016). Intake of artificial sweetener added to coffee or tea was not related with respiratory system cancer. CONCLUSIONS: Our research offers evidence that the consumption of artificial sweeteners in cereals could increase the risk of cancers in the lip, oral cavity, and pharynx. Additionally, a greater sensitivity to the taste of aspartame may lower this risk.

Causal Relationships of Chronic Constipation and Irritable Bowel Syndrome with Digestive Tract Cancers: A Mendelian Randomization Study.

BACKGROUND: Chronic constipation and irritable bowel syndrome (IBS) manifest as prevalent gastrointestinal disorders, while digestive tract cancers (DTCs) present formidable challenges to global well-being. However, extant observational studies proffer uncertain insights into potential causal relationships of constipation and IBS with susceptibility to DTCs. METHODS: We executed Mendelian randomization (MR) analysis to establish causal connections between these conditions and seven distinct categories of DTCs, including colorectal carcinoma (CRC), hepatocellular cancer (HCC), esophageal malignancy (ESCA), pancreatic adenocarcinoma (PAAD), biliary tract carcinoma (BTCs), gastric carcinoma (GC), and small intestine neoplasm (SIC). Leveraging instrumental variables (IVs) obtained from GWAS data of the FinnGen database, we employed a range of analytical methodologies, including inverse-variance weighting multiplicative random effects (IVW_MRE), inverse-variance weighting fixed effects (IVW_FE), maximum likelihood (ML), weighted median (WM), MR‒Egger regression, and the MR-PRESSO test. RESULTS: We observed a substantial linkage between genetically predicted constipation and increased vulnerability to PAAD (OR = 2.29, 95% CI: 1.422-3.69, P = 0.001) via the IVW method. Following the removal of outlier SNPs through MR-PRESSO, genetically predicted IBS was affiliated with an increased risk of CRC (OR = 1.17, 95% CI: 1-1.37, P = 0.05). Nonetheless, decisive causal correlations of constipation or IBS with other DTCs remain elusive. CONCLUSION: In summary, genetically predicted constipation was associated with an augmented PAAD risk, and IBS was associated with an increased CRC susceptibility within European cohorts, in agreement with some observational studies. Nevertheless, the causal associations of constipation and IBS with other DTCs remain inconclusive.

DDX24 promotes tumor progression by mediating hexokinase-1 induced glycolysis in gastric cancer.

Metabolic reprogramming allows tumor cells to meet high demand of biogenesis and increased energy for rapid proliferation. Gastric cancer (GC) ranks among the most prevalent malignancies globally. Exploring the underlying mechanisms of glycolytic reprogramming in GC could provide new therapeutic target for GC treatment. Here, we showed that DEAD-box helicase 24 (DDX24) played a critical role in hexokinase-1 (HK1) induced glycolysis. DDX24 expression was significantly elevated in GC tissues and was closely associated with worse survival in GC patients. In addition, DDX24 promoted glucose uptake and lactate production in GC cells. Mechanistically, DDX24 could bind the HK1 mRNA and positively regulated HK1 level at the transcriptional level. Moreover, DDX24 promoted the proliferation, migration, and invasion ability of GC cells by upregulating HK1. Collectively, these results suggested that DDX24 was a critical player in the regulation of glycolytic reprogramming and also implicated DDX24 as a valuable therapeutic target for GC.

Pucotenlimab in patients with advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A multicenter phase 2 study.

We report a multicenter, phase 2 study evaluating the efficacy of pucotenlimab, an anti-PD-1 antibody, in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, and potential biomarkers for response. Overall, 100 patients with previously treated, advanced solid tumors centrally confirmed as dMMR or MSI-H received pucotenlimab at 200 mg every 3 weeks. The most common cancer type is colorectal cancer (n = 71). With a median follow-up of 22.5 months, the objective response rate is 49.0% (95% confidence interval 38.86%-59.20%) as assessed by the independent review committee, while the median progression-free survival and overall survival have not been reached. Grade ≥3 treatment-related adverse events were observed in 18 patients. For the biomarker analysis, responders are enriched in patients with mutations in the KMT2D gene. Pucotenlimab is an effective treatment option for previously treated advanced dMMR/MSI-H solid tumors, and the predictive value of KMT2D mutation warrants further research. This study is registered with ClinicalTrials.gov: NCT03704246.

Peripheral CD4+CD25hiCD127low regulatory T cells are increased in patients with gastrointestinal cancer.

BACKGROUND: Regulatory T cells (Tregs) play an important role in regulation of immune response and immunologic tolerance in cancer. Gastrointestinal cancer is still a leading cause of cancer-related death in the world. This study aimed to detect Tregs in patients with gastrointestinal cancer. METHODS: In this study, 45 gastric cancer patients, 50 colorectal cancer patients and 50 healthy controls were enrolled. Flow cytometry was used to detect CD4+CD25hiCD127low Tregs, CD4+CD25hi, and CD4+ cells in peripheral blood. Cytokine interleukin-10 (IL-10) and transforming growth factor-ß1 (TGF-ß1) in peripheral blood and in the supernatant of Tregs cultures were measured by enzyme linked immunosorbent assay. RESULTS: Compared with healthy controls, the levels of CD4+CD25hiCD127low Tregs and CD4+CD25hi cells increased significantly in patients with gastrointestinal cancer. Patients with gastrointestinal cancer also showed a significantly increased levels of IL-10 and TGF-ß1 in both peripheral blood and CD4+CD25hiCD127low Tregs culture medium. CONCLUSION: The present study firstly demonstrated that gastrointestinal patients have a compromised immune status where the CD4+CD25hiCD127low Tregs, as well as levels of IL-10 and TGF-ß1 are elevated. The data offered new information for understanding the immunological features of gastrointestinal patients, as well as provided new insights into approaches to develop new immunotherapies for patients with gastrointestinal cancer.

Novel Method for Detection of PIK3CA Mutations in Circulating Tumor DNA of Patients with Colorectal Cancer.

The PIK3CA mutation is considered a potential target for treatment of colorectal cancer. We evaluated a PIK3CA mutation assay on plasma cell-free DNA (cfDNA) using a newly developed PCR with restriction digestion integrated and followed by Sanger's sequencing. We analyzed PIK3CA mutation in plasma with our newly developed assays and in matching tumor tissues by routine methods. We detected the PIK3CA gene mutation status by both methods in samples from 40 colorectal cancer patients. Three H1047R mutations of PIK3CA gene were detected in the cfDNA of the 40 patients by restriction digestion PCR. Neither E545K nor H1047R mutations were detected in the cfDNA by routine PCR/sequencing. The PIK3CA H1047R and E545K mutations in cfDNA can be sensitively detected with our newly developed assays. The colorectal cancer has been used as a clinical example in testing our new assays, which indicates that the new assays may have wider applications in detecting mutations in precision oncology. Trial registration: Current Controlled Trials ChiCTR-DDT-12002848, 8 October 2012.

Results of the phase IIa study to evaluate the efficacy and safety of rezivertinib (BPI-7711) for the first-line treatment of locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation from a phase I/IIa study.

BACKGROUND: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This phase IIa study was part of a phase I/IIa study (NCT03386955), aimed to evaluate the efficacy and safety of rezivertinib as the first-line treatment for patients with locally advanced or metastatic/recurrent EGFR mutated non-small cell lung cancer (NSCLC). METHODS: Patients received the first-line treatment of 180 mg rezivertinib orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: From Jun 12, 2019, to Oct 17, 2019, 43 patients were enrolled. At the data cutoff date on Dec 23, 2021, the ORR by BICR was 83.7% (95% CI: 69.3-93.2%). The median DoR was 19.3 (95% CI: 15.8-25.0) months. The median PFS by BICR was 20.7 (95% CI: 13.8-24.8) months and 22.0 (95% CI: 16.8-26.3) months by investigators. Data on OS was immature. Totally, 40 (93.0%) patients had at least one treatment-related adverse event while 4 (9.3%) of them were grade ≥ 3. CONCLUSIONS: Rezivertinib (BPI-7711) showed promising efficacy and a favorable safety profile for the treatment among the locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation in the first-line setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03386955.

[Retracted] MTSS1 inhibits colorectal cancer metastasis by regulating the CXCR4/CXCL12 signaling axis.

Following the publication of the above paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell migration assay data shown in Fig. 1B were strikingly similar to data that had appeared in different form in another article by different authors at a different research institution. Furthermore, a number of overlapping data panels were observed comparing among migration assay data shown in Fig. 1B and C and Fig. 7B, such that these data, which were purported to show the results from differently performed experiments, may have been derived from the same original source(s). Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 47: 65, 2021; DOI: 10.3892/ijmm.2021.4898].

Pain Incidence and Associated Risk Factors among Cancer Patients within 72 Hours after Surgery: A Large Retrospective Analysis.

BACKGROUND: A fundamental principle of pain management is to determine the distribution and causes of pain. However, relevant data among postoperative cancer patients based on a large amount of data remain sparse. OBJECTIVE: We aimed to investigate the incidence of postoperative pain in cancer patients and to explore the associated risk factors. METHODS: We retrospectively collected information on postoperative pain-evaluation records of cancer patients who underwent surgery between 1 January 2014 and 31 December 2019. Descriptive statistics were presented, and multinominal logistic regression analysis was performed to explore the risk factors associated with postoperative pain. RESULTS: Among the 11,383 patients included in the study, the incidence of mild/moderate to severe pain at the 24th hour after surgery was 74.9% and 18.3%, respectively. At the 48th and 72nd hour after surgery, the incidence of mild pain increased slightly, while the incidence of moderate to severe pain continued to decrease. Female patients experienced a higher risk of pain (ORs: 1.37-1.58). Undergoing endoscopic surgery was associated with a higher risk of pain (ORs: 1.40-1.56). Patients with surgical sites located in the respiratory system had a higher risk of pain compared to in the digestive system (ORs: 1.35-2.13), and other patients had a relatively lower risk of pain (ORs: 0.11-0.61). CONCLUSION: The majority of cancer patients experienced varying degrees of postoperative pain but may not receive adequate attention and timely treatment. Female, young age and endoscopic surgery were associated with increased pain risk, and effective identification of these high-risk groups had positive implications for enhanced postoperative pain management.

Diagnostic features and therapeutic strategies for malignant paraganglioma in a patient: A case report.

BACKGROUND: Paragangliomas and extra-adrenal pheochromocytomas are uncommon neuroendocrine tumors with ubiquitous distribution. Malignant paraganglioma is a relatively rare entity. We report the treatment and pathological characteristics of a patient with malignant paraganglioma, and summarize the latest advances in the treatment of malignant paraganglioma based on a literature review. CASE SUMMARY: A 45-year-old Chinese woman presented to the hospital due to pain in the waist (right side) and right buttock, and was diagnosed as malignant paraganglioma after the placement of ureteral stent, implantation of ileus catheter, and transvaginal removal of the vaginal mass. After relief of intestinal obstruction, the patient received intravenous chemotherapy and peritoneal perfusion chemotherapy. Although her pelvic mass disease was stable, she developed multiple liver metastases and bone metastases. Due to the development of spinal cord compression, she underwent orthopedic surgery, followed by radiotherapy, and molecular targeted therapy with apatinib, but with poor disease control. CONCLUSION: Clinical management of paraganglioma is challenging for endocrinologists and oncologists. Prospective studies are required to develop standardized therapeutic strategies for malignant paragangliomas.

A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study).

PURPOSE: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription. RESULTS: The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only. CONCLUSIONS: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.

Inhibition of Musashi-1 enhances chemotherapeutic sensitivity in gastric cancer patient-derived xenografts.

Musashi-1 (MSI1), a neural RNA-binding protein, is considered a gastric and intestinal stem cell marker. Although the function of MSI1 in gastric cancer has attracted increasing interest, it is not known whether MSI1 can be used as a biomarker to monitor gastric cancer development and response to treatment. Here, the role of MSI1 in the chemotherapeutic sensitivity of gastric cancer was investigated. Patients with high MSI1 levels had poor outcomes, implicating the gene in the development and progression of the disease. We overexpressed and silenced MSI1 in the human gastric cancer cell lines MKN45 and HGC27, finding that knockdown reduced proliferation, invasion, and migration, while promoting apoptosis. A patient-derived xenograft gastric cancer model was constructed in which mice received chemical drugs, si-MSI1, or a drug-si-MSI1 combination. It was found that blocking MSI1 expression reduced gastric cancer drug tolerance. The combination treatment with si-MSI1 was superior to 5F-dUMP and cisplatin, either separately or in combination, indicating that including si-MSI1 was better than drug therapy alone. Transcriptome sequencing analysis showed that MSI1 altered cell cycle regulation and growth signal transduction, including that of blood vessel epicardial substance (BVES). These results suggest that MSI1 reduces the tolerance of gastric cancer to chemical drugs through modulation of MSI1/BVES signaling.

Safety, Efficacy, and Pharmacokinetics of Rezivertinib (BPI-7711) in Patients With Advanced NSCLC With EGFR T790M Mutation: A Phase 1 Dose-Escalation and Dose-Expansion Study.

INTRODUCTION: Rezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor selective for EGFR-sensitizing and T790M mutations. This study was designed to evaluate the safety, efficacy, and pharmacokinetics of rezivertinib for patients having advanced NSCLC with EGFR T790M mutation. METHODS: This phase 1 study (NCT03386955) was conducted across 20 sites in the People's Republic of China. Patients received rezivertinib at six oral dose levels (30 mg, 60 mg, 120 mg, 180 mg, 240 mg, 300 mg) once daily until disease progression, unacceptable toxicity, or patient withdrawal. The primary end points were safety for the dose-escalation phase and objective response rate by the blinded independent central review for the total study population. RESULTS: A total of 19 patients in dose-escalation phase using the standard 3 + 3 design principle and 153 patients in dose-expansion phase were enrolled from September 11, 2017, to August 23, 2019. The data cutoff date was on June 15, 2020. No dose-limiting toxicity occurred in the dose-escalation phase. The treatment-related adverse events were observed in 82.0% (141 of 172) of patients, and 17.4% (30 of 172) had grade greater than or equal to 3, among which decreased neutrophil count (2.9%), leukopenia (2.9%), and pneumonia (2.9%) were the most common. The overall blinded independent central review-evaluated objective response rate was 59.3% (102 of 172, 95% confidence interval: 51.6-66.7), and the median progression-free survival was 9.7 (95% confidence interval: 8.3-11.1) months. CONCLUSIONS: Rezivertinib was found to have promising efficacy with a manageable safety profile in patients with EGFR T790M-mutated advanced NSCLC. Further study is warranted.

Long non-coding RNA HAGLROS regulates the proliferation, migration, and apoptosis of esophageal cancer cells via the HAGLROS-miR-206-NOTCH3 axis.

BACKGROUND: Esophageal cancer (EC) is a common malignant tumor of the digestive tract, the treatment of which involves surgery combined with radiotherapy and chemotherapy, as well as other comprehensive types of treatment. The pathogenesis of EC remains unclear, which hinders the development of clinical therapy and the identification of molecular targets for this disease. Long non-coding RNAs (lncRNAs) have been shown to be associated with the malignant biological behavior of EC, but the specific molecular mechanisms underlying the carcinogenesis of EC are not fully understood. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was applied to measure the lncRNA HAGLR opposite strand lncRNA (HAGLROS) levels in EC cell lines and tissues. Cell Counting Kit-8 (CCK-8) detection, scratch test, and Transwell assay were performed to determine the proliferation, migration and invasion of EC cell. The interaction between HAGLROS, microRNA (miR)-206, and notch receptor 3 (NOTCH3) was confirmed by RNA immunoprecipitation and dual luciferase reporter gene assays. RESULTS: HAGLROS is upregulated in esophageal squamous cell carcinoma (ESCC) tissues and predicts poor prognosis. Silent HAGLROS is negatively associated with malignant behavior in EC cells. Low expression of HAGLROS can induce decreased invasive and migratory abilities in EC cells. Downregulated HAGLROS significantly inhibits the proliferation of EC cells and accelerates apoptosis. HAGLROS promotes EC cell tumorigenesis in vivo. HAGLROS participates in the HAGLROS/miR-206/NOTCH3 regulatory axis in EC cells. CONCLUSIONS: HAGLROS may play a role in the progression of EC by modulating the miR-206/NOTCH3 signaling axis, and may be a novel target for the diagnosis and treatment of EC.

Downregulation of LINC00115 inhibits the proliferation and invasion of lung cancer cells in vitro and in vitro.

BACKGROUND: Lung cancer is a common malignant tumor in clinical practice. Its morbidity and mortality rank first among malignant tumors. However, the pathogenesis of lung cancer has not been fully clarified. This study found that LINC00115 is highly expressed in lung cancer tissues, but the role and molecular mechanisms of LINC00115 in the occurrence and progression of lung cancer are still unclear. METHODS: Fluorescence quantitative PCR was used to detect the expression of LINC00115 in lung cancer tissues and para-carcinoma tissues. Cell counting kit-8 (CCK-8), clone formation, and Transwell assays were used to detect the effects of LINC00115 knockdown on the proliferation, clone formation, invasion, and migration of lung cancer cells. Western blot was used to detect the effects of LINC00115 knockdown on the expression of epithelial-mesenchymal transition (EMT)-related molecules. Finally, a xenograft model in nude mice was used to detect the effect of LINC00115 knockdown on the proliferation of lung cancer cells in vivo. RESULTS: Compared with para-carcinoma tissue, LINC00115 was highly expressed in lung cancer tissue. Cell function experiments showed that knockdown of LINC00115 could significantly inhibit the proliferation, invasion, and migration of lung cancer cells. Western blot results showed that knockdown of LINC00115 could significantly inhibit the expression of the EMT-related proteins N-cadherin, vimentin, and fibronectin, and promoted the expression of E-cadherin. In vivo experiments in nude mice showed that knockdown of LINC00115 could significantly inhibit the proliferation of lung cancer tissues in vivo. CONCLUSIONS: LINC00115 is highly expressed in lung cancer tissues, and knockdown of LINC00115 can significantly inhibit the proliferation and invasion of lung cancer, which provides a theoretical basis for the design of targeted molecules for the subsequent treatment of lung cancer.

TIPE2 Suppresses Malignancy of Pancreatic Cancer Through Inhibiting TGFß1 Mediated Signaling Pathway.

Pancreatic cancer is one of the major reasons of cancer-associated deaths due to poor diagnosis, high metastasis and drug resistance. Therefore, it is important to understand the cellular and molecular mechanisms of pancreatic cancer to identify new targets for the treatment. TIPE2 is an essential regulator of tumor apoptosis, inflammation and immune homeostasis. However, the role of TIPE2 is still not fully understood in pancreatic cancer. In this study, we found the expression of TIPE2 was decreased in pancreatic cancer tissues compare to paracancerous tissues, which was negatively correlated with tumor size in patients. Overexpression of TIPE2 significantly decreased cell proliferation, metastasis and increased apoptotic events in pancreatic cancer cell lines. Moreover, the results obtained from real time PCR and western blot revealed that TIPE2 was also involved in inhibiting MMPs and N-Cadherin expression while increasing Bax expression in pancreatic cancer cells. Similarly, TIPE2 could inhibit tumor growth in vivo, decrease the expression of Ki-67 and N-Cadherin, and increase the expression of Bax by IHC analysis in tumor tissues isolated from tumor-bearing mice. Mechanistic studies exhibited that TIPE2 might suppress pancreatic cancer development through inhibiting PI3K/AKT and Raf/MEK/ERK signaling pathways triggered by TGFß1. Moreover, the tumor-infiltrating lymphocytes from tumor-bearing mice were analyzed by flow cytometry, and showed that TIPE2 could promote T cell activation to exert an anti-tumor effect possibly through activation of DCs in a TGFß1 dependent manner. In general, we described the multiple regulatory mechanisms of TIPE2 in pancreatic tumorigenesis and tumor microenvironment, which suggested TIPE2 may act as a potential therapeutic target in pancreatic cancer.

B7-H3 on breast cancer cell MCF7 inhibits IFN-γ release from tumour-infiltrating T cells.

B7-H3 is a type I membrane protein that has contradictory co-stimulatory and co-inhibitory effects in adaptive and anti-tumour immunity. B7-H3 is up-regulated in many malignant tumours, including breast cancer. Therefore, we hypothesise that B7-H3, which has an immunosuppressive role, suppresses anti-tumour immunity. The aim of this study was to clarify the role of B7-H3 in the tumor microenvironment in breast cancer, explore the possibility of B7-H3 as a target for clinical immunotherapy, and provide reference for clinical work. We knocked down B7-H3 with siRNA in MCF7 breast cancer cells, which we termed MCF7-B7-H3-KD cells, and the expression of B7-H3 was assessed by flow cytometry. GAPDH (glyceraldehyde-3-phosphate dehydrogenase) knockdown was used as a control (MCF7-Gapdh). MCF7-B7-H3-KD and MCF7-Gapdh cells were co-cultured with peripheral blood mononuclear cells (PBMCs) and CD3+ T cells from healthy donors to assess the effect of B7-H3 loss. PBMCs cultured with MCF7-Gapdh cells showed decreased activation, proliferation, and function of CD8+ T cells, but there was no effect on the proliferation of CD4+ T cells. However, when MCF7-B7-H3-KD cells were co-cultured with PBMCs, the proliferation ability of CD4+ T cells and CD8+ T cells was significantly higher than that observed in MCF7-Gapdh cell co-culture. Additionally, co-culture with MCF7-Gapdh cells decreased the expression of IFN-γ (Interferon-γ). However, after co-culture with MCF7-B7-H3-KD cells, there was an increase in IFN-γ. We further found that this inhibitory effect on IFN-γ was because of decreased mTOR (the mammalian target of rapamycin) phosphorylation in T cells. Treatment of T cells co-cultured with MCF7-B7-H3-KD cells with an mTOR inhibitor blocked the secretion of IFN-γ. B7-H3 on tumour cells inhibits the proliferation of CD4+ and CD8+ T cells and inhibits the release of IFN-γ by decreasing mTOR signalling. A better understanding of these complex immune regulatory mechanisms should facilitate the generation of more powerful and selective tools to manipulate cancer therapy.

Altered miR-93-5p/miR-18a expression in serum for diagnosing non-small cell lung cancer.

OBJECTIVE: This research aimed at probing into miR-93-5p and miR-18a's diagnostic and prognostic values in non-small cell lung cancer (NSCLC) patients. METHODS: A total of 107 patients diagnosed with NSCLC in the Department of Oncology and Thoracic Surgery of our hospital from January 2015 to June 2016 were regarded as the research group (RG), and 42 healthy people were considered as the control group (CG). Serum samples were collected and miR-93-5p, miR-18a expression was detected via qPCR. The relationship between miR-93-5p, miR-18a and clinicopathological characteristics of NSCLC patients was assessed, and the diagnostic value of the two miRNAs was analyzed by ROC curve. RESULTS: miR-93-5p and miR-18a were up-regulated in NSCLC. The higher the degree of tumor differentiation, the higher the TNM stage and the expression of the two miRNAs were. The high expression was tied to tumor differentiation degree, TNM stage, lymph node metastasis and lymph-vascular space invasion (LVSI). The survival rate of miR-93-5p and miR-18a high expression patients was worse than that of those with low expression. The AUC value of both of the mRNAs in NSCLC diagnosis was high (0.8905). CONCLUSION: The expression of miR-93-5p and miR-18a is associated with NSCLC severity and prognosis, and both can be used as potential markers for diagnosis.

TYMSOS drives the proliferation, migration, and invasion of gastric cancer cells by regulating ZNF703 via sponging miR-4739.

Gastric cancer (GC) is a kind of malignancy originating from the epithelium of gastric mucosa. Long noncoding RNAs (lncRNAs) are tightly related to the GC progression. Herein, our research was meant to investigate a novel lncRNA thymidylate synthetase opposite strand (TYMSOS) in GC. Quantitative real-time polymerase chain reaction was used to analyze TYMSOS expression in GC cells. 5-Ethynyl-2'-deoxyuridine, flow cytometry analysis, and transwell assay detected the influence of TYMSOS on GC cell proliferation, apoptosis, migration, and invasion. Subcellular fractionation and fluorescent in situ hybridization assays determined the cellular localization of TYMSOS in GC cells. Bioinformatics programs, RNA-binding protein immunoprecipitation, RNA pull-down, and luciferase reporter assays measured the molecular interplays of TYMSOS in GC cells. In brief, TYMSOS was highly expressed in GC cells, and TYMSOS silence inhibited GC cell proliferation, migration, and invasion while elevating cell apoptosis. Functionally, TYMSOS functioned as a competing endogenous RNA to posttranscriptionally modulate GC progression. TYMSOS interacted with miR-4739 to regulate its target gene zinc finger protein 703. Collectively, our study proved the tumor-promoting role of TYMSOS in GC cells, which might offer the utility value for GC treatment.