Ginsenoside 20(S)-Rg3 reduces KIF20A expression and promotes CDC25A proteasomal degradation in epithelial ovarian cancer.

Background: Ginsenoside 20(S)-Rg3 shows promising tumor-suppressive effects in ovarian cancer via inhibiting NF-κB signaling. This study aimed to explore the downstream tumor suppressive mechanisms of ginsenoside Rg3 via this signaling pathway. Materials and methods: A systematical screening was applied to examine the expression profile of 41 kinesin family member genes in ovarian cancer. The regulatory effect of ginsenoside Rg3 on KIF20A expression was studied. In addition, we explored interacting proteins of KIF20A and their molecular regulations in ovarian cancer. RNA-seq data from The Cancer Genome Atlas (TCGA) was used for bioinformatic analysis. Epithelial ovarian cancer cell lines SKOV3 and A2780 were used as in vitro and in vivo cell models. Commercial human ovarian cancer tissue arrays were used for immunohistochemistry staining. Results: KIF20A is a biomarker of poor prognosis among the kinesin genes. It promotes ovarian cancer cell growth in vitro and in vivo. Ginsenoside Rg3 can suppress the transcription of KIF20A. GST pull-down and co-immunoprecipitation (IP) assays confirmed that KIF20A physically interacts with BTRC (ß-TrCP1), a substrate recognition subunit for SCFß-TrCP E3 ubiquitin ligase. In vitro ubiquitination and cycloheximide (CHX) chase assays showed that via interacting with BTRC, KIF20A reduces BTRC-mediated CDC25A poly-ubiquitination and enhances its stability. Ginsenoside Rg3 treatment partly abrogates KIF20A overexpression-induced CDC25A upregulation. Conclusion: This study revealed a novel anti-tumor mechanism of ginsenoside Rg3. It can inhibit KIF20A transcription and promote CDC25A proteasomal degradation in epithelial ovarian cancer.

Prognostic value of sarcopenia in patients with lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors or immune checkpoint inhibitors.

Objectives: It remains controversial whether sarcopenia has any significant impact on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Therefore, in this study, we aimed to assess the association between sarcopenia and clinical outcomes in patients with advanced NSCLC receiving EGFR-TKIs or ICIs as a first-line therapy. Methods: We retrospectively enrolled 131 patients with advanced NSCLC treated with first-line EGFR-TKIs or ICIs between 1 March 2019 and 31 March 2021. To estimate sarcopenia, we calculated skeletal muscle index (SMI) as the ratio of skeletal muscle area (cm2) to height squared (m2). Associations between sarcopenia and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and log-rank tests, respectively. A Cox proportional hazards regression model was used to assess the factors associated with OS and PFS. The Student's t-test or Mann-Whitney U test was used to compare the SMI between patients with or without objective response and disease control. The chi-squared test was used to compare adverse events (AEs) between patients with and without sarcopenia. Results: Among the 131 patients, 35 (26.7%) were diagnosed with sarcopenia. Sarcopenia was an independent predictor of poor OS and PFS (p < 0.05) overall and in the EGFR-TKI- and ICI-treated cohorts. Among all patients, those with sarcopenia showed significantly shorter OS and PFS than those without sarcopenia (median OS and PFS: 13.0 vs. 26.0 months and 6.4 vs. 15.1 months; both p < 0.001). These associations were consistent across the subtypes of most clinical characteristics. Statistically significant differences between the objective response (OR) and non-OR groups were also observed in the mean SMI (OR group, 43.89 ± 7.55 vs. non-OR group, 38.84 ± 7.11 cm2/m2; p < 0.001). In addition, we observed similar results with disease control (DC) and non-DC groups (DC group, 42.46 ± 7.64 vs. non-DCR group, 33.74 ± 4.31 cm2/m2; p < 0.001). The AEs did not differ significantly between the sarcopenia and non-sarcopenia groups. Conclusion: Sarcopenia before treatment might be a significant predictor of poor clinical outcomes (shorter OS and PFS, fewer ORs, less DC) in patients with advanced NSCLC treated with EGFR-TKIs or ICIs as the first-line therapy.

Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer.

BACKGROUND: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual. METHODS: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. RESULTS: A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial. CONCLUSIONS: As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.

Ginsenoside Rg5 enhances the radiosensitivity of lung adenocarcinoma via reducing HSP90-CDC37 interaction and promoting client protein degradation.

Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects. This study aimed to explore its radio-sensitizing effects and the underlying mechanisms. Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis. Bioinformatic molecular docking prediction and following validation by surface plasmon resonance (SPR) technology, cellular thermal shift assay (CETSA), and isothermal titration calorimetry (ITC) were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha (HSP90α). The effects of ginsenoside Rg5 on HSP90-cell division cycle 37 (CDC37) interaction, the client protein stability, and the downstream regulations were further explored. Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis. It could bind to HSP90α with a high affinity, but the affinity was drastically decreased by HSP90α Y61A mutation. Co-immunoprecipitation (Co-IP) and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner. It reduced irradiation-induced upregulation of the HSP90-CDC37 client proteins, including SRC, CDK4, RAF1, and ULK1 in A549 cell-derived xenograft (CDX) tumors. Ginsenoside Rg5 or MRT67307 (an IKKε/TBK1 inhibitor) pretreatment suppressed irradiation-induced elevation of the LC3-II/ß ratio and restored irradiation-induced downregulation of p62 expression. In A549 CDX tumors, ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage. In conclusion, ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90α and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.

Post-treatment serum triglyceride: An effective biomarker for body fat mass and overall survival in esophageal squamous cell cancer patients treated with chemoradiotherapy.

Objectives: Although lipids have been assessed for their possible roles in cancer survival prediction, studies on the association between serum triglyceride (TG) levels and the prognosis of esophageal squamous cell carcinoma (ESCC) patients are limited. This study aimed to evaluate whether serum TG is associated with outcomes in patients with ESCC and investigate any interaction between serum TG and clinical parameters, especially body fat mass. Materials and methods: We conducted a prospective case study on patients diagnosed with ESCC between March 2012 and November 2018. We measured patients' serum TG levels before and after treatment. The association between serum TG and overall survival (OS) was evaluated using hazard ratios. We sought to determine a threshold point using optimal stratification. Survival analysis was performed using Kaplan-Meier curves and a Cox proportional hazards model. Results: Of the 257 participants diagnosed with ESCC, 200 (77.8%) were men. Median follow-up time was 22.4 months (range 3.3-92.4 months). Using univariate Cox proportional hazard analysis and subsequent multivariate analysis, post-TG levels, Karnofsky performance scores, T stages, and chemotherapy cycles were shown to be independent prognostic factors for OS (p < 0.05). The post-TG cut-off point to best classify patients with respect to time to mortality was 1.47 mmol/L. A post-TG level of ≥ 1.47 mmol/L could independently predict a better OS (hazard ratio: 0.55, 95% confidence interval: 0.37-0.79). The associations were consistent across the subtypes of clinical parameters. Furthermore, the post-body mass index, post-subcutaneous adipose tissue area, post-visceral adipose tissue area, post-total adiposity tissue area, and post-total adipose density exhibited a strong positive association with post-TG levels. Conclusion: Post-TG levels were found to be a significant positive prognostic biomarker for body fat mass and OS in ESCC patients.

Establishment of predictive nomogram and web-based survival risk calculator for malignant pleural mesothelioma: A SEER database analysis.

Background: Malignant pleural mesothelioma (MPM) is an uncommon condition with limited available therapies and dismal prognoses. The purpose of this work was to create a multivariate clinical prognostic nomogram and a web-based survival risk calculator to forecast patients' prognoses. Methods: Using a randomization process, training and validation groups were created for a retrospective cohort study that examined the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 for individuals diagnosed with MPM (7:3 ratio). Overall survival (OS) and cancer-specific survival (CSS) were the primary endpoints. Clinical traits linked to OS and CSS were identified using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis, which was also utilized to develop nomogram survival models and online survival risk calculators. By charting the receiver operating characteristic (ROC), consistency index (C-index), calibration curve, and decision curve analysis (DCA), the model's performance was assessed. The nomogram was used to classify patients into various risk categories, and the Kaplan-Meier method was used to examine each risk group's survival rate. Results: The prognostic model comprised a total of 1978 patients. For the total group, the median OS and CSS were 10 (9.4-10.5) and 11 (9.4-12.6) months, respectively. As independent factors for OS and CSS, age, gender, insurance, histology, T stage, M stage, surgery, and chemotherapy were chosen. The calibration graphs demonstrated good concordance. In the training and validation groups, the C-indices for OS and CSS were 0.729, 0.717, 0.711, and 0.721, respectively. Our nomogram produced a greater clinical net benefit than the AJCC 7th edition, according to DCA and ROC analysis. According to the cut-off values of 171 for OS and 189 for CSS of the total scores from our nomogram, patients were classified into two risk groups. The P-value < 0.001 on the Kaplan-Meier plot revealed a significant difference in survival between the two patient groups. Conclusions: Patient survival in MPM was correctly predicted by the risk evaluation model. This will support clinicians in the practice of individualized medicine.

Ginsenoside Rg3 increases gemcitabine sensitivity of pancreatic adenocarcinoma via reducing ZFP91 mediated TSPYL2 destabilization.

Background: Ginsenoside Rg3 and gemcitabine have mutual enhancing antitumor effects. However, the underlying mechanisms are not clear. This study explored the influence of ginsenoside Rg3 on Zinc finger protein 91 homolog (ZFP91) expression in pancreatic adenocarcinoma (PAAD) and their regulatory mechanisms on gemcitabine sensitivity. Methods: RNA-seq and survival data from The Cancer Genome Atlas (TCGA)-PAAD and Genotype-Tissue Expression (GTEx) were used for in-silicon analysis. PANC-1, BxPC-3, and PANC-1 gemcitabine-resistant (PANC-1/GR) cells were used for in vitro analysis. PANC-1 derived tumor xenograft nude mice model was used to assess the influence of ginsenoside Rg3 and ZFP91 on tumor growth in vivo. Results: Ginsenoside Rg3 reduced ZFP91 expression in PAAD cells in a dose-dependent manner. ZFP91 upregulation was associated with significantly shorter survival of patients with PAAD. ZFP91 overexpression induced gemcitabine resistance, which was partly conquered by ginsenoside Rg3 treatment. ZFP91 depletion sensitized PANC-1/GR cells to gemcitabine treatment. ZFP91 interacted with Testis-Specific Y-Encoded-Like Protein 2 (TSPYL2), induced its poly-ubiquitination, and promoted proteasomal degradation. Ginsenoside Rg3 treatment weakened ZFP91-induced TSPYL2 poly-ubiquitination and degradation. Enforced TSPYL2 expression increased gemcitabine sensitivity of PAAD cells and partly reversed induced gemcitabine resistance in PANC-1/GR cells. Conclusion: Ginsenoside Rg3 can increase gemcitabine sensitivity of pancreatic adenocarcinoma at least via reducing ZFP91 mediated TSPYL2 destabilization.

RABL2A-CCDC34 Axis Promotes Sorafenib Resistance in Hepatocellular Carcinoma.

In this study, we examined the regulatory role of CCDC34 in the sorafenib sensitivity of hepatocellular carcinoma (HCC) and its functional partners. Wide-type Huh7 and Hep3B and induced sorafenib-resistant (SR) Huh7/SR and Hep3B/SR cells were used as in vitro cell models. Immunofluorescent staining and coimmunoprecipitation were performed to check protein-protein interaction. Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL), PI/Annexin V staining, and western blot analysis were performed to assess cell response to sorafenib. The results showed that CCDC34 upregulation in HCC was associated with poor survival. Huh7/SR and Hep3B/SR cells had significantly higher CCDC34 expression than the parental cell lines. RABL2A expression was significantly upregulated in SR HCC cells and interacted with CCDC34 in its GTP-bound state in Huh7/SR and Hep3B/SR cells. RABL2A depletion sensitized Huh7/SR and Hep3B/SR cells to sorafenib. RABL2A Q80L mutant (GTP-bound state locked), but not S35N mutant (GDP-bound state locked) overexpression increased sorafenib IC50 of Huh7 and Hep3B cells. CCDC34 depletion nearly abrogated the protective effects of RABL2A Q80L overexpression both in vitro and in vivo. RABL2A Q80L overexpression significantly increased the expression of p-p38 and p-JNK, the effects of which were significantly attenuated by CCDC34 depletion. In summary, we infer that the RABL2A-CCDC34 axis plays an important role in mediating p38/MAPK and JNK/MAPK signaling, thereby contributing to acquired sorafenib resistance in HCC.

POLE and Mismatch Repair Status, Checkpoint Proteins and Tumor-Infiltrating Lymphocytes in Combination, and Tumor Differentiation: Identify Endometrial Cancers for Immunotherapy.

OBJECTIVE: Although Polymerase-epsilon (POLE)-mutated and mismatch repair (MMR)-deficient endometrial cancers (ECs) are considered as promising candidates for anti-PD-1/PD-L1 therapy, selecting only these patients may exclude other patients who could potentially respond to this treatment strategy, highlighting the need of additional biomarkers for better patient selection. This study aims to evaluate potential predictive biomarkers for anti-PD-1/PD-L1 therapy in addition to POLE mutation (POLEm) and MMR deficiency (MMRd). METHODS: We performed next generation sequencing for POLE from 202 ECs, and immunohistochemistry for MLH1, MSH2, MSH6, PMS2, CD3, CD8, PD-1 and PD-L1 on full-section slides from these ECs. We assessed the association of POLEm and MMRd with clinicopathologic features, expression of check point proteins, and density of tumor-infiltrating lymphocytes (TILs). Prognostic impact of these immune markers was also evaluated. RESULTS: POLEm, MMRd and high-grade tumors exhibited elevated level of TILs. Increased expression of PD-1 and PD-L1 was observed in MMRd and high-grade ECs. A subgroup of MMR proficient ECs also harbored increased density of TILs, and positive expression of PD-1 and PD-L1. In addition, negative expression of checkpoint proteins and high density of TILs in combination was associated with good prognosis. CONCLUSIONS: Candidates for PD-1 blockade may extend beyond POLEm and MMRd ECs, additional factors such as tumor grade, and combination of TILs levels and expression of checkpoint proteins may need to be considered for better patient selection.

PLA2G16 is a mutant p53/KLF5 transcriptional target and promotes glycolysis of pancreatic cancer.

PLA2G16 is a member of the phospholipase family that catalyses the generation of lysophosphatidic acids (LPAs) and free fatty acids (FFAs) from phosphatidic acid. In the current study, we explored the functional role of PLA2G16 in pancreatic adenocarcinoma (PAAD) and the genetic/epigenetic alterations leading to its dysregulation. Bioinformatic analysis was performed using data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and the Human Protein Atlas (HPA). Then, PANC-1 and MIA-PaCa-2 cells harbouring TP53 mutations were used for cellular and animal studies. Results showed that PL2G16 expression was significantly up-regulated in PAAD tissue and was associated with unfavourable survival. PLA2G16 inhibition suppressed pancreatic cell growth in vitro and in vivo and also inhibited aerobic glycolysis. Bioinformatic analysis indicated that KLF5 was positively correlated with PLA2G16 expression in PAAD tumours with TP53 mutation. TP53 or KLF5 inhibition significantly reduced PLA2G16 expression at both mRNA and protein levels. Dual-luciferase and chromatin Immunoprecipitation-quantitative polymerase chain reaction assays showed that KLF5 directly bound to the PLA2G16 promoter and activated its transcription. Co-immunoprecipitation assay indicated that mutant p53 had a physical interaction with KLF5. Inhibition of mutant p53 impaired the transcriptional activating effects of KLF5. In PAAD cases in TCGA, PLA2G16 expression was positively correlated with its copy number (Pearson's r = 0.51, P < 0.001), but was strongly and negatively correlated with the methylation level of cg09518969 (Pearson's r = -0.64, P < 0.001), a 5'-cytosine-phosphodiester bond-guanine-3' site within its gene locus. In conclusion, this study revealed a novel mutant p53/KLF5-PLA2G16 regulatory axis on tumour growth and glycolysis in PAAD.

Management of medically inoperable and tyrosine kinase inhibitor-naïve early-stage lung adenocarcinoma with epidermal growth factor receptor mutations: a retrospective multi-institutional analysis.

BACKGROUND: The clinical value of combined local radiation and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for medically inoperable and TKI-naïve early-stage lung adenocarcinoma patients with EGFR mutations has not yet been determined. In this study, we aimed to pool multi-institutional data to compare the therapeutic effect of EGFR-TKI treatment alone and combined radiation and TKI treatment on the survival outcomes in this patient subgroup. METHODS: A total of 132 cases of medically inoperable stage I to III EGFR mutant lung adenocarcinoma were retrospectively reviewed based on data from 5 centers. Among these patients, 65 received combined radiation and EGFR-TKI therapy (R + TKI) (49.2%), while 67 received EGFR-TKI (50.8%) treatment alone. All patients were followed until death. RESULTS: For the R + TKI group, the median overall survival (OS) after primary therapy was 42.6 months, while that of the TKI alone group was 29.4 months (log-rank p < 0.001). In terms of progression-free survival (PFS), the median PFS in these two treatment groups was 24 months and 14.7 months respectively (log-rank p < 0.001). Multivariate analysis showed that R + TKI was independently associated with improved OS (adjusted HR 0.420; 95% CI 0.287 to 0.614; p < 0.001) and PFS (adjusted HR 0.420; 95% CI 0.291 to 0.605; p < 0.001) compared to TKI alone. Subgroup analysis confirmed the significant OS benefits in stage III patients and RFS benefits in stage II/III patients. CONCLUSIONS: Upfront radiation to primary sites with subsequent TKI treatment is a feasible option for patients with medically inoperable EGFR-mutant non-small-cell lung carcinoma (NSCLC) during first-line EGFR-TKI treatment, with significantly improved PFS and OS compared with those yielded by TKI treatment alone.

PLA2G4A Is a Potential Biomarker Predicting Shorter Overall Survival in Patients with Non-M3/NPM1 Wildtype Acute Myeloid Leukemia.

In this study, we aimed at exploring and validating the prognostic value of PLA2G4A expression in patients with non-M3/nucleophosmin (NPM1) wildtype (WT) acute myeloid leukemia (AML) by using two independent datasets. Data from the Cancer Genome Atlas-acute myeloid leukemia (TCGA-LAML) and the therapeutically applicable research to generate effective treatments (TARGET)-AML were used to assess the prognostic value of PLA2G4A in NPM1-WT AML cases. Results showed that non-M3 AML cases had significantly increased PLA2G4A expression compared with normal peripheral blood samples. Patients with high PLA2G4A expression (separated by median gene expression) had a significantly shorter overall survival (OS) compared with the group with low PLA2G4A expression, in both TCGA-LAML and TARGET-AML. Multivariate analysis showed that high PLA2G4A expression was independently associated with shorter OS in 97 non-M3/NPM1-WT AML cases in TCGA-LAML (hazard ratio [HR]: 1.946, 95% confidence interval [CI]: 1.094-3.462, q = 0.036). The prognostic value was validated based on 120 primary non-M3/NPM1-WT AML cases in TARGET-AML (HR: 1.518, 95% CI: 1.037-2.223, q = 0.048). Therefore, PLA2G4A expression might serve as an independent prognostic marker in OS in patients with non-M3/NPM1 WT AML. Bioinformatic analysis identified that several proteins physically interacted with PLA2G4A, some of which have well-characterized oncogenic properties in AML, such as RUVBL2, cytoskeleton regulatory protein 1 (CAP1), signal transducer and activator of transcription 3 (STAT3), and MYCBP. Therefore, we hypothesized that PLA2G4A upregulation has multiple effects on the malignant phenotype of AML cells together with its partners. Future molecular studies are required to explore the detailed regulatory network involved.

Long Noncoding RNA PTTG3P Expression Is an Unfavorable Prognostic Marker for Patients With Hepatocellular Carcinoma.

OBJECTIVE: PTTG3P, which maps to chromosome 8q13.1, is a novel long noncoding RNA with oncogenic properties in cancers. In this study, we aimed to investigate the prognostic value of PTTG3P in terms of overall survival and recurrence-free survival and its potential regulatory network and transcription pattern in patients with hepatocellular carcinoma. PATIENTS AND METHODS: An in silico analysis was performed using data from the Cancer Genome Atlas-Liver Hepatocellular Carcinoma. RESULTS: Results showed that the high PTTG3P expression group was consistently associated with shorter overall survival and recurrence-free survival, regardless of pathological stages or tumor grade. High PTTG3P expression was an independent indicator of shorter overall survival (hazard ratio: 2.177, 95% confidence interval: 1.519-3.121, P < .001) and recurrence-free survival (hazard ratio: 2.222, 95% confidence interval: 1.503-3.283, P < .001). The genes strongly coexpressed with PTTG3P are enriched in several KEGG pathways that are closely associated with carcinogenesis and malignant transformation of hepatocellular carcinoma. CONCLUSION: Based on the findings, we infer that PTTG3P expression might serve as an independent prognostic biomarker in primary hepatocellular carcinoma.

Correlation between TAMs and proliferation and invasion of type I endometrial carcinoma.

OBJECTIVE: To explore the correlation between tumor-associated macrophages and the proliferation and invasion of type I endometrial carcinoma. METHODS: Immunohistochemistry was used to investigate the infiltration of macrophages in normal and different types of hyperplastic endometrial lesions. The proliferation and invasion ability of type I endometrial carcinoma cell line RL95-2 influenced by mononuclear macrophage cell line THP-1 (constructed M2 type macrophages) was detected by CCK8 and transwell technologies respectively. Transwell was used to evaluate the recruiting ability of RL95-2 on THP-1 cells. Otherwise, the western blot was also used to detect the expression of CyclinD1 and MMP-2 in RL95-2 with the influence of THP-1. RESULTS: Immunohistochemistry result showed a positive correlation between the number of infiltrating macrophages and the progression of endometrial hyperplasia. THP-1 recruited by RL95-2 could promote its proliferation and invasion and enhance the expression of the CyclinD1 and MMP-2 protein in a time dependent manner (P < 0.05). CONCLUSIONS: Increase of the number of infiltrating macrophages and its contribution to the tumor inflammatory microenvironment may result in the development of the type I endometrial carcinoma.

The effect of radiofrequency ablation vs. liver resection on survival outcome of colorectal liver metastases (CRLM): a meta-analysis.

BACKGROUND/AIMS: For patients with solitary colorectal liver metastasis (CRLM), it is still controversial whether radiofrequency ablation (RFA) has the same effect as liver resection (LR). This study aims to pool available evidence and to analyze the effect of RFA versus LR for resectable solitary CRLM in sur- vival indicators. METHODOLOGY: Relevant studies were searched among databases and a meta-analysis was performed to pool the hazard ratio (HR) of RFA versus LR in overall survival (OS) and disease free survival (DFS). RESULTS: A total of 10 studies were included in this meta-analysis. Pooled results showed poorer OS (HR: 1.85, 95% CI: 1.48 to 2.32, p < 0.00001) and DFS (HR: 1.68, 95% CI: 1.14 to 2.48, p = 0.009) among the patient received RFA compared those received LR. Sensitivity analysis confirmed high robustness of the findings. CONCLUSION: In patients with resectable CRLM, LR is superior to RFA in survival outcomes. RFA should be reserved for patients who are not optimal candidates for resection until new supportive evidence is obtained from large RCTs.

rs11671784 G/A variation in miR-27a decreases chemo-sensitivity of bladder cancer by decreasing miR-27a and increasing the target RUNX-1 expression.

Single nucleotide polymorphism (SNP) rs11671784 is in the loop of pre-miR-27a and the G/A variation can significantly decrease mature miR-27a expression. This study explored the role of miR-27a in chemo-sensitivity of bladder cancer and how rs11671784 G/A variation affects the sensitivity. Blood and tumor samples from 89 bladder cancer cases were analyzed. In-vitro study was performed to explore the mechanism of chemo-sensitivity and the downstream target of miR-27a by using bladder cancer cell lines. This study identified a causative relationship between rs11671784 G/A variation, lowered miR-27a expression, increased RUNX-1 expression and following weakened chemo-sensitivity. rs11671784 G allele has significantly stronger effect over A allele in promoting chemo-sensitivity in bladder cancer. miR-27a mediates chemotherapy at least partially through reducing P-gp expression and increasing apoptosis. In addition, RUNX-1 is a novel direct target of miR-27a, which is involved in its regulation of chemo-sensitivity in bladder cancer.