Identification of ZIC2 as a Potential Biomarker Linked with the Clinical Progression and Immune Infiltration of Oral Cancer: A Multicenter Study.

Aim: To investigate the specific expression profile, clinicopathological significance and mechanism of Zic family member 2 (ZIC2) in oral cancer were unclear. Patients and Methods. We explored the expression pattern and clinicopathological significance of ZIC2 in oral cancer through performing in-house tissue microarray and integrated analysis global RNA-seq and microarrays containing large samples. The molecular basis of ZIC2 in oral cancer was further investigated in the aspects of transcription network and immune correlations. We also performed in vitro experiments and calculated drug sensitivity of oral cancer with different ZIC2 expression levels in response to hundreds of compounds. Results: All data unanimously proved the significant overexpression of ZIC2 in oral cancer. The upregulation of ZIC2 was remarkably associated with the malignant clinical progression of oral cancer. ZIC2 was predicted to be targeted by miRNAs such as miR-3140, miR-4999, and miR-1322. The infiltration level of CD8+ T and central memory cells was positively related to the overexpression of ZIC2. Oral cancer patients with higher ZIC2 expression showed higher drug sensitivity to two compounds including AZD8186 and ERK_2240. Conclusions: We demonstrated the upregulation of ZIC2 in oral cancer and its promoting effect on the clinical advancement of oral cancer. The potential clinical value of ZIC2 in oral cancer deserves attention.

Prognostic Value of Lymph Node Necrosis at Different N Stages in Patients with Nasopharyngeal Carcinoma.

Background: Lymph node necrosis (LNN), including retropharyngeal nodal necrosis and cervical nodal necrosis, which is related to radiotherapy/ chemotherapy resistance, is a common phenomenon in nasopharyngeal carcinoma (NPC). This study was to assess the prognostic value of LNN at different N stages in NPC patients. Materials and Methods: In total, 1,665 newly diagnosed NPC patients at stage TxN1-3M0 from two centers were enrolled. Univariate and multivariate models were constructed to assess the association between LNN and long-term survival outcomes. The propensity score matching method was performed to balance treatment groups for baseline characteristics. Results: Of the 1,665, 540 patients (540/1665, 32.4%) were diagnosed with LNN, of which 54.1% (292/540) patients were at stage N1, 31.3% (169/540) at stage N2, and 14.6% (79/540) at stage N3. Univariate and multivariate analyses indicated LNN as an independent predictor for progression­free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) in stage N1-3 patients (all P<0.001). When patients were analyzed according to stage, similar findings were observed for N1 patients (all P<0.001); for N2 patients, LNN independently predicted PFS (P=0.003), OS (P=0.011), and DMFS (P=0.004), and for stage N3, LNN only independently predicted LRRFS (P=0.019). 123 pairs of patients who received induction chemotherapy plus concurrent chemoradiotherapy or only concurrent chemoradiotherapy were matched, adding induction chemotherapy improved 5-year OS, PFS and LRFFS, but the results were not statistically significant. Conclusions: In NPC patients, LNN could independently predict poor prognosis at all N1-3 stages and at each N stage (N1 to N3). The value of adding induction chemotherapy to concurrent chemoradiotherapy in patients with LNN still requires further prospective studies.

Role of Up-Regulated Transmembrane Channel-Like Protein 5 in Pancreatic Adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a malignant tumor responsible for a heavy disease burden. Previously, only one pan-cancer study of Transmembrane channel-like protein 5 (TMC5) showed that TMC5 was highly expressed in PAAD, but the results lacked comprehensive verification, and the mechanism of TMC5 in PAAD was still unclear. METHODS: For exploring the expression and clinical value of TMC5 in PAAD better, we adopted a comprehensive evaluation method, using internal immunohistochemistry (IHC) data combined with microarray and RNA-sequencing data collected from public databases. The single cell RNA-sequencing (scRNA-seq) data were exploited to explore the TMC5 expression in cell populations and intercellular communication. The potential mechanism of TMC5 in PAAD was analyzed from the aspects of immune infiltration, transcriptional regulation, function and pathway enrichment. RESULTS: Our IHC data includes 148 PAAD samples and 19 non-PAAD samples, along with the available microarray and RNA-sequencing data (1166 PAAD samples, 704 non-PAAD samples). The comprehensive evaluation results showed that TMC5 was evidently up-regulated in PAAD (SMD = 1.17). Further analysis showed that TMC5 was over-expressed in cancerous epithelial cells. Furthermore, TMC5 was up-regulated in more advanced tumor T and N stages. Interestingly, we found that STAT3 as an immune marker of Th17 cells was not only positively correlated with TMC5 and up-regulated in PAAD tissues, but also the major predicted TMC5 transcription regulator. Moreover, STAT3 was involved in cancer pathway of PAAD. CONCLUSION: Up-regulated TMC5 indicates advanced tumor stage in PAAD patients, and its role in promoting PAAD development may be regulated by STAT3.

A Multicenter Randomized Trial Assessing ZENFlow Carrier-Free Drug-Coated Balloon for the Treatment of Femoropopliteal Artery Lesions.

Backgrounds and Objectives: Drug-coated balloons (DCBs) have shown promising benefits in improving the outcomes for patients with peripheral artery disease. Several randomized clinical trials have reported that paclitaxel-coated balloon significantly reduce the rates of restenosis and the need for reintervention in comparison with regular balloon angioplasty. Due to the differences in excipients, paclitaxel dose, and coating techniques, variable clinical outcomes have been observed with different DCBs. In this study, we aimed to evaluate the safety and efficacy of a novel ZENFlow carrier-free DCB in the treatment of femoropopliteal artery occlusive disease. Methods: In this randomized controlled trial conducted at 15 sites, 192 patients with Rutherford class 3-5 were randomly assigned into two groups: drug-coated balloon group and percutaneous transluminal angioplasty group. The primary endpoint was a late lumen loss at 6 months based on blinded angiographic core laboratory evaluations, and the secondary endpoints included primary patency rate, binary restenosis, clinically driven target lesion revascularization, ankle-brachial index, Rutherford class change, and major adverse events. Results: In this multicenter trial, 93 patients received DCB angioplasty, whereas 99 patients underwent regular balloon angioplasty. The late lumen loss at 6-month follow-up was 0.50 ± 0.82 and 1.69 ± 0.87 mm in the drug-coated balloon and percutaneous transluminal angioplasty groups, respectively (p < 0.001). During the 12-month follow-up period, the drug-coated balloon group showed a significantly higher primary patency rate (54 vs. 31.3%, p = 0.009) and markedly lower rates of target vessel restenosis (22.1 vs. 64.3%, p < 0.001) and clinically driven target lesion revascularization rate (5.4 vs. 19.2%, p = 0.006) than the percutaneous transluminal angioplasty group. Compared with the percutaneous transluminal angioplasty group, the drug-coated balloon group had significant improvements in the ankle-brachial index and Rutherford class. The all-cause mortality rate was comparable, and no device-related deaths occurred in either groups. Conclusions: Balloon angioplasty using a ZENFlow carrier-free drug-coated balloon is a safe and effective treatment method for femoropopliteal artery lesions. This novel drug-coated balloon catheter achieved satisfactory early and 1-year outcomes in this trial. Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT03844724.

Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment.

Objective: Osteoporosis has become the biggest cause of non-fatal health issue. Currently, the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance, have raised concerns toward complementary and alternative therapies, particularly herbal medicines and their natural active compounds. Thus, this study aimed to provide an integrative analysis of active chemicals, drug targets and interacting pathways of the herbs for osteoporosis treatment. Methods: Here, we introduced a systematic pharmacology model, combining the absorption, distribution, metabolism, and excretion (ADME) screening model, drug targeting and network pharmacology, to probe into the therapeutic mechanisms of herbs in osteoporosis. Results: We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs. Network analysis revealed that they probably synergistically work through multiple mechanisms, such as suppressing inflammatory response, maintaining bone metabolism or improving organism immunity, to benefit patients with osteoporosis. Furthermore, experimental results showed that all the five compounds (calycosin, asperosaponin VI, hederagenin, betulinic acid and luteolin) enhanced osteoblast proliferation and differentiation in vitro, which corroborated the validity of this system pharmacology approach. Notably, gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis. Conclusion: Herbs and their natural compounds, being characterized as the classical combination therapies, might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms. This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.

Influence of tumor necrosis on treatment sensitivity and long-term survival in nasopharyngeal carcinoma.

PURPOSE: To assess the impact of tumor necrosis on treatment sensitivity and long-term survival in patients with nasopharyngeal carcinoma (NPC) treated using intensity-modulated radiation therapy (IMRT). PARTICIPANTS AND METHODS: In total, 757 patients with non-metastatic, histologically confirmed NPC were retrospectively examined. All patients were treated using IMRT; 93.7% patients with stage T3-T4/N1-N3 disease also received cisplatin-based chemotherapy. RESULTS: The incidence rates of tumor necrosis in primary tumor, retropharyngeal lymph nodes, neck lymph nodes, and total tumor were 2%, 17.7%, 21.5%, and 31.4%. Overall, 40.8% patients with necrosis of the total tumor achieved complete response (CR) and 54.7% patients without tumor necrosis achieved CR at the end of treatment (χ2 = 12.728, P < 0.001). The estimated 7-year overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS), and loco-regional relapse-free survival (LRRFS) for patients with tumor necrosis and without tumor necrosis of the total tumor were 68.5% vs. 88.4%, 70.5% vs. 88.1%, 77.6% vs. 90.6%, and 85.9% vs. 91.3%, respectively (all P < 0.001). Multivariate analyses indicated that necrosis of the total tumor was an independent predictor of OS, FFS, DMFS, and LRRFS. The impact of lymph node necrosis on long-term survival was similar to that of necrosis of the total tumor. ROC curves verified that inclusion of lymph node necrosis improved the predictive value of the current N classification criteria (P = 0.006). CONCLUSIONS: Tumor necrosis served as a predictor of treatment sensitivity and poor prognosis for patients with NPC. Lymph node necrosis significantly improved the prognostic value of the current N classification criteria for NPC.

Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment / 中草药·英文版

Objective: Osteoporosis has become the biggest cause of non-fatal health issue. Currently, the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance, have raised concerns toward complementary and alternative therapies, particularly herbal medicines and their natural active compounds. Thus, this study aimed to provide an integrative analysis of active chemicals, drug targets and interacting pathways of the herbs for osteoporosis treatment. Methods: Here, we introduced a systematic pharmacology model, combining the absorption, distribution, metabolism, and excretion (ADME) screening model, drug targeting and network pharmacology, to probe into the therapeutic mechanisms of herbs in osteoporosis. Results: We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs. Network analysis revealed that they probably synergistically work through multiple mechanisms, such as suppressing inflammatory response, maintaining bone metabolism or improving organism immunity, to benefit patients with osteoporosis. Furthermore, experimental results showed that all the five compounds (calycosin, asperosaponin VI, hederagenin, betulinic acid and luteolin) enhanced osteoblast proliferation and differentiation in vitro, which corroborated the validity of this system pharmacology approach. Notably, gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis. Conclusion: Herbs and their natural compounds, being characterized as the classical combination therapies, might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms. This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.

Dark tea extracts: Chemical constituents and modulatory effect on gastrointestinal function.

Processing of dark tea varieties, such as Fu brick tea, Liupao tea, Qianliang tea, and Qing brick tea, includes solid-state fermentation involving microorganisms. In this study, we analyzed the major chemical constituents of dark tea extracts and evaluated their modulatory effect on the gastrointestinal function in normal mice, including the improvement of gastrointestinal transit and intestinal microbial, as well as the attenuation of intestinal microbial dysbiosis and intestinal pathological damage, and the adjustment of immune function in antibiotic-treated mice. Substantial differences in major chemical constituents, including total polyphenols, total organic acids, water extract content, 18 free amino acids, gallic acid, and six tea catechins, were observed among Fu brick tea, Qianliang tea, Qing brick tea, and Liupao tea extracts. Extracts from the four dark tea varieties significantly promoted gastrointestinal transit and colonization of beneficial Bifidobacterium and Lactobacillus, and inhibited the growth of harmful Escherichia coli and Enterococcus in normal mice. In addition, Qianliang tea, Qing brick tea, and Liupao tea extracts significantly accelerated the reversal of the ampicillin sodium-induced pathological damage in the ileum, intestinal bacterial dysbiosis (Bifidobacterium, Lactobacillus, E. coli, and Enterococcus), and low immunity.

Clinicopathological value and underlying molecular mechanism of annexin A2 in 992 cases of thyroid carcinoma.

BACKGROUND: Thyroid carcinoma (THCA) is one of the most frequent endocrine cancers and has increasing morbidity. Annexin A2 (ANXA2) has been found to be highly expressed in various cancers; however, its expression level and potential mechanism in THCA remain unknown. This study investigated the clinicopathological value and primary molecular machinery of ANXA2 in THCA. MATERIAL AND METHODS: Public RNA-sequencing and microarray data were obtained and analyzed with ANXA2 expression in THCA and corresponding non-cancerous thyroid tissue. A Pearson correlation coefficient calculation was used for the acquisition of ANXA2 coexpressed genes, while edgR, limma, and Robust Rank Aggregation were employed for differentially expressed gene (DEG) in THCA. The probable mechanism of ANXA2 in THCA was predicted by gene ontology and pathway enrichment. A dual-luciferase reporter assay was employed to confirm the targeting relationships between ANXA2 and its predicted microRNA (miRNA). RESULTS: Expression of ANXA2 was significantly upregulated in THCA tissues with a summarized standardized mean difference of 1.09 (P < 0.0001) based on 992 THCA cases and 589 cases of normal thyroid tissue. Expression of ANXA2 was related to pathologic stage. Subsequently, 1442 genes were obtained when overlapping 4542 ANXA2 coexpressed genes with 2248 DEGs in THCA; these genes were mostly enriched in pathways of extracellular matrix-receptor interaction, cell adhesion molecules, and complement and coagulation cascades. MiR-23b-3p was confirmed to target ANXA2 by dual-luciferase reporter assay. CONCLUSIONS: Upregulated expression of ANXA2 may promote the malignant biological behavior of THCA by affecting the involving pathways or being targeted by miR-23b-3p.

Identification of prognostic splicing factors and exploration of their potential regulatory mechanisms in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD), the most common subtype of pancreatic cancer, is a highly lethal disease. In this study, we integrated the expression profiles of splicing factors (SFs) of PAAD from RNA-sequencing data to provide a comprehensive view of the clinical significance of SFs. A prognostic index (PI) based on SFs was developed using the least absolute shrinkage and selection operator (LASSO) COX analysis. The PI exhibited excellent performance in predicting the status of overall survival of PAAD patients. We also used the percent spliced in (PSI) value obtained from SpliceSeq software to quantify different types of alternative splicing (AS). The prognostic value of AS events was explored using univariate COX and LASSO COX analyses; AS-based PIs were also proposed. The integration of prognosis-associated SFs and AS events suggested the potential regulatory mechanisms of splicing processes in PAAD. This study defined the markedly clinical significance of SFs and provided novel insight into their potential regulatory mechanisms.

A combined marker based on plasma D-dimer and serum albumin levels in patients with nasopharyngeal carcinoma is associated with poor survival outcomes in a retrospective cohort study.

Background: Activation of the clotting-fibrinolytic system in cancer patients is common and results in an unfavorable clinical outcome. This study aimed to investigate the role of pretreatment plasma D-dimer levels and the combination of D-dimer and albumin (DA) on the prediction of survival prognosis in patients with nasopharyngeal carcinoma (NPC). Methods: The study comprised 511 patients with NPC. Pretreatment plasma D-dimer and serum albumin levels were measured. DA was classified as a new biomarker where D-dimer and albumin levels were combined and was grouped by the cutoff value of both. The correlations of plasma D-dimer levels with clinicopathological features and survival outcome were calculated using the Chi-square test. Kaplan-Meier estimates were performed to analyze the survival functions and were compared using log-rank tests. Cox proportional hazard regression analysis was used to assess the effects of D-dimer and DA on distant overall survival (OS) and distant metastasis-free survival (DMFS). Results: The median follow-up period was 45.2 months (range 2.1-79.8). Elevated plasma D-dimer levels were positively associated with age at diagnosis (P = 0.034), platelet levels (P = 0.043), and Epstein Barr Virus (EBV) DNA copy number (P = 0.035). Additionally, multivariate analysis demonstrated that elevated plasma D-dimer levels were strongly associated with a poorer OS (HR 2.074, 95% CI 1.190-3.612, P = 0.010), but not DMFS. After adjustment for other variables, DA stratification acted as an independent prognostic marker for OS (P = 0.038) and DMFS (P = 0.031) in patients with NPC, when combined with albumin levels. Conclusions: Increased plasma D-dimer levels accurately predict poor OS and may be an effective independent prognostic factor in patients with NPC. Moreover, in conjunction with serum albumin, DA may serve as a factor in predicting OS and DMFS.

MiR-193a-3p inhibits pancreatic ductal adenocarcinoma cell proliferation by targeting CCND1.

Background: MicroRNAs (miRNAs) could modulate gene expression at the posttranscriptional level by promoting mRNA degradation or blocking mRNA translation, thus affecting the occurrence and development of cancer. Methods: In this work, qRT-PCR was conducted to detect the expression of miR-193a-3p and CCND1. The ability of cell proliferation was evaluated via CCK-8 assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Bioinformatic techniques were employed to research the regulatory relationship between miR-193a-3p and target genes. The relationship between miR-193a-3p and CCND1 was verified via dual-luciferase reporter assays. Results: MiR-193a-3p expression in pancreatic ductal adenocarcinoma (PDAC) tissue was significantly lower than in non-cancerous tissue. After overexpressing miR-193a-3p in PDAC cells, their multiplication ability was significantly inhibited, apoptosis was accelerated, and the cell cycle was blocked in the G1 and G2/M phases. CCND1 was confirmed to have a targeted relationship with miR-193a-3p. Moreover, CCND1 expression was significantly lower in PDAC cells with an overexpression of miR-193a-3p. Conclusions: MiR-193a-3p targeted CCND1 to suppress tumor growth in PDAC cells. MiR-193a-3p may function as a tumor inhibitor in PDAC development, which could offer a promising therapeutic and prognostic strategy for PDAC treatment.

Comparison between paclitaxel-coated balloon and standard uncoated balloon in the treatment of femoropopliteal long lesions in diabetics.

Atherosclerotic diseases may include femoropopliteal artery stenosis or occlusion. Percutaneous transluminal angioplasty (PTA) is an effective and minimally invasive treatment strategy for atherosclerotic femoropopliteal artery stenosis/occlusion disease. Balloon angioplasty is a widely used technique in the management of occlusive disease in almost all arterial segments.We enrolled 111 diabetics with long femoropopliteal lesions, among which 54 received PTA with paclitaxel-coated balloon (the Paclitaxel group), and 57 with standard balloon catheters (the Control group).The primary outcome was set as angiographic late lumen loss (LLL) within 6 months; the secondary angiographic outcome was binary restenosis. Clinical outcomes included Rutherford clarification, ankle-brachial index (ABI) and rate of clinically driven target lesion revascularization (TLR). Two groups had similar basal clinical features, angiographic and procedural characteristics. Compared to controls, the Paclitaxel group had a significantly lower 6-month LLL rate, 12-month binary restenosis rate, 12-month TLR, lower Rutherford grades at 3 and 6 months, and higher ABI at 3 months. For all factors which might influence outcomes, fasting blood glucose was negatively correlated with ABI; the blood urea nitrogen (BUN) was positively related with the Rutherford clarification grades. In addition, the coronary heart disease (CHD) and smoking histories were positively correlated with residual stenosis after treatment.Collectively, the paclitaxel-coated balloon angioplasty can yield more favorable angiographic and clinical outcomes than standard uncoated balloon angioplasty, even in the more challenging lesions (the long and occlusive femoropopliteal lesions) in diabetics, when it had a similar safety profile to the traditional balloon. Blood glucose, BUN, CHD, and smoking imply poor curative effects.

Metachronous Sigmoid Carcinoma and Mantle Cell Lymphoma in Intestines.

It is rare that colon carcinoma and mantle cell lymphoma (MCL) occur one after another in intestines. We found two malignancies of sigmoid carcinoma and MCL in a single patient, who had initially been diagnosed with sigmoid carcinoma and treated with radical resection in our hospital. Good postoperative recovery was reported without recurrence signs, which lasted for 7 years and 5 months until polyps of sigmoid colon were found by colonoscopy. Biopsy and immunohistochemistry revealed MCL, but the patient refused treatment. One year later, MCL was diagnosed again in the transverse colon. The patient is currently under observation and has not received treatment for MCL.

Prognostic value of gross tumor regression and plasma Epstein Barr Virus DNA levels at the end of intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma.

PURPOSE: To assess gross tumor regression and plasma Epstein-Barr virus (EBV)-DNA levels at the end of intensity-modulated radiation therapy (IMRT) and its prognostic impact on patients with nasopharyngeal carcinoma (NPC). PARTICIPANTS AND METHODS: In total, 397 patients with non-metastatic, histologically confirmed NPC were retrospectively examined. All patients underwent magnetic resonance imaging of the nasopharynx and neck, and plasma EBV DNA assays before treatment and at the end of IMRT. RESULTS: The estimated 5-year loco-regional, local and regional relapse-free survival rates for patients with complete response (CR) and non-CR of the total tumor, primary tumor and metastatic lymph nodes at the end of IMRT were 94.9% vs. 85.8%, 96.6% vs. 87.3%, and 98.7% vs. 89.8%, respectively (P < 0.05). The estimated 5-year loco-regional relapse-free survival (LRRFS) rates for patients with persistent tumor with and without boost irradiation were 95.3% vs. 83%, respectively (P = 0.034). The estimated 5-year overall survival (OS), failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates for patients with negative and positive plasma EBV DNA at the end of IMRT were 83.1% vs. 50.3%, 81.5% vs. 49.3%, and 87.6% vs. 61.5%, respectively (P < 0.001). Multivariate analyses indicated that regression of the total tumor and boost irradiation was an independent predictor of LRRFS, and plasma EBV DNA levels were independent predictors of OS, FFS and DMFS. CONCLUSIONS: Gross tumor regression and plasma EBV DNA levels at the end of IMRT served as predictors of poor prognosis for patients with NPC. The patients with persistent tumor and/or positive plasma EBV DNA might require timely strengthening treatment.

Potential ceRNA networks involved in autophagy suppression of pancreatic cancer caused by chloroquine diphosphate: A study based on differentially­expressed circRNAs, lncRNAs, miRNAs and mRNAs.

Autophagy has been reported to be involved in the occurrence and development of pancreatic cancer. However, the mechanism of autophagy­associated non­coding RNAs (ncRNAs) in pancreatic cancer remains largely unknown. In the present study, microarrays were used to detect differential expression of mRNAs, microRNAs (miRNAs), long ncRNAs (lncRNAs) and circular RNAs (circRNAs) post autophagy suppression by chloroquine diphosphate in PANC­1 cells. Collectively, 3,966 mRNAs, 3,184 lncRNAs and 9,420 circRNAs were differentially expressed. Additionally, only two miRNAs (hsa­miR­663a­5p and hsa­miR­154­3p) were underexpressed in the PANC­1 cells in the autophagy­suppression group. Furthermore, miR­663a­5p with 9 circRNAs, 8 lncRNAs and 46 genes could form a prospective ceRNA network associated with autophagy in pancreatic cancer cells. In addition, another ceRNA network containing miR­154­3p, 5 circRNAs, 2 lncRNAs and 11 genes was also constructed. The potential multiple ceRNA, miRNA and mRNA associations may serve pivotal roles in the autophagy of pancreatic cancer cells, which lays the theoretical foundation for subsequent investigations on pancreatic cancer.

Lorlatinib: a third generation ALK inhibitor for treatment of non-small cell lung carcinoma / 药学学报

Lorlatinib (PF-06463922) is a highly selective and potent third generation anaplastic lymphoma kinase (ALK) inhibitor with dual activity against c-ros oncogene 1, a receptor tyrosine kinase (ROS1). In November 2018, the US Food and Drug Administration approved lorlatinib for treatment of disease progression in ALK-positive and late-stage NSCLC patients who receive the treatment with crizotinib and at least one of other ALK inhibitors; and those with disease progression after treatment of alectinib or ceritinib as the first ALK inhibitor. The results of phase I/II clinical trials showed that it has effective initial anti-tumor activity, strong intracranial therapeutic activity, with less tolerance and safety issues. This paper systematically reviewed the chemical structure, mechanism of action, pharmacodynamics, pharmacokinetics, usage and dosage, clinical research, safety and upcoming research fields of lolatinib, to provide an update on clinical or laboratory research and clinical practice.

Biological Effect and Mechanism of the miR-23b-3p/ANXA2 Axis in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIMS: Accumulating evidence strongly suggests that microRNAs (miRNAs) modulate the expression of known tumor suppressor genes and oncogenes. In the present study, we found that the proliferation and invasion ability of pancreatic ductal adenocarcinoma (PDAC) cells were significantly suppressed by the overexpression of miR-23b-3p. In addition, there are miR-23b-3p binding sites in annexin A2 (ANXA2). Here, we investigated whether miR-23b-3p had an impact on the progression and metastasis of PDAC by targeting ANXA2. METHODS: Cell proliferation, migration, and invasion, and cell cycle assays were performed to explore the effect of miR-23b-3p on various malignant phenotypes of pancreatic cancer cells. The size of tumors was observed following miR-23b-3p overexpression in an in vivo chick chorioallantoic membrane assay. Dual-luciferase reporter, quantitative real-time PCR, western blot, and immunohistochemical analyses were used to validate the relationship between miR-23b-3p and ANXA2 in vitro. RESULTS: We observed that miR-23b-3p could bind specifically to the 3' untranslated region of ANXA2 and inhibit its expression. MiR-23b-3p overexpression downregulated the expression of ANXA2 mRNA in PDAC cells and limited the size of tumors or even prevented tumor formation. In addition, there was a negative correlation between miR-23b-3p expression and ANXA2 protein expression in clinical specimens. CONCLUSION: MiR-23b-3p inhibits the development and progression of PDAC by regulating ANXA2 directly.

Identification of Ethylene Responsive miRNAs and Their Targets from Newly Harvested Banana Fruits Using High-Throughput Sequencing.

The roles of microRNAs (miRNAs) related to ethylene response in banana fruits remain unknown because many miRNAs are differentially expressed as the fruit ripens, making the identification of ethylene-responsive miRNAs difficult. Using newly harvested banana fruits (within 5 h after harvest) as material, we found that these fruit did not ripen when treated with 5 µL/L of ethylene for 12 h at 22 °C. Two miRNA libraries were generated from newly harvested banana fruits with and without ethylene treatment and sequenced. In total, 128 known miRNAs belonging to 42 miRNA families were obtained, and 12 novel miRNAs were identified. Among them, 22 were differentially expressed in response to ethylene treatment, among which 6 known miRNAs and their putative targets were validated using qRT-PCR. These putative targets encoded proteins including GATA, ARF, DLC, and AGO, etc. KEGG and GO analyses showed that miRNAs differentially expressed in response to ethylene mainly function in the molecular and biological processes.

Additional Cervical Lymph Node Biopsy is Not a Significant Prognostic Factor for Nasopharyngeal Carcinoma in the Intensity-Modulated Radiation Therapy Era: A Propensity Score-matched Analysis from an Epidemic Area.

Introduction: This study aimed to evaluate the prognostic value of cervical lymph node biopsy and whether different biopsy methods would lead different outcomes in NPC in the intensity-modulated radiotherapy (IMRT) era. Material and Methods: 1492 patients with biopsy-proven, non-metastatic NPC, and treated by IMRT with or without chemotherapy were retrospectively reviewed. Cervical lymph node biopsy was performed in 183 (12.3%) patients: 61(4.1%) by needle puncture and 118(7.9%) by excision biopsy. Propensity-score matching was used to match patients in both arms at an equal ratio. Overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRFS), and nodal relapse-free survival (NRFS) were assessed using the Kaplan-Meier method and compared using the log-rank test. Independent prognostic factors were identified using the Cox proportional hazards model. Results: In the original cohort of 1492 patients, patients receiving cervical lymph node biopsy had comparable survival (OS: P = 0.736, DMFS: P = 0.749, LRFS: P = 0.538, NRFS: P = 0.093,) with patients receiving isolated napharynx biopsy. The results for the propensity-match cohort of 316 patients were similar. Interestingly, compared with the control group and needle puncture biopsy group, a slightly lower nodal recurrence rate was observed in the excision biopsy group (P = 0.082 and P = 0.072, respectively). Adjusting for the known prognostic factors in multivariate analysis, cervical biopsy did not cause a higher risk of death, distant metastasis, or nodal relapse. Conclusions: Pretreatment cervical lymph node biopsy is not associated with impaired survival in NPC, suggesting the resist of the biopsy and more aggressive treatment after the biopsy may be unnecessary.