Landscape of associations between long non-coding RNAs and infiltrating immune cells in liver hepatocellular carcinoma.

Liver hepatocellular carcinoma (LIHC) can be detected by the immune system; however, it acquires features for evasion of immune surveillance during its origin and development. Long non-coding RNAs (lncRNAs) are critical as immune regulators in cancers; nevertheless, the biological functions and mechanisms of lncRNAs in evasion of immune system by LIHC remain unclear. In this study, an integrated and computational approach was developed to identify immune-related lncRNAs and to divide LIHC patients into diverse immune-related risk groups based on the expression profiles of coding genes and lncRNAs. LIHC-specific genes and lncRNAs in 17 immune cell populations were identified and analysed. Gene and lncRNA co-expressing networks for diverse immune cell populations were constructed and analysed. Some imported immune-related lncRNAs, such as MIR9-3HG, were also identified. The LIHC patients comprised three different groups based on immune-related risk. LIHC patients possessing a greater diversity of immune cell populations had better survival prognosis. The collective data are evidence of a credible computational model that can prioritize novel immune-related lncRNAs and depict the atlas of immune-related lncRNAs in LIHC. These findings will further the understanding of lncRNA function and advance the identification of immunotherapy targets in LIHC.

Polygala tenuifolia polysaccharide PTP induced apoptosis in ovarian cancer cells via a mitochondrial pathway.

One purified polysaccharide protein tyrosine phosphatase (PTP) was isolated from the roots of Polygala tenuifolia. The aim of the present study is to investigate the antitumor effect of PTP on human ovarian cancer OVCAR-3 cells and explore the molecular mechanism of the action involved. The results of MTT assay and apoptosis detection assay showed that PTP inhibited cellular proliferation of OVCAR-3 cells and induced apoptotic cellular death via arresting cell circle at the G0/G1 phase. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis identified that bcl-2 gradually decreased at both transcription and protein levels after PTP treatment for 48 h in OVCAR-3 cells, while those of bax, cytochrome c, caspase-3, and caspase-9 increased. In addition, the low expression of NF-κB in PTP-treated OVCAR-3 cells would trigger the extrinsic pathway of programmed cell death signaling in tumor cells. These results together suggest that PTP may induce apoptosis of OVCAR-3 cells through a mitochondrial pathway.

Polygala tenuifolia polysaccharide (PTP) inhibits cell proliferation by repressing Bmi-1 expression and downregulating telomerase activity.

In our previous study, we isolated a homogeneous polysaccharide (PTP) with antitumor activity from the roots of Polygala tenuifolia. In view of the close correlation between Bmi-1 expression and progression of ovarian cancer, we intend to elucidate the mechanism of its activity by determining the Bmi-1 expression and the telomerase activity in human ovarian carcinoma OVCAR-3 cells following treatment with PTP at three concentrations of 0.5, 1, and 2 mg/mL for 48 h. MTT and colony-forming assays revealed that PTP had a significant inhibitory effect on the cell growth and colony formation of OVCAR-3 cells. Furthermore, Western blot and real-time PCR analysis showed that PTP inhibited Bmi-1 both in protein and transcript levels. Besides, the telomerase activity in OVCAR-3 cells was also downregulated after PTP treatment for 48 h. Taken together, the inhibitory effect of PTP on the cell growth was at least in part mediated via the downregulation of Bmi-1 expression and the telomerase activity in OVCAR-3 cells, and PTP might be a new candidate for chemotherapeutic agent against human ovarian cancer.

Peripheral T-cell subsets in radiofrequency ablation for tumors from different origins.

BACKGROUNDS: Radiofrequency ablation (RFA) is known to destroy tumoral tissue and activate immune cells. This study aimed to investigate the impact of RFA on peripheral T-cell responses and its relationship with tumor origin and hepatitis status. METHODS: A retrospective analysis was conducted on 62 patients with various types of tumors, including hepatocellular carcinoma, colorectal cancer, lung cancer, breast cancer, and others, who underwent RFA treatment between June 2017 and December 2018. Blood samples were collected before and one day after RFA treatment. The peripheral T-cell subsets were measured by flow cytometry, and their changes were analyzed. RESULTS: The study found a decrease in the CD4+CD8-and CD4-CD8+ T-cell subsets after RFA, but no significant changes were observed in the populations of CD4+CD8+ and the CD4+CD8-/CD4-CD8+ ratio. Furthermore, no significant differences were observed in peripheral T-cell subsets concerning tumor type or hepatitis status. CONCLUSIONS: The study suggests that RFA treatment may have a short-term impact on peripheral T-cell responses, characterized by a decrease in certain T-cell subsets. However, these changes do not seem to be related to the tumor type or hepatitis status of the patients.

Elevated expression of hyaluronic acid binding protein 1 (HABP1)/P32/C1QBP is a novel indicator for lymph node and peritoneal metastasis of epithelial ovarian cancer patients.

The present study aims to clarify whether hyaluronan binding protein 1 (HABP1/p32/C1QBP) is an indicator of peritoneal and lymph node metastasis in epithelial ovarian cancer (EOC), which to the authors' knowledge is not previously reported by others. Western blot analysis demonstrated that HABP1 was highly overexpressed in most metastatic lesions. Of 89 patients whose primary tumors showed high HABP1 expression on immunohistochemical staining, 85 (95.5%) presented peritoneal metastases and 43 (48.3%) had lymph node metastases. Univariate and multivariate logistic regression analyses revealed that HABP1 overexpression correlated with peritoneal dissemination and lymph node metastasis in EOC. The specificity and positive predictive value of HABP1 staining were shown to be better for peritoneal metastasis, while the negative and sensitivity predictive value of HABP1 staining were better for lymph node metastasis. The odds ratio of high versus low staining for peritoneal spread was 9.236 (95% confidence interval (CI), 2.705, 19.316), and that for lymph node metastasis was 8.614 (95% CI, 2.507, 21.039). Furthermore, HABP1 protein may potentially be used alone or in combination with other markers as a predictive marker of EOC patients with lymph node metastasis and/or peritoneal dissemination.

Identification of cuproptosis-related gene signature to predict prognosis in lung adenocarcinoma.

Background: Studies have reported that coppers are involved in the tumorigenesis and development of tumor. In herein, we aimed to construct a prognostic classification system for lung adenocarcinoma (LUAD) associated with cuproptosis. Methods: Samples information of LUAD were acquired from The Cancer Genome Atlas (TCGA) and GSE31210 dataset. Cuproptosis-related genes were screened from previous research. ConsensusClusterPlus was applied to determine molecular subtypes, which evaluated by genome analysis, tumor immune microenvironment analysis, immunotherapy, functional enrichment analysis. Furthermore, univariate Cox analysis combined with Lasso analysis were employed to construct a cuproptosis-related risk model for LUAD. Results: 14 genes related to cuproptosis phenotype were identified, and 2 clusters (C1 and C2) were determined. Among which, C1 had better survival outcome, less advanced stages, enhanced immune infiltration and enriched in TCA related pathways. A 7 cuproptosis-associated genes risk model was constructed, and the performance was verified in the GSE31210 dataset. A higher RiskScore was significantly correlated with worse overall survival, advanced stages. Cox survival analysis showed that RiskScore was an independent predictor. High-risk group patients had weakened immune infiltration, less likely to benefit from immunotherapy and was more sensitived to immunotherapy. Conclusion: The cuproptosis-related gene signature could serve as potential prognostic predictors for LUAD patients and may provide clues for the intervention of cuproptosis induced harm and targeted anti-tumor application.

Efficacy and Safety of Intrathecal Pemetrexed Combined With Dexamethasone for Treating Tyrosine Kinase Inhibitor-Failed Leptomeningeal Metastases From EGFR-Mutant NSCLC-a Prospective, Open-Label, Single-Arm Phase 1/2 Clinical Trial (Unique Identifier: ChiCTR1800016615).

INTRODUCTION: We aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating EGFR-mutant leptomeningeal metastases (LMs) from EGFR-mutant NSCLC. METHODS: Patients with EGFR-mutant NSCLC with LM who had failed tyrosine kinase inhibitors were recruited. The dose of IP was escalated from 15 mg to 80 mg using an accelerated titration design in a phase 1 study. The recommended dose (RD) determined in phase 1 was used in the phase 2 study. The primary end point was treatment efficacy measured as the clinical response rate. Overall survival and adverse events (AEs) were evaluated as secondary end points. RESULTS: The RD observed in the phase 1 study was 50 mg pemetrexed. A total of 30 cases of LM-NSCLC were enrolled in the phase 2 study, including 14 males and 16 females. Four patients did not survive for 4 weeks and could not be evaluated for efficacy. The clinical response rate was 84.6% (22 of 26). The median overall survival of all patients was 9.0 months (n = 30, 95% confidence interval: 6.6-11.4 mo). Most AEs were mild, and the most frequent AE of any grade was myelosuppression (n = 9, 30%), which returned to normal after symptomatic treatment. CONCLUSIONS: This study revealed that 50 mg pemetrexed is the RD which results in few AEs and a good response rate. IP is an effective treatment for patients with EGFR-mutant NSCLC-LM who had failed on tyrosine kinase inhibitor.

Elevation in the Expression of circ_0079586 Predicts Poor Prognosis and Accelerates Progression in Glioma via Interactions with the miR-183-5p/MDM4 Signaling Pathway.

PURPOSE: Glioma (GM) usually presents with an aggressive behavior and has a poor survival outcome. The abnormal expression of circular RNAs (circRNAs) has already been detected in GM, and circ_0079586 was found to have an increased expression in GM tumors. PATIENTS AND METHODS: We assessed the differences in the expression of circ_0079586 in GM tissues (N=60) and cell lines (N=5) using qRT-PCR. The clinical value of circ_0079586 was measured by Fisher's exact test and Kaplan-Meier and Cox regression analyses. Circ_0079586 siRNA and vector were transfected into LN229 and U251 cells, respectively, and the transfection was verified by qRT-PCR. Cell growth was evaluated by cell counting kit-8 (CCK-8). Cell apoptosis was measured using flow cytometric assay. Cell metastatic properties were measured by wound scratch and transwell experiments. Subcellular fractionation was used to identify the location of circ_0079586. Dual-luciferase reporter test was utilized to confirm the interaction between miR-183-5p and circ_0079586/MDM4 3'-UTR. RESULTS: The expression of circ_0079586 was elevated in GM samples and cells and correlated with the clinical severity and unfavorable prognosis of the patients. The elevated expression of circ_0079586 led to an increase in cell growth, migration and invasion but inhibited apoptosis in U251 cells, whereas its down-regulation reversed these effects in the LN229 cells. Mechanistically, we found circ_0079586 to be primarily located in the cytoplasm of GM cells. Furthermore, circ_0079586 could act as a sponge for miR-183-5p and elevate MDM4 expression at the posttranscriptional level. CONCLUSION: In summary, circ_0079586 was found to be up-regulated in GM that increased the proliferation, migration and invasion in GM cells via interaction with the miR-183-5p/MDM4 axis. We anticipate that our study would provide newer insights into the mechanism and treatment of GM.

The correlation of ESCO1 expression with a prognosis of prostate cancer and anti-tumor effect of ESCO1 silencing.

BACKGROUND: Recently, it has been reported that establishment of sister chromatid cohesion N-acetyltransferase 1 (ESCO1) is involved in tumorigenesis. However, its role in prostate cancer remains unclear. In the present study, the association between ESCO1 expression and the prognosis of prostate cancer was investigated, and the potential molecular mechanisms underlying its actions in tumor progression were also examined. METHODS: Immunohistochemical analysis was performed to detect the expression of ESCO1 in benign prostatic hyperplasia (BPH), human prostate cancer, and metastasis tissue samples, and the association between the establishment of ESCO1 expression and the prognosis of prostate cancer was investigated. The effect of ESCO1 expression on the viability, migration, and invasion of prostate cancer cells in vitro was analyzed, along with the effect of ESCO1 silencing on the growth of prostate tumors in vivo. RESULTS: The results demonstrated an increase in the expression of ESCO1 in prostate cancer tissue when compared with BPH, and it was significantly associated with tumor malignancy and poor patient survival. Additionally, knockdown of ESCO1 significantly inhibited the viability and migration of prostate cancer cell. Furthermore, we found that knockdown of ESCO1 significantly inhibited tumor growth in vivo. Pathway analysis identified that the silencing of ESCO1 significantly decreased the phosphorylation levels of protein kinase B. CONCLUSIONS: The results of the present study indicate that ESCO1 plays a vital role in the progression of human prostate cancer; furthermore, ESCO1 may potentially serve as a prognostic marker and a novel therapeutic target for this disease.

Comparison of efficacy and toxicity of bevacizumab, endostar and apatinib in transgenic and human lung cancer xenograftzebrafish model.

The poor prognosis in non-small-cell lung cancer has driven the development of novel targeted therapies. Vascular endothelial growth factor is the most potent force in mediating tumor angiogenesis, and many angiogenesis inhibitors have been developed for oncology treatment. We performed a study to characterize the efficacy, safety and tumor suppression of three lung cancer related anti-angiogenic drugs (bevacizumab, endostar and apatinib) using transgenic zebrafish embryo and human lung cancer xenotransplantation model. All three drugs demonstrated remarkable angiogenesis and tumor inhibition effect in the zebrafish model, within the nonlethal dose range. Endostar and bevacizumab showed competitive anti-tumor efficacy. The anti-tumor performance of apatinib was hamstrung by its elevated toxicity at 35 °C. The addition of pemetrexed to anti-angiogenesis therapy had no obvious additional benefit in tumors.

Pleural synovial sarcoma patient treated with combined chemotherapy and Endostar, plus sunitinib maintenance therapy: A case report and review of the literature.

Synovial sarcoma is a rare, highly malignant soft-tissue tumor that occurs primarily in the extremities. At present, there is no effective clinical treatment for this condition. The present study reports the case of a 49-year-old male who was diagnosed with pleural synovial sarcoma and treated with recombinant human endostatin (Endostar) combined with chemotherapy for a total of six cycles, followed by sunitinib maintenance therapy. To the best of our knowledge, this is the first reported use of sunitinib for maintenance therapy in pleural synovial sarcoma. The patient survived for 25 months after the recurrence of the disease following surgery. The results indicate that this combination therapy was effective in the treatment of pleural synovial sarcoma. The present study also briefly reviews the literature on pleural synovial sarcoma, and the features and treatments for this rare case are discussed.

Prognosis in very young women with triple-negative breast cancer: retrospective study of 216 cases.

The aim of this investigation was to compare clinical pathological characteristics and prognosis of very young and older triple-negative breast cancer (TNBC) patients in order to assess their relevance to TNBC in an younger population. Data of TNBC patients diagnosed between 2002 and 2007 were retrospectively analyzed by computer based chart information. Baseline tumor characteristics, biological markers, and patients' prognosis were compared between very young (≤ 35 years) and older (>35 years) TNBC patients. In the 216 cases of operable TNBC patients, 48 (22.2%) were ≤ 35 years and 168 (77.8%) were >35 years. Very young TNBC patients had showed a high clinical stage, more positive lymph nodes, Ck5/6 and/or EGFR expression (P = 0.049, 0.006, and 0.011, respectively). Compared to older TNBC patients, very young TNBC patients have short disease-free survival (P = 0.031), while no significant difference was found in overall survival (OS) (P = 0.075). In multivariate analysis, lymph node metastatic status was a significant predictor of OS. TNBC of very young patients is an aggressive breast cancer subtype, but the overall survival of both young and older TNBC patients did not have significant differences.

CD147, MMP9 expression and clinical significance of basal-like breast cancer.

Our objective is to investigate the expression of CD147 and metallo-proteinase 9 (MMP9) in patients with basal-like breast cancer (BLBC) so as to determine whether these two genes may be correlated with prognosis of BLBC. We examined the expression of the CD147 and MMP9 in BLBC by immunohistochemistry. Furthermore, we analyzed the correlation between BLBC and several factors related to tumor progression, along with the prognostic value of BLBC. BLBC was significantly associated with CD147 and MMP9 expression (P = 0.000), and prone to lymph node metastasis and distant metastasis. Patients with BLBC showed shorter disease-free survival (P = 0.005) and overall survival (OS) (P = 0.011). In univariate analysis, CD147, MMP9, lymph node metastasis and clinical stage are independent prognostic factors affecting OS. In multivariate analysis, only clinical stage was identified as an independent prognostic factor. Patients with BLBC have a high expression of CD147 and MMP9; BLBC is correlated with a poor prognosis.

Purification and antitumor activity of two acidic polysaccharides from the roots of Polygala tenuifolia.

Two acidic polysaccharide fractions (PTPa and PTPb) extracted from the roots of Polygala tenuifolia, were obtained by DEAE-Sephacel anion-exchange, and Sephadex G-100 gel-permeation chromatography. High-performance liquid chromatography (HPLC) identified that PTPa and PTPb was composed of Ara, Glc, Gal, Man and GlcUA in the proportion of 2.4:1.2:0.6:0.4:1.1 and 2.1:1.7:0.5:0.6:1.7, respectively. Their molecular weight was evaluated to be 5.9×10(4) (PTPa) and 2.5×10(4) Da (PTPb) as determined by high performance size exclusion chromatography (HPSEC). Pharmacological studies revealed PTPa and PTPb significantly inhibited the growth of A549 cells in vitro and exhibited significantly higher antitumor activity against solid tumor A549 in vivo than did a blank control. Moreover, treatment with two acidic polysaccharides caused an enhancement of superoxide dismutase (SOD) and catalase (CAT) activities in tumor-bearing mice and a reduction in thiobarbituric acid reactive substances (TBARS) level. Taken together, these results indicated that two acidic polysaccharides from the roots of P. tenuifolia may be useful as potent antitumor agents for the prevention of lung tumorigenesis.