[Impact of anemia on incidence of perioperative lower limb deep vein thrombosis in patients undergoing total hip arthroplasty].

Objective: To explore the impact of anemia on the incidence of perioperative lower limb deep vein thrombosis (DVT) in patients undergoing total hip arthroplasty (THA). Methods: A retrospective analysis was conducted on clinical data of 1 916 non-fracture patients who underwent THA between September 2015 and December 2021, meeting the selection criteria. Among them, there were 811 male and 1 105 female patients, aged between 18 and 94 years with an average of 59.2 years. Among the patients, 213 were diagnosed with anemia, while 1 703 were not. Preoperative DVT was observed in 55 patients, while 1 861 patients did not have DVT preoperatively (of which 75 patients developed new-onset DVT postoperatively). Univariate analysis was performed on variables including age, gender, body mass index (BMI), diabetes, hypertension, history of tumors, history of thrombosis, history of smoking, revision surgery, preoperative D-dimer positivity (≥0.5 mg/L), presence of anemia, operation time, intraoperative blood loss, transfusion requirement, and pre- and post-operative levels of red blood cells, hemoglobin, hematocrit, and platelets. Furthermore, logistic regression was utilized for multivariate analysis to identify risk factors associated with DVT formation. Results: Univariate analysis showed that age, gender, hypertension, revision surgery, preoperative levels of red blood cells, preoperative hemoglobin, preoperative D-dimer positivity, and anemia were influencing factors for preoperative DVT ( P<0.05). Further logistic regression analysis indicated that age (>60 years old), female, preoperative D-dimer positivity, and anemia were risk factors for preoperative DVT ( P<0.05). Univariate analysis also revealed that age, female, revision surgery, preoperative D-dimer positivity, anemia, transfusion requirement, postoperative level of red blood cells, and postoperative hemoglobin level were influencing factors for postoperative new-onset DVT ( P<0.05). Further logistic regression analysis indicated that age (>60 years old), female, and revision surgery were risk factors for postoperative new-onset DVT ( P<0.05). Conclusion: The incidence of anemia is higher among patients with preoperative DVT for THA, and anemia is an independent risk factor for preoperative DVT occurrence in THA. While anemia may not be an independent risk factor for THA postoperative new-onset DVT, the incidence of anemia is higher among patients with postoperative new-onset DVT.

Calcium signals and potential therapy targets in ovarian cancer (Review).

Ovarian cancer (OC) is a deadly disease. The poor prognosis and high lethality of OC are attributed to its high degrees of aggressiveness, resistance to chemotherapy and recurrence rates. Calcium ion (Ca2+) signaling has received attention in recent years, as it appears to form an essential part of various aspects of cancer pathophysiology and is a potential therapeutic target for OC treatment. Disruption of normal Ca2+ signaling pathways can induce changes in cell cycle progression, apoptosis, proliferation and migration and invasion, leading to the development of the malignant phenotype of tumors. In the present review, the main roles of ion channel/receptor/pump­triggered Ca2+ signaling pathways located at the plasma membrane and organelle Ca2+ transport in OC are summarized. In addition, the potential of Ca2+ signaling as a novel target for the development of effective treatment strategies for OC was discussed. Furthering the understanding into the role of Ca2+ signaling in OC is expected to facilitated the identification of novel therapeutic targets and improved clinical outcomes for patients.

Association between intake of the n-3 polyunsaturated fatty acid docosahexaenoic acid (n-3 PUFA DHA) and reduced risk of ovarian cancer: A systematic Mendelian Randomization study.

BACKGROUND & AIMS: Whether the intake of docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, is beneficial for ovarian cancer (OC) remains controversial and we hope to disentangle this puzzle using genetic data from large-scale populations in European and Asian. METHODS: We employed, for the first time, a systematic Mendelian randomization (MR) design to comprehensively evaluate the causal effect of plasma DHA levels, an objective biomarker of DHA intake, on OC risk in European and then verified the extrapolation of the results in the Asian. Data in the analysis included genetic association data obtained from large-scale genome-wide association studies with 13,499 individuals for plasma DHA measurements and 66,450 individuals for OC in the European population, and 1361 individuals for plasma DHA measurements and 61,457 individuals for OC in the Asian population. The causal relationship between DHA and OC was estimated using the inverse-variance weighted approach, together with extensive validation and sensitivity analyses to verify the main results. RESULTS: In the European population, MR evidence suggested a causal relationship between higher plasma DHA levels and lower OC risk (OR, 0.89 for OC per one-SD increment in DHA; 95% CI, 0.83 to 0.96; P = 0.003). Subgroup analysis by histological type of OC indicated that this observed association was stronger among endometrioid ovarian cancer (EOC) (OR, 0.82; 95% CI, 0.69 to 0.96; P = 0.014). A similar causal association of borderline significance was reached in the Asian replication set. The above results were consistently supported by a series of validation and sensitivity analyses. CONCLUSION: Our study provided robust genetic evidence for a protective association between plasma DHA levels and lower risk of OC, especially EOC, in the European population. These findings may inform prevention strategies and interventions directed towards DHA intake and OC.

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.

Insight into the causality between basal metabolic rate and endometrial and ovarian cancers: Analysis utilizing systematic Mendelian randomization and genetic association data from over 331,000 UK biobank participants.

BACKGROUND: Observational studies have demonstrated that basal metabolic rate (BMR) is associated with the risk of endometrial cancer (EC) and ovarian cancer (OC). However, it is unclear whether these associations reflect a causal relationship. OBJECTIVE: To reveal the causality between BMR and EC and OC, we performed the first comprehensive two-sample Mendelian randomization (MR) analyses. METHODS: Genetic variants were used as proxies of BMR. GWAS summary statistics of BMR, EC and OC were obtained from the UK Biobank Consortium, Endometrial Cancer Association Consortium and Ovarian Cancer Association Consortium respectively. The inverse variance weighted method was employed as the main approach for MR analysis. A series of sensitivity analyses were implemented to validate the robustness and reliability of the results. RESULTS: BMR was significantly related to an increased risk of EC (ORSD  = 1.49; 95% CI: 1.29-1.72; p-Value < .001) and OC (ORSD  = 1.21; 95% CI: 1.08-1.35; p-Value < .001). Furthermore, the stratified analysis indicated that BMR was positively associated with endometrioid endometrial cancer (EEC) (ORSD  = 1.45; 95% CI, 1.23-1.70; p-Value < .001), clear cell ovarian cancer(CCOC) (ORSD  = 1.89; 95% CI:1.35-2.64; p-Value < .001) and endometrioid ovarian cancer risk (EOC) (ORSD  = 1.45; 95% CI: 1.12-1.88; p-Value = .005). However, there were no significant associations of BMR with invasive mucinous ovarian cancer (IMOC), high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC). The robustness of the above results was further verified in sensitivity analyses. CONCLUSION: The MR study provided etiological evidence for the positive association of BMR with the risk of EC, EEC, OC, CCOC and EOC. But this study did not provide enough evidence suggesting the causal associations of BMR with IMOC, HGSOC and LGSOC.

Identification of Hub Genes for Colorectal Cancer with Liver Metastasis Using miRNA-mRNA Network.

Background: Liver metastasis is an important cause of death in patients with colorectal cancer (CRC). Increasing evidence indicates that microRNAs (miRNAs) are involved in the pathogenesis of colorectal cancer liver metastasis (CRLM). This study is aimed at exploring the potential miRNA-mRNA regulatory network. Methods: From the GEO database, we downloaded the microarray datasets GSE56350 and GSE73178. GEO2R was used to conduct differentially expressed miRNAs (DEMs) between CRC and CRLM using the GEO2R tool. Then, GO and KEGG pathway analysis for differentially expressed genes (DEGs) performed via DAVID. A protein-protein interaction (PPI) network was constructed by the STRING and identified by Cytoscape. Hub genes were identified by miRNA-mRNA network. Finally, the expression of the hub gene expression was assessed in the GSE81558. Results: The four DEMs (hsa-miR-204-5p, hsa-miR-122-5p, hsa-miR-95-3p, and hsa-miR-552-3p) were identified as common DEMs in GSE56350 and GSE73178 datasets. The SP1 was likely to adjust the upregulated DEMs; however, the YY1 could regulate both the upregulated and downregulated DEMs. A total of 3925 genes (3447 upregulated DEM genes and 478 downregulated DEM genes) were screened. These predicted genes were mainly linked to Platinum drug resistance, Cellular senescence, and ErbB signaling pathway. Through the gene network construction, most of the hub genes were found to be modulated by hsa-miR-204-5p, hsa-miR-122-5p, hsa-miR-95-3p, and hsa-miR-552-3p. Among the top 20 hub genes, the expression of CREB1, RHOA, and EGFR was significantly different in the GSE81558 dataset. Conclusion: In this study, miRNA-mRNA networks in CRLM were screened between CRC patients and CRLM patients to provide a new method to predict for the pathogenesis and development of CRC.

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.

Recent Developments on the Roles of Calcium Signals and Potential Therapy Targets in Cervical Cancer.

Intracellular calcium (Ca2+) concentration ([Ca2+]i) is implicated in proliferation, invasion, and metastasis in cancerous tissues. A variety of oncologic therapies and some candidate drugs induce their antitumor effects (in part or in whole) through the modulation of [Ca2+]i. Cervical cancer is one of most common cancers among women worldwide. Recently, major research advances relating to the Ca2+ signals in cervical cancer are emerging. In this review, we comprehensively describe the current progress concerning the roles of Ca2+ signals in the occurrence, development, and prognosis of cervical cancer. It will enhance our understanding of the causative mechanism of Ca2+ signals in cervical cancer and thus provide new sights for identifying potential therapeutic targets for drug discovery.

Synergism between the metabolic syndrome components and cancer incidence: results from a prospective nested case-control study based on the China Health and Retirement Longitudinal Study (CHARLS).

OBJECTIVES: Synergism between the metabolic syndrome (MetSyn) components and cancer incidence still remains inconclusive. We aimed to investigate the unique or joint role of MetSyn components in cancer onset. DESIGN: We conducted a prospective nested case-control study based on the China Health and Retirement Longitudinal Study. SETTING: An ongoing national representative longitudinal study included follow-up survey of people aged 45 years and older and their partners living in private households in China. PARTICIPANTS: There were 17 708 individuals included at baseline. A total of 306 incident cancers was identified during the follow-up. For every case, we used incidence-density sampling to match three concurrent cancer-free controls by age, sex, and both duration and calendar time of follow-up. Exposure of interest was any MetSyn diagnosis at baseline. RESULTS: We observed elevation in cancer risk associated with MetSyn in a significant way when the number of MetSyn components was over three (OR: 1.88; 95% CI: 1.19 to 2.97), or when components contained any of elevated triglycerides (OR: 1.61; 95% CI: 1.05 to 2.48), reduced high-density lipoprotein (HDL) cholesterol (OR: 2.33; 95% CI: 1.40 to 3.86) or elevated blood pressure (OR: 1.65; 95% CI: 1.04 to 2.59) after consistent multiple adjustments in different models. The highest cancer risk was in the female reproductive system and breast cancer (OR: 4.22; 95% CI: 1.62 to 10.95) followed by digestive system (OR: 1.67; 95% CI: 1.11 to 2.53). Sensitivity analyses showed similar results after first follow-up was excluded. However, any unique MetSyn component was not associated with increased cancer risk. Interestingly, the reduced HDL was observed to be widely associated with over twofold increased risk of cancer, only when together with other MetSyn components. CONCLUSION: MetSyn components, in a collaborative manner rather than its unique component, were associated with elevated cancer risk. Not only obesity but even subtle metabolic disturbances may give rise to cancer.

Comparing Long-Term Survival Outcomes for Muscle-Invasive Bladder Cancer Patients Who Underwent with Radical Cystectomy and Bladder-Sparing Trimodality Therapy: A Multicentre Cohort Analysis.

Background: Although radical cystectomy (RC) is the clinical practice guideline-recommended treatment of muscle-invasive bladder cancer (MIBC), bladder-sparing trimodality therapy (TMT) has emerged as a valid treatment option. Findings comparing the survival outcomes for MIBC patients who underwent RC and TMT are inconclusive. Objective: We designed a large hospital-based multicohort study to compare the effectiveness of TMT with RC. Methods: Information on deaths was jointly retrieved from EMR (electronic medical record), cause of death registry, and chronic disease surveillance as well as study-specific questionnaire. To avoid the systematical difference between patients who received two modalities, RC-MIBC cohort was propensity score-matched to TMT-MIBC cohort, and the Cox proportional hazard regression was used to calculate the overall survival (OS) and disease-specific survival (DSS). Results: There were 891 MIBC patients treated with RC and another 891 MIBC patients who underwent with TMT in the propensity score matching. Comparable effectiveness between two modalities was observed for DSS (HR, 1.20; 95% confidence interval (CI), 0.94 to 1.49) and OS (HR, 1.17; 95% CI, 0.91 to 1.43) according to multiple adjustment after a median follow-up of approximately 9.3 years. However, a relatively higher mortality rate around 5 years after TMT treatment was found compared to RC (HR, 1.26; 95% CI, 1.01 to 1.53). The respective 5-year OS rates were 69% and 73% for TMT cohort and RC cohort, respectively. Conclusions: Our findings supported that MIBC patients with TMT yielded survival outcomes comparable to MIBC patients who underwent RC overall. Treatment options should be suggested considering patients' age and willingness.

Hormone replacement therapy in relation to the risk of colorectal cancer in women by BMI: a multicentre study with propensity score matching.

BACKGROUND: Epidemiological evidence about hormone replacement therapy and colorectal carcinogenesis by demographic and clinical traits remains unclear. We aimed to assess this postulated association in a large multicentre study and further explore the modification effect by BMI and others. METHODS: We retrospectively collected records of women diagnosed with colorectal cancer (CRC) at the age of 50 years and older during 2014-2017 and their HRT dispensing prior to CRC diagnosis in three tertiary hospitals in China. CRC cases were matched with controls at a ratio of 1:3 using nearest neighbour propensity scores matching to better control for the remaining imbalance between groups, which generated a total of 824 cases with 2472 controls. RESULTS: Our study confirmed the inversed association between colorectal cancer risk and hormone replacement therapy (OR, 0.62; 95% CI, 0.54-0.75), which was more prominent among women having multiple HRT dispenses (OR, 0.60; 95% CI, 0.52-0.76). Furthermore, significant associations were consistently observed for the short-term (OR, 0.69; 95% CI, 0.57-0.88), middle-term (OR, 0.51; 95% CI, 0.41-0.66), and long-term HRT users (OR, 0.70; 95% CI, 0.43-0.90). Estrogen-related regimen reduced CRC risk more than progestogen-only. We, for the first time, found that the modifying effect of BMI on HRT use and CRC risk was in different ways when BMI was categorized by a medium level of 27. CONCLUSION: Our findings mainly suggest that there might be a different mechanism for the reversed association between HRT and colorectal tumorigenesis by BMI level, providing thoughts on clinical treatment of CRC.

Effect of 1α,25(OH)2D3-Treated M1 and M2 Macrophages on Cell Proliferation and Migration Ability in Ovarian Cancer.

The biological active form of vitamin D3, 1α,25-dehydroxyvitamin D3 [1α,25(OH)2D3], exerts pleiotropic effects including bone mineralization, anti-tumor, as well as immunomodulator. This study aimed to explore the potential impact of 1α,25(OH)2D3 on tumor-associated macrophages (TAMs) infiltration in ovarian cancer. Firstly, human monocytic THP-1 cells were differentiated into macrophages (M0) in the presence of phorbol 12-myristate 13-acetate (PMA). In Vivo, 1α,25(OH)2D3 not only reversed the polarization of M2 macrophages, but also decreased the proliferation and migration abilities of ovarian cancer cells induced by M2 macrophages supernatant. Furthermore, 1α,25(OH)2D3 dramatically decreased the secretion of TGF-ß1 and MMP-9 in M2 macrophages. However, no significant effect was observed in 1α,25(OH)2D3 treated M1 macrophages. In Vivo, vitamin D3 had an inhibitive effect of 1α,25(OH)2D3-treated M2 macrophages on tumorigenesis. In addition, we conducted the association of TAMs with the poor prognosis of patients with ovarian cancer by meta-analysis, which suggested the higher proportion of M2 macrophages was related to the poorer prognosis in ovarian cancer. Collectively, these results identified distinct roles of 1α,25(OH)2D3 treated M1 and M2 macrophages on cell proliferation and migration abilities in ovarian cancer.

MicroRNA-155-5p promotes cell proliferation and invasion in lung squamous cell carcinoma through negative regulation of fibroblast growth factor 9 expression.

BACKGROUND: Non-small cell lung cancer (NSCLC) ranks first for mortality among all malignancies. Squamous cell carcinoma (SCC) is one of the main types of NSCLC. Previous studies have found that fibroblast growth factor 9 (FGF9) is closely related to lung SCC via different molecular regulatory mechanisms. This study aimed to explore the relationship between microRNA-155-5p (miR-155-5p) and FGF9 gene expression and their effects on the proliferation and invasion of lung SCC through experiments, in order to provide theoretical basis for overcoming this disease. METHODS: Fluorescence quantitative polymerase chain reaction was employed for the detection miR-155-5p and FGF9 expression in lung SCC tissues (n=40) and the corresponding adjacent normal tissues. The expression of FGF9 in the cancerous and adjacent tissues was detected by western blot. Transwell assay used to verify the effect of miR-155-5p on FGF-induced invasion and migration. Finally, subcutaneous tumor formation experiments in nude mice were used to verify how miR-155-5p and FGF9 affect the proliferative ability of lung SCC cells. RESULTS: The results of fluorescence quantitative PCR revealed that miR-155-5p and FGF9 were expressed at high and low levels, respectively, in lung SCC tissue samples relative to normal adjacent tissue samples. Western blot analysis of 6 lung SCC tissue samples revealed a significantly reduced level of FGF9. Correlation analysis uncovered that miR-155-5p and FGF9 share a significant negative correlation in lung SCC. At the messenger RNA and protein levels miR-155-5p could negatively regulate the expression of FGF9. Bioinformatics and dual luciferase reporter assay results confirmed FGF9 to be a downstream regulatory gene targeted by miR-155-5p. Our in vitro and in vivo results demonstrated that FGF9 overexpression exerted a significant inhibitory effect on miR-155-5p's ability to promote lung cancer cell growth, invasion, and proliferation. CONCLUSIONS: Our results show that miR-155-5p, as an oncogene, negative regulates FGF9 expression to promote SCC occurrence and development in the lungs.

Risk of Death in Colorectal Cancer Patients with Multi-morbidities of Metabolic Syndrome: A Retrospective Multicohort Analysis.

PURPOSE: The prevalence of multi-morbidities with colorectal cancer (CRC) is known to be increasing. Particularly prognosis of CRC patients co-diagnosed with metabolic syndrome (MetSyn) was largely unknown. We aimed to examine the death risk of CRC patients according to the multiple MetSyn morbidities. MATERIALS AND METHODS: We identified CRC patients with MetSyn from the electronic medical records (EMR) systems in five independent hospitals during 2006-2011. Information on deaths was jointly retrieved from EMR, cause of death registry and chronic disease surveillance as well as study-specific questionnaire. Cox proportional hazards regression was used to calculate the overall and CRC-specific hazards ratios (HR) comparing MetSyn CRC cohort with reference CRC cohort. RESULTS: A total of 682 CRC patients in MetSyn CRC cohort were identified from 24 months before CRC diagnosis to 1 month after. During a median follow-up of 92 months, we totally observed 584 deaths from CRC, 245 being in MetSyn cohort and 339 in reference cohort. Overall, MetSyn CRC cohort had an elevated risk of CRC-specific mortality (HR, 1.49; 95% confidence interval [CI], 1.07 to 1.90) and overall mortality (HR, 1.43; 95% CI, 1.09 to 1.84) compared to reference cohort after multiple adjustment. Stratified analyses showed higher mortality risk among women (HR, 1.87; 95% CI, 1.04 to 2.27) and specific components of MetSyn. Notably, the number of MetSyn components was observed to be significantly related to CRC prognosis. CONCLUSION: Our findings supported that multi-morbidities of MetSyn associated with elevated death risk after CRC. MetSyn should be considered as an integrated medical condition more than its components in CRC prognostic management.

Enhanced lysosomal function is critical for paclitaxel resistance in cancer cells: reversed by artesunate.

The mechanism underlying the resistance of cancer cells to chemotherapeutic drug varies with different cancer cells. Recent evidence shows that lysosomal function is associated with drug resistance of cancer cells. Artesunate, a derivative of artemisinin, displays broad antitumor activity and direct cytotoxicity on various tumor cells. Our previous study shows that artesunate increases autophagosome accumulation, while significantly decreases autolysosome number in cancer cells, suggesting that artesunate might impair the lysosomal function. In this study, we investigated the effects of artesunate on lysosomal function and its relationship with chemotherapeutic drug resistance in cancer cells. We found that the lysosomal function was significantly enhanced in two drug-resistant (A549/TAX and A549/DDP) cells. Furthermore, we showed that the enhanced lysosomal function by overexpression of transcription factor EB (TFEB) significantly increased MCF-7 cells resistance to doxorubicin (DOX), whereas the decreased lysosomal function by TFEB-knockdown or lysosome inhibitor chloroquine increased MCF-7 cells sensitivity to DOX. Treatment of A549/TAX cells with artesunate (2.5-50 µM) dose-dependently inhibited lysosomal function and the clearance of dysfunctional mitochondria, and induced cell apoptosis. Moreover, we demonstrated that artesunate exerted more potent inhibition on the resistant (A549/TAX and MCF-7/ADR) cells with higher activity of lysosomal function. Our results suggest that artesunate or other inhibitors of lysosomal function would be potential in the treatment of cancer cells with drug resistance caused by the enhanced lysosomal function.

LncRNA NUTM2A-AS1 positively modulates TET1 and HIF-1A to enhance gastric cancer tumorigenesis and drug resistance by sponging miR-376a.

Long noncoding RNA NUTM2A-AS1 has been shown to be dysregulated in non-small cell lung carcinoma. To date, it is unclear whether NUTM2A-AS1 plays a role in gastric cancer progression. The purpose of this study is to elucidate the molecular mechanism of the role of NUTM2A-AS1 in gastric cancer. mRNA and protein levels were measured by RT-qPCR and western blot methods. Invasion ability was examined by transwell assay. Cell viability was determined by MTT assay. Dual-luciferase assay, RNA pull down, and RNA immunoprecipitation were used to confirm direct binding of between miR-376a and NUTM2A-AS1 or TET1. Xenografting tumor assay and TCGA analysis showed the contributory role of NUTM2A-AS1 in vivo and human clinical setting. Our results suggested that NUTM2A-AS1 promoted cell viability, invasion, and drug resistance of gastric cancer cells, which was largely rescued by miR-376a. More interestingly, TET1 and HIF-1A were negatively regulated by miR-376a. TET1 could interact with HIF-1A to modulate PD-L1. Finally, we revealed that PD-L1 was key to NUTM2A-AS1- and miR-376a-mediated tumorigenesis and drug resistance. In summary, our conclusions facilitate us understand the underlying mechanism and develop novel treatment strategy for gastric cancer.

Expression and clinical significance of PD-L1 and c-Myc in non-small cell lung cancer.

BACKGROUND: It is known that there are insufficient prognostic factors for non-small cell lung cancer (NSCLC). It was reported that PD-L1 was a prognostic factor for NSCLC,and c-Myc regulated the expression of PD-L1. Herein, we investigated c-Myc and PD-L1 expression and their association with overall survival (OS) in NSCLC. METHODS: Formalin-fixed paraffin-embedded specimens were obtained from 128 patients with surgically resected primary NSCLC. Immunohistochemistry was used to assess the expression of PD-L1 and c-Myc in this study. Pearson's Chi squared test or Fisher's exact test was used to analyze the correlation of the expression of PD-L1 and c-Myc with clinicopathologic features. The relationship between OS and the expression of PD-L1 and c-Myc was evaluated by the Kaplan-Meier method and Cox proportional hazards model, respectively. RESULTS: Positive expression of PD-L1 was detected in 59 patients (46.1%). Patients with negative expression of PD-L1 had remarkably longer OS than those with positive expression of PD-L1. The positive expression rate of c-Myc in NSCLC accounted for 58.6% (75/128) and its expression was significantly more frequent in males (p = 0.002) and patients with lymph node metastasis (p = 0.029). PD-L1 expression was positively correlated with c-Myc expression (r = 0.459, p < 0.001). The PD-L1 and c-Myc double-positive group had a worse prognosis than other subgroups (p < 0.05), and the PD-L1 and c-Myc double-negative group had a better OS than other subgroups (p < 0.05). CONCLUSION: Conjoint analysis of the expression of PD-L1 and c-Myc was a better prognostic approach for NSCLC patients.

Chemotherapy combined with dendritic cell vaccine and cytokine-induced killer cells in the treatment of colorectal carcinoma: a meta-analysis.

AIM: To investigate the efficacy and safety of dendritic cell (DC) vaccine combined with cytokine-induced killer (CIK) cell therapy in colorectal carcinoma (CRC). PATIENTS AND METHODS: PubMed, Embase, and Cochrane Library databases were searched systematically for clinical trials of DC vaccine and CIK cell therapy combined with chemotherapy for CRC. The primary and secondary endpoints were overall survival (OS) and disease-free survival (DFS), respectively. Pooled risk ratios were used to assess the treatment efficacy. Both random and fixed effects models were used for statistical analysis. The study population consisted of 871 CRC patients enrolled in four trials. RESULTS: OS and DFS were significantly improved in patients who received chemotherapy combined with DC vaccine and CIK cells, and no severe adverse events were shown. CONCLUSIONS: The study demonstrated that the addition of DC vaccine and CIK cell therapy to chemotherapy is feasible and effective in patients with CRC.

Knockdown of Arf6 increases drug sensitivity and inhibits proliferation, migration and invasion in gastric cancer SGC-7901 cells.

ADP-ribosylation factor 6 (Arf6), a member of the ADP-ribosylation factor family, is overexpressed in different types of cancer cell and promotes invasion, metastasis and drug resistance. However, the potential functions of Arf6 in gastric cancer (GC), and the molecular mechanism underlying these functions, remain to be fully elucidated. In the present study, the results demonstrated that in vitro knockdown of Arf6 decreased proliferation, colony formation, migration and invasion in SGC-7901 cells. Arf6 knockdown also markedly decreased the activity of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Furthermore, knockdown of Arf6 was associated with elevated chemosensitivity of SGC-7901 cells to 5-fluorouracil through inactivation of the ERK1/2 signaling pathway. Taken together, these results suggest that Arf6 is involved in regulating proliferation, migration, invasion and drug resistance in GC, and may be a potential therapeutic target for the treatment of GC.

Application of contrast-enhanced ultrasonography after radiofrequency ablation for renal cell carcinoma: is it sufficient for assessment of therapeutic response?

PURPOSE: To assess the efficacy of contrast-enhanced ultrasonography (CEUS) with Sonovue in the evaluation of therapeutic response to radiofrequency ablation (RFA) of renal cell carcinoma (RCC). MATERIALS AND METHODS: In a recent 3 years, 63 patients (mean age, 60 years; range 26-81 years) with 64 RCCs were treated by RFA. The lesions had a diameter between 1.8 and 9.8 cm (average diameter, 3.1 cm). The indications for RFA treatment included chronic renal insufficiency (n = 10), presence of solitary kidney (n =3), bilateral renal carcinoma (BRCC) (n =2), advanced age (n =12), significant medical comorbidity (n =29) or refusal of conventional therapy (n =7). Tumors were treated by laparoscopy-assisted (n =41), open surgical (n =18) or percutaneous US guidance (n =4). Follow-up CEUS and contrast-enhanced CT were performed 1 month after treatment to assess the necrotic area. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor. RESULTS: On the 1-month CEUS and CT imaging after RFA, 62 of 64 tumors (96.9%) were successfully ablated with one session, and residual tumors were found in two RCCs. One of the two tumors was subjected to additional RFA treatment. We could not obtain a complete ablation in the other tumor of a patient with solitary kidney. The diagnostic concordance between the CEUS and 1-month follow-up CT was 100%. Sixty-one patients survived in the follow-up phase which ranged from 2 to 34 months. One patient with solitary kidney died of systemic disease progression and one patient was lost to follow-up. Of the 61 tumors without residual on both CT and CEUS after RFA, four had suspicious findings of recurrence on follow-up CEUS, and two of them were confirmed by subsequent CT examination. With CT as the reference imaging procedure in the assessment of renal tumor ablation, the sensitivity, specificity, positive predictive value, and negative predictive value of CEUS for detecting recurrence during follow-up were 100%, 96.6%, 50%, and 100%. CONCLUSION: Despite its limitation of false-positive value, CEUS is potentially effective in assessing the therapeutic response to RFA of RCC.