Case report: Response to Savolitinib/EGFR-TKI combination in NSCLC patients harboring concurrent primary MET amplification/overexpression and EGFR mutation.

Lung cancer is the leading cause of cancer death, accounting for one-third of all cancer deaths worldwide. The MET (c-MET) gene, as one of the therapeutic target spots of NSCLC, has become increasingly more important. MET amplification/overexpression was divided into primary (intrinsic) and secondary (acquired). Studies indicated that the combination of Osimertinib and Savolitinib was safe and showed promising antitumor effect in NSCLC patients with secondary MET amplification after EGFR mutations. However, NSCLC patients with primary MET amplification/overexpression and EGFR mutations are rare in clinics, and the efficacy of dual-target therapy combined with EGFR-TKI and Savolitinib for them has not been studied yet. Here, we reported two NSCLC patients with primary MET amplification/overexpression and EGFR mutation, who benefited from T+S therapy (the dual-target therapy of EGFR-TKI plus Savolitinib) and achieved a progression-free survival (PFS) of approximately 5 months. The two cases indicated that T+S therapy has an acceptable safety profile and encouraging antitumor efficacy in NSCLC patients harboring concurrent primary MET amplification/overexpression and EGFR mutation. Meanwhile, the observation stresses the importance of genetic testing, and the MET gene needs to be detected at first diagnosis for the best choice of targeted therapies.

N6-methyladenosine (m6A) reader YTHDF2 accelerates endothelial cells ferroptosis in cerebrovascular atherosclerosis.

Cerebrovascular diseases have extreme high mortality and disability rate worldwide, and endothelial cells injury-induced atherosclerosis acts as the main cause of cerebrovascular disease. Ferroptosis is a novel type of programmed cell death depending on iron-lipid peroxidation. Recent studies have revealed that ferroptosis might promote the progression of atherosclerosis (AS). Here, this research aimed to investigate the function and its profound mechanism on vascular endothelial cells in atherosclerosis. Research results revealed that YTHDF2 expression up-regulated in ox-LDL treated human umbilical vein endothelial cells (HUVECs). Gain/loss functional assays indicated that YTHDF2 overexpression inhibited HUVECs' proliferation and accelerated the ferroptosis in ox-LDL-administered HUVECs. Meanwhile, YTHDF2 silencing promoted cell proliferation and reduced the ferroptosis in ox-LDL-administered HUVECs. Mechanistically, in silico analysis suggested that there were potential m6A-modified sites on SLC7A11 mRNA, and YTHDF2 could bind with SLC7A11 mRNA via m6A-dependent manner. YTHDF2 promoted the degradation of SLC7A11 mRNA, thereby reducing its mRNA stability. Taken together, these findings suggest that YTHDF2 accelerates endothelial cells ferroptosis in cerebrovascular atherosclerosis, helping us enhance our comprehension on cerebrovascular disease pathological physiology.

Changes in serum uric acid, serum uric acid/serum creatinine ratio, and gamma-glutamyltransferase might predict the efficacy of neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.

PURPOSE: The purpose of this study was to investigate the predictive value of changes in serum uric acid (SUA), the ratio of serum uric acid to serum creatinine (SUA/SCr), and serum gamma-glutamyltransferase (GGT) from before to after therapy in patients with locally advanced rectal cancer (LARC). METHODS: Data from 114 LARC patients from January 2016 to December 2021 were included in this retrospective study. All patients received neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME). The change in SUA was calculated as a ratio: (SUA level after nCRT-SUA level before nCRT)/SUA level before nCRT. The change ratios of SUA/SCr and GGT were calculated in the same way. The efficacy of nCRT was evaluated by magnetic resonance (MR) and postoperative pathological response. A nonlinear model was used to evaluate whether the change ratios of SUA, SUA/SCr, and GGT were associated with the efficacy of nCRT. The predictive power of the change ratios of SUA, SUA/SCr, and GGT was assessed by receiver operating characteristic (ROC) curves. Univariate and multivariate Cox regression analyses were employed to measure the associations between disease-free survival (DFS) and other predictive indicators. The Kaplan-Meier method was used to further compare DFS between groups. RESULTS: The nonlinear model indicated that the change ratios of SUA, SUA/SCr, and GGT were associated with the efficacy of nCRT. The change ratios of SUA, SUA/SCr, and GGT were used to predict the area under the ROC curve of efficacy for nCRT (0.95, 0.91-0.99), which was better than the prediction by the change ratio of SUA (0.94, 0.89-0.99), SUA/SCr (0.90, 0.84-0.96), or GGT alone (0.86, 0.79-0.93; p < 0.05). The optimal cut-off values of SUA, SUA/SCr, and GGT change were 0.02, 0.01, and 0.04, respectively. The Kaplan-Meier method indicated that patients with SUA, SUA/SCr, or GGT changes greater than the cut-off values had shorter DFS (p < 0.05). CONCLUSION: Change ratios of SUA, SUA/SCr, or GGT greater than the cut-off values implied a risk of poor pathological response after nCRT and shorter DFS in LARC patients.

Curcumol ß-cyclodextrin inclusion complex enhances radiosensitivity of esophageal cancer under hypoxic and normoxic condition.

PURPOSE: Radiotherapy is an indispensable treatment for esophageal cancer (EC), but radioresistance is not uncommon. Curcumol, as an active extract from traditional Chinese medicines, has been reported to have antitumor activity in various types of human tumor cells. However, its reversal of radioresistance has been rarely reported. MATERIALS AND METHODS: In the present study, curcumol was prepared as an inclusion complex with ß-cyclodextrin. EC cell lines were treated with radiation and curcumol ß-cyclodextrin inclusion complex (CßC), and the effect of radiosensitization of CßC was investigated in vitro and in vivo. The in vitro experiments included cell proliferation assay, clonogenic survival assay, apoptosis assay, cell cycle assay, and western blot assay. RESULTS: The in vitro data revealed that CßC and irradiation synergistically inhibited the proliferation, reduced the colony formation, promoted the apoptosis, increased the G2/M phase, inhibited DNA damage repair, and reversed the hypoxia-mediated radioresistance of EC cells to a greater extent than did CßC alone or irradiation alone. The sensitization enhancement ratios (SERs) were 1.39 for TE-1 and 1.48 for ECA109 under hypoxia. The SERs were 1.25 for TE-1 and 1.32 for ECA109 under normoxia. The in vivo data demonstrated that the combination of CßC and irradiation could inhibit tumor growth to the greatest extent compared with either monotherapy alone. The enhancement factor was 2.45. CONCLUSION: This study demonstrated that CßC could enhance radiosensitivity of EC cells under hypoxic and normoxic condition. Thus, CßC can be used as an effective radiosensitizer for EC.

Efficacy and safety of different radiotherapy doses in neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: A retrospective study.

Background: This study aims to compare the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) with different radiotherapy doses (45Gy and 50.4Gy) in patients with locally advanced rectal cancer (LARC). Methods: Herein, 120 patients with LARC were retrospectively enrolled between January 2016 and June 2021. All patients underwent two courses of induction chemotherapy (XELOX), chemoradiotherapy, and total mesorectum excision (TME). A total of 72 patients received a radiotherapy dose of 50.4 Gy, while 48 patients received a dose of 45 Gy. Surgery was then performed within 5-12 weeks following nCRT. Results: There was no statistically significant difference between the baseline characteristics of the two groups. The rate of good pathological response in the 50.4Gy group was 59.72% (43/72), while in the 45Gy group achieved 64.58% (31/48) (P>0.05). The disease control rate (DCR) in the 50.4Gy group was 88.89% (64/72), compared to 89.58% (43/48) in the 45Gy group (P>0.05). The incidence of adverse reactions for radioactive proctitis, myelosuppression, and intestinal obstruction or perforation differed significantly between the two groups (P<0.05). The anal retention rate in the 50.4Gy group was significantly higher in contrast to the 45Gy group (P<0.05). Conclusions: Patients receiving a radiotherapy dose of 50.4Gy have a better anal retention rate but also a higher incidence of adverse events such as radioactive proctitis, myelosuppression, and intestinal obstruction or perforation, and a comparable prognosis to patients treated with a radiotherapy dose of 45Gy.

Andrographolide Attenuates Blood-Brain Barrier Disruption, Neuronal Apoptosis, and Oxidative Stress Through Activation of Nrf2/HO-1 Signaling Pathway in Subarachnoid Hemorrhage.

Andrographolide (Andro), a diterpene of the labdane family extracted from the Asian plant Andrographis paniculata, is neuroprotective against stroke and Alzheimer's disease. However, whether Andro protected the brain against subarachnoid hemorrhage (SAH) was still unknown. Thus, we explored whether Andro attenuated blood-brain barrier (BBB) disruption and neuronal apoptosis and inhibited oxidative stress to protect the brain against SAH both in vitro and in vivo and detected underlying mechanisms of Andro's neuroprotective effects in the present study. Oxyhemoglobin (OxyHb)-treated neuronal PC12 cells were used as an in vitro model. An in vivo model was established using Sprague-Dawley rats. Moreover, we used an inhibitor of heme oxygenase-1 (HO-1) (ZnPPIX) in vitro and in vivo experiments to evaluate whether the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) cascade acted as one protective molecular mechanism of Andro against SAH. Our results revealed that, in vitro, Andro increased cell viability, inhibited apoptosis, and activated Nrf2/HO-1 cascade of neuronal PC12 cells treated with OxyHb. In vivo, Andro attenuated the neurological dysfunction, neuronal apoptosis, BBB disruption, brain edema, and oxidative stress and activated the Nrf2/HO-1 pathway. ZnPPIX reversed the effects of Andro in vitro and in vivo. Our research suggested that Andro alleviated BBB disruption, neuronal apoptosis, and oxidative stress in SAH, possibly via the Nrf2/HO-1 signaling pathway.

Knockdown of lncRNA MIAT attenuated lipopolysaccharide-induced microglial cells injury by sponging miR-613.

Microglia activation and its mediated neuroinflammation play an important role in the pathological process of various central nervous system injuries and diseases. Previous studies have reported abnormal expression of lncRNAs participated in neuroinflammation. However, the expression pattern and involvements of MIAT in neuroinflammatory diseases are not fully investigated. We first screened abnormal expressed lncRNAs in BV2 cells treated with LPS. The expression of MIAT in LPS-induced BV2 cells was detected by qRT-PCR. MTT assay, cell migration, flow cytometry analysis, ELISA, qRT-PCR, and Western blotting analysis were applied to evaluating the effect of si-MIAT on LPS-induced H9C2 cells. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism of lncRNA-miRNA-mRNA network. The results showed LncRNA MIAT expression was significantly increased in LPS-induced BV2 microglial cells. Besides, MIAT knockdown alleviated LPS-induced repression of cell viability and induction of apoptosis and inflammatory response in BV2 cells. Furthermore, LncRNA MIAT regulated NFAT5 expression via sponging miR-613 in LPS-induced BV2 cells. Altogether, these results suggest that lncRNA MIAT functioned as a ceRNA for miR-613 to modulate NFAT5 expression in LPS-induced BV2 cells, which may contribute to a better understanding of the mechanism of neuroinflammatory diseases.

A nomogram model to individually predict prognosis for esophageal cancer with synchronous pulmonary metastasis.

Background: Esophageal cancer (EC) is a life-threatening disease worldwide. The prognosis of EC patients with synchronous pulmonary metastasis (PM) is unfavorable, but few tools are available to predict the clinical outcomes and prognosis of these patients. This study aimed to construct a nomogram model for the prognosis of EC patients with synchronous PM. Methods: From the Surveillance, Epidemiology, and End Results database, we selected 431 EC patients diagnosed with synchronous PM. These cases were randomized into a training cohort (303 patients) and a validation cohort (128 patients). Univariate and multivariate Cox regression analyses, along with the Kaplan-Meier method, were used to estimate the prognosis and cancer-specific survival (CSS) among two cohorts. Relative factors of prognosis in the training cohort were selected to develop a nomogram model which was verified on both cohorts by plotting the receiver operating characteristic (ROC) curves as well as the calibration curves. A risk classification assessment was completed to evaluate the CSS of different groups using the Kaplan-Meier method. Results: The nomogram model contained four risk factors, including T stage, bone metastasis, liver metastasis, and chemotherapy. The 6-, 12- and 18-month CSS were 55.1%, 26.7%, and 5.9% and the areas under the ROC curve (AUC) were 0.818, 0.781, and 0.762 in the training cohort. Likewise, the AUC values were 0.731, 0.764, and 0.746 in the validation cohort. The calibration curves showed excellent agreement both in the training and validation cohorts. There was a substantial difference in the CSS between the high-risk and low-risk groups (P<0.01). Conclusion: The nomogram model serves as a predictive tool for EC patients with synchronous PM, which would be utilized to estimate the individualized CSS and guide therapeutic decisions.

Expression levels of chemokine (C-X-C motif) ligands CXCL1 and CXCL3 as prognostic biomarkers in rectal adenocarcinoma: evidence from Gene Expression Omnibus (GEO) analyses.

Rectal cancer is a life­threatening disease worldwide. Chemotherapy resistance is common in rectal adenocarcinoma patients and has unfavorable survival outcomes; however, its related molecular mechanisms remain unknown. To identify genes related to the initiation and progression of rectal adenocarcinoma, three datasets were obtained from the Gene Expression Omnibus database. In total, differentially expressed genes were analyzed from 294 tumor and 277 para-carcinoma samples from patients with rectal cancer. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functions were investigated. Cytoscape software and MicroRNA Enrichment Turned Network were applied to construct a protein-protein interaction network of the dependent hub genes and related microRNAs. The Oncomine database was used to identify hub genes. Additionally, Gene Expression Profiling Interactive Analysis was applied to determine the RNA expression level. Tumor immune infiltration was assessed using the Tumor Immune Estimation Resource database. The expression profiles of hub genes between stages, and their prognostic value, were also evaluated. During this study, data from The Cancer Genome Atlas were utilized. In rectal adenocarcinoma, four hub genes including CXCL1, CXCL2, CXCL3, and GNG4 were highly expressed at the gene and RNA levels. The expression of CXCL1, CXCL2, and CXCL3 was regulated by has-miR-1-3p and had a strong positive correlation with macrophage and neutrophil. CXCL2 and CXCL3 were differentially expressed at different tumor stages. High expression levels of CXCL1 and CXCL3 predicted poor survival. In conclusion, the CXCL1 and CXCL3 genes may have potential for prognosis and molecular targeted therapy of rectal adenocarcinoma.

Thoracic radiotherapy and concurrent almonertinib for unresectable stage III EGFR-mutated non-small-cell lung cancer: a phase 2 study.

BACKGROUND: Concurrent chemo-radiotherapy remains the standard treatment in unresectable stage III non-small-cell lung cancer (NSCLC) patients. Several studies have shown a potential value of concurrent epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with thoracic radiotherapy in EGFR-mutated population, but a high risk of radiation pneumonitis raised a major concern. This study intends to explore the safety and efficacy of concurrent almonertinib, a new third-generation EGFR-TKI, with radiotherapy in locally advanced EGFR-mutated NSCLC patients. METHODS: Locally advanced NSCLC patients harboring sensitive EGFR mutation will be included in this study. A radiotherapy plan will be made for each patient before treatment, and the lung V20 will be calculated. Patients with lung V20 ≥ 28% were enrolled in induction group (arm A), which almonertinib was given for 2 months followed by concurrent radiotherapy; patients with lung V20 < 28% were enrolled in concurrent group (arm B), which almonertinib was given concurrent with thoracic radiotherapy. The primary endpoint is the incidence of grade ≥ 3 radiation pneumonitis within 6 months post-radiotherapy, and the secondary endpoints are local control rate, progression-free survival, and overall survival. DISCUSSION: The safety and efficacy of third-generation EGFR-TKI concurrent with thoracic radiotherapy in locally advanced EGFR-mutated NSCLC is still unknown. We propose to conduct this phase 2 study evaluating the safety especially the radiation pneumonitis within 6 months post-radiotherapy. This trial protocol has been approved by the Ethics committee of Hangzhou cancer hospital. The ethics number is HZCH-2020-030. TRIAL REGISTRATION: clinicaltrials.gov, NCT04636593 . Registered 19 November 2020 - Retrospectively registered.

A novel nomogram for predicting the risk of epilepsy occurrence after operative in gliomas patients without preoperative epilepsy history.

OBJECTIVE: Epilepsy is a common complication in glioma patients after undergoing brain tumor surgery combined with chemotherapy and/or radiotherapy. Whether antiepileptic drug prophylaxis could be used in these patients remains an open question. The purpose of this study was to produce a model for predicting the risk of epilepsy occurrence in such patients. METHODS: The clinicopathologic data of glioma patients after tumor treatment were reviewed in this study. Univariate and multivariate logistic regression analyses were carried out to analyze the correlation between the clinicopathologic data and the risk of epilepsy occurrence. A nomogram was built according to the multivariate logistic regression model results. RESULTS: A total of 219 patients with gliomas were reviewed. Univariate analyses revealed that age, WHO glioma classification, CD34, EGFR, Ki67, MGMT, P53 and VIM were significantly associated with the risk of epilepsy occurrence. Multivariate analyses revealed that age, WHO glioma classification, CD34, EGFR, MGMT, and VIM were predictors of risk of epilepsy occurrence. A nomogram of the risk of epilepsy occurrence was built based on statistically significant variables from the multivariate logistic regression analysis. The c-index of the nomogram was 0.755 (95 % confidence interval (CI), 0.742-0.769). SIGNIFICANCE: This nomogram model provides reliable information about the risk of epilepsy occurrence for oncologists and neurological physicians.

Rabi resonance in coherent population trapping: microwave mixing scheme.

Coherent population trapping (CPT) resonance signals have promise in a wide range of applications involving precision sensing. Generally, the CPT phenomenon occurs in a three-level Λ system with a bichromatic phase-coherent light fields. We theoretically and experimentally studied an Rb vapor-cell-based atomic system involving bichromatic CPT optical fields and an external microwave (MW) field simultaneously. In such a mixing scheme, the coherence of the ground states could be controlled either by the Rabi frequency of the microwave field or by the relative phase between the optical fields and the MW field. Moreover, we investigated the Rabi resonance in this mixing scheme. The Rabi frequency of the MW field can be measured SI (International System of Units)-traceably based on the Rabi resonance lineshape, and thus holds the potential to realize intensity stabilization of the optical field in this system. Simple theoretical models and numerical calculations are also presented to explain the experimental results. There is scope to use the proposed technique in future development of SI-traceable optical field strength standards.

High Mean Corpuscular Volume as a Predictor of Poor Overall Survival in Patients with Esophageal Cancer Receiving Concurrent Chemoradiotherapy.

BACKGROUND: Increasing numbers of recent studies have demonstrated that high mean corpuscular volume (MCV) is a predictor of poor overall survival (OS) and therapeutic response in patients with solid tumors. The aim of the present study was to explore the association between high MCV and OS in patients with advanced esophageal cancer (EC) undergoing concurrent chemoradiotherapy. PATIENTS AND METHODS: Enrolled in this study were 249 patients with advanced EC who underwent concurrent chemoradiotherapy. Pre-treatment MCV values were collected in all patients and their correlations with OS and pathophysiological characteristics were analyzed. The chi-square test was used to explore the correlation between MCV and various clinical pathophysiological characteristics, and the prognostic significance of high MCV using Kaplan-Meier curves and the Cox proportional hazards model. All P-values were two-tailed and a P-value <0.05 was considered statistically significant. RESULTS: According to ROC curve analysis, the optimal cut-off value of MCV was 93.6 fL. The mean OS was 14.7 months in all 249 EC patients, 10.9 months in patients with MCV >93.6 fL, and 18.8 months in patients with MCV <93.6 fL; the difference is statistically significant (P<0.05). Chi-square test showed that the MCV value was correlated with the N stage of the tumor and the therapeutic effect, indicating that the higher the MCV was, the higher the T stage of the tumor and the worse the therapeutic effect would be (p=0.012 and p <0.01). Multivariate analysis showed that MCV (OR = 1.864, 95% CI: 1.439-2.415) was an independent prognostic factor for OS in EC patients. CONCLUSION: High MCV is a poor predictor of OS in patients with advanced EC receiving concurrent chemoradiotherapy.

Predictive value of neuron-specific enolase, neutrophil-to-lymphocyte-ratio and lymph node metastasis for distant metastasis in small cell lung cancer.

OBJECTIVE: To investigate the value of neuron-specific enolase (NSE), neutrophil-to-lymphocyte ratio (NLR) and lymph node metastasis in predicating distant metastasis in patients with limited-stage small cell lung cancer (LD-SCLC). METHODS: Clinical pathological data of LD-SCLC patients in the First Affiliated Hospital of Wenzhou Medical University between August 2009 and October 2017 were retrospectively analyzed. The age, gender, smoking, TNM, NSE, NLR, chemotherapy cycle, radiotherapy, surgery and new metastasis of lymph nodes of 47 cases with distant metastasis and 47 cases without distant metastasis in 1 year were compared. Finally, factors influencing distant metastasis were determined as the predictors. The receiver operating characteristic (ROC) curve model was established based on logistic regression analysis of the factors obtained. RESULTS: Distant metastasis mainly involved brain (17/47), liver (17/47) and bone (17/47). Univariate analysis showed that patients with new lymph node metastasis, high NSE, pretreatment hilar lymph node metastasis and NLR were more prone to have distant metastasis. Multivariate analysis showed that new lymph node metastasis, high NSE, NLR and pretreatment hilar lymph node metastasis were independent predictors. The predictive model established using these predictors had an AUC of 0.872 (95%CI: 0.803-0.941), a sensitivity of 76.60% and a speciality of 80.85%. CONCLUSION: The new lymph node metastasis, NLR and NSE are predictors of distant metastasis, and thus, may have a profound impact on treatment decision making. Patients with lower NLR and NSE expression levels and less new metastasis of lymph nodes have a lower distant metastasis rate.

Immune checkpoint inhibitor induces cardiac injury through polarizing macrophages via modulating microRNA-34a/Kruppel-like factor 4 signaling.

Cancer immunotherapy has become a well-established treatment option for some cancers; however, its use is hampered by its cardiovascular adverse effects. Immune checkpoint inhibitors (ICIs)-related cardiac toxicity took place in kinds of different forms, such as myocarditis, acute coronary syndrome, and pericardial disease, with high mortality rates. This study aimed to investigate the roles of programmed death-1 (PD-1) inhibitor, one of widespread used ICIs, in the development of murine cardiac injury. PD-1 inhibitor is known to transduce immunoregulatory signals that modulate macrophages polarization to attack tumor cells. Hence, this study explored whether the cardiovascular adverse effects of PD-1 inhibitor were related to macrophage polarization. MicroRNA-34a (miR-34a), which appears to regulate the polarization of cultured macrophages to induce inflammation, is examined in cardiac injury and macrophage polarization induced by the PD-1 inhibitor. As a target of miR-34a, Krüppel-like factor 4 (KLF4) acted as an anti-inflammation effector to take cardiac protective effect. Further, it investigated whether modulating the miR-34a/KLF4-signaling pathway could influence macrophage polarization. The PD-1 inhibitor markedly induced M1 phenotype macrophage polarization with impaired cardiac function, whereas miR-34a inhibitor transfection treatment reversed M1 polarization and cardiac injury in vivo. In vitro, PD-1 inhibitor-induced M1 polarization was accompanied by an increase in the expression of miR-34a but a decrease in the expression of KLF4. TargetScan and luciferase assay showed that miR-34a targeted the KLF4 3'-untranslated region. Either miR-34a inhibition or KLF4 overexpression could abolish M1 polarization induced by the PD-1 inhibitor. The findings strongly suggested that the PD-1 inhibitor exerted its effect in promoting M1 polarization and cardiac injury by modulating the miR-34a/KLF4-signaling pathway and inducing myocardial inflammation. These findings might help us to understand the pathogenesis of cardiac injury during immunotherapy, and provide new targets in ameliorating cardiac injury in patients with cancer receiving PD-1 inhibitor treatment.

MicroRNA-7 as a Potential Biomarker for Prognosis in Pancreatic Cancer.

MicroRNAs play critical roles in tumor progression. Our recent study has indicated that microRNA-7 (miR-7) impairs autophagy-derived pools of glucose to suppress the glycolysis in pancreatic cancer progression. However, the roles of miR-7 in clinical significance and chemoresistance of pancreatic cancer remain unexplored. The aim of this study was to assess the expression of miR-7 in patients with pancreatic cancer and to evaluate the possibility of its usage as a prognostic molecular biomarker. MicroRNA array-based quantification analysis of 372 miRNAs was compared in serum between pancreatic cancer and healthy individuals, gemcitabine-sensitive and gemcitabine-resistance patients. We identified miR-7 showed the potential predictive power for gemcitabine-sensitive patients with pancreatic cancer. Then, the results were validated in pancreatic tissue microarray and The Cancer Genome Atlas (TCGA) dataset, demonstrating that lower miR-7 expression was correlated with more advanced tumor stages and worse prognosis in pancreatic cancer. The Cox proportional-hazards model analysis identified miR-7 to be an independent variable for prediction of the survival. Furthermore, the mechanistic exploration suggested the clinical significance of miR-7 involved its interference effect on autophagy and glycolysis in pancreatic cancer using pancreatic cancer tissue microarrays and TCGA data. Therefore, the results of the present study provide evidences that low microRNA-7 expression may contribute to tumor progression and poor prognosis in pancreatic cancer.

Folate-conjugated herpes simplex virus for retargeting to tumor cells.

BACKGROUND: Herpes simplex virus type 1 (HSV-1)-mediated oncolytic therapy is a promising cancer treatment modality. However, viral tropism is considered to be one of the major stumbling blocks to the development of HSV-1 as an anticancer agent. METHODS: The surface of oncolytic HSV-1 G207 was covalently modified with folate-poly (ethylene glycol) conjugate (FA-PEG). The specificities and tumor targeting efficiencies of modified or unmodified G207 particles were analyzed by a real-time polymerase chain reaction at the level of cell attachment and entry. Immune responses were assessed by an interleukin-6 release assay from RAW264.7 macrophages. Biodistribution and in vivo antitumoral activity after intravenous delivery was evaluated in BALB/c nude mice bearing subcutaneous KB xenograft tumors. RESULTS: FA-PEG-HSV exhibited enhanced targeting specificity for folate receptor over-expressing tumor cells and had lower immunogenicity than the unmodified HSV. In vivo, the FA-PEG-HSV group revealed an increased anti-tumor efficiency and tumor targeting specificity compared to the naked HSV. CONCLUSIONS: These results indicate that folate-conjugated HSV G207 presents a folate receptor-targeted oncolytic virus with a potential therapeutic value via retargeting to tumor cells.

Screening key lncRNAs and mRNAs for left-sided and right-sided colon adenocarcinoma based on lncRNA-mRNA functional synergistic network.

BACKGROUND: The difference between right-sided colon adenocarcinoma (RSCOAD) and left-sided colon adenocarcinoma (LSCOAD) patients has been a controversial issue. The purpose of this study was to screen key lncRNAs and mRNAs in RSCOAD and LSCOAD. METHODS: We used The Cancer Genome Atlas (TCGA) data to screen differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs). The optimal diagnostic lncRNA biomarkers for RSCOAD and LSCOAD were identified using Boruta algorithm. DEmRNA-DElncRNA interaction analysis was constructed. DEmRNAs co-expressed with DElncRNAs were functionally annotated. The expression of selected DElncRNAs and DEmRNAs were verified by qRT-PCR. RESULTS: A total of 2,672 DEmRNAs (1,050 down-regulated and 1,622 up-regulated mRNAs) and 453 DElncRNAs (139 down-regulated and 314 up-regulated lncRNAs) between RSCOAD and LSCOAD were identified. We also obtained 31 optimal diagnostic lncRNAs biomarkers in RSCOAD compared to LSCOAD. The AUC of the random forests model was 0.902 and the specificity and sensitivity of this model were 83.5% and 82.1%, respectively. Three DElncRNAs (HAGLR, HOXB-AS3 and SATB2-AS1) and three DEmRNAs (HOXD1, HOXB3 and SATB2) were identified as key DElncRNAs and DEmRNAs, respectively. Age, residual tumor, stage, and M were independent predictors of survival. The qRT-PCR analysis were consistent with our TCGA integration analysis, generally. CONCLUSIONS: HOXD1, HOXB3 and SATB2, HAGLR, HOXB-AS3 and SATB2-AS1 may be involved in the pathogenesis of RSCOAD and LSCOAD, and may contribute to the understanding of the pathological mechanism of RSCOAD and LSCOAD.

Phenotypic changes of interstitial cells of Cajal after intestinal obstruction in rat model.

The objective was to study the effect of mechanical intestinal obstruction in rats on the phenotype of interstitial cells of Cajal (ICC). Healthy Wistar rats were randomly divided into sham-operation group (C), one day obstruction group (M1), two days obstruction group (M2), and three days obstruction group (M3), with 10 rats in each group. The expression of SCF mRNA and c-Kit protein in intestinal tissue was investigated by RT-PCR and immunohistochemistry. Compared with the sham-operation group, the relative expression of SCF mRNA and the expression of c-Kit protein in intestinal tissue were significantly decreased in both obstruction groups. Levels decreased gradually with the prolongation of obstruction time, and significantly decreased on the 3rd day after obstruction (P<0.05). Immunohistochemical staining of the small intestine showed that the number of ICC in the sham-operation group was the highest, and they were gradually decreased with the extension of obstruction time in the M1 to M3 groups. There was a significant difference between groups (P<0.05). Intestinal obstruction caused a decrease in the concentrations of SCF mRNA and c-Kit protein in ICC. With the prolongation of intestinal obstruction, the number of ICCs gradually decreased.