Hyperspectral digital holography realized by using an electro-optical frequency comb via injection locking.

Hyperspectral digital holography (HSDH) is a versatile holographic imaging technique that offers large unambiguous depth range and spectroscopic information. In this Letter, we propose a novel, to the best of our knowledge, HSDH system that is realized by using an electro-optical frequency comb (EOFC) via injection locking. In comparison with conventional dual-comb HSDH, the proposed system only requires one EOFC and few other devices, which not only simplifies the system structure and reduces the cost but also improves the imaging speed. We validated the system using an EOFC with 20 optical frequencies spaced at 18 GHz intervals. In a total measurement time of 0.5 s, we successfully captured images of two targets that were 0.74 mm apart without phase ambiguity and obtained the transmission spectrum of an absorbing gas simultaneously. This work provides valuable insights for HSDH systems relying on an optical frequency comb.

Exercise-induced IL-15 acted as a positive prognostic implication and tumor-suppressed role in pan-cancer.

Objective: Exercise can produce a large number of cytokines that may benefit cancer patients, including Interleukin 15 (IL-15). IL-15 is a cytokine that has multiple functions in regulating the adaptive and innate immune systems and tumorigenesis of lung and breast cancers. However, the roles of IL-15 in other types of cancer remain unknown. In this article, we try to systematically analyze if IL-15 is a potential molecular biomarker for predicting patient prognosis in pan-cancer and its connection with anti-cancer effects of exercise. Methods: The expression of IL-15 was detected by The Cancer Genome Atlas (TCGA) database, Human protein Atlas (HPA), and Genotype Tissue-Expression (GTEX) database. Analysis of IL-15 genomic alterations and protein expression in human organic tissues was analyzed by the cBioPortal database and HPA. The correlations between IL-15 expression and survival outcomes, clinical features, immune-associated cell infiltration, and ferroptosis/cuproptosis were analyzed using the TCGA, ESTIMATE algorithm, and TIMER databases. Gene Set Enrichment Analysis (GSEA) was performed to evaluate the biological functions of IL-15 in pan-cancer. Results: The differential analysis suggested that the level of IL-15 mRNA expression was significantly downregulated in 12 tumor types compared with normal tissues, which is similar to the protein expression in most cancer types. The high expression of IL-15 could predict the positive survival outcome of patients with LUAD (lung adenocarcinoma), COAD (colon adenocarcinoma), COADREAD (colon and rectum adenocarcinoma), ESCA (esophageal carcinoma), SKCM (skin cutaneous melanoma), UCS (uterine carcinosarcoma), and READ (rectum adenocarcinoma). Moreover, amplification was found to be the most frequent mutation type of IL-15 genomic. Furthermore, the expression of IL-15 was correlated to the infiltration levels of various immune-associated cells in pan-cancer assessed by the ESTIMATE algorithm and TIMER database. In addition, IL-15 is positively correlated with ferroptosis/cuproptosis-related genes (ACSL4 and LIPT1) in pan-cancer. Levels of IL-15 were reported to be elevated in humans for 10-120 min following an acute exercise. Therefore, we hypothesized that the better prognosis of pan-cancer patients with regular exercise may be achieved by regulating level of IL-15. Conclusion: Our results demonstrated that IL-15 is a potential molecular biomarker for predicting patient prognosis, immunoreaction, and ferroptosis/cuproptosis in pan-cancer and partly explained the anti-cancer effects of exercise.

Clinical value and application of a novel nomogram containing inflammatory, nutritional and clinical markers in predicting overall survival of stage II/III gastric cancer patients after radical resection: a bi-centered retrospective study of 2,443 patients.

OBJECTIVES: We aimed to identify nutritional, inflammatory and clinical indicators associated with stage II/III gastric cancer in patients, and construct a nomogram model for accurate prediction of prognosis of patients. METHODS: We retrospectively recruited stage II/III gastric cancer (GC) patients who underwent radical gastrectomy at Fudan University Shanghai Cancer Center, from 2012 to 2019. The patients were randomly divided into training and internal validation sets, and then the Maximum log-rank statistic method was used to determine the optimal cut-off value. Next, we performed univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival (OS). These were subsequently used to develop a nomogram model. We validated this model in patients with stage II/III gastric cancer (from 2010 to 2019) at Guangxi Medical University Affiliated Tumor Hospital. RESULTS: A total of 2,443 patients met our inclusion criteria and were therefore included in our study. Patients from Fudan University Shanghai Cancer Center were randomly divided into training (n=1725) and internal validation (n=430) sets, while those from Guangxi Medical University Affiliated Tumor Hospital were used as the external validation set (n=288). Results from univariate and multivariate Cox regression analyses revealed that age (adjusted HR, 1.23; 95% CI, 1.05-1.44; P=0.012), TNM stage (adjusted HR, 3.62; 95% CI, 2.79-4.68; P<0.001), CEA (adjusted HR, 1.40; 95% CI, 1.14-1.71; P<0.001), CA199 (adjusted HR, 1.47; 95% CI, 1.21-1.79; P<0.001), and Prognostic Nutritional Index (PNI, adjusted HR, 0.81; 95% CI, 0.67-0.98; P=0.026) were independent prognostic factors for OS in the training set. The established nomogram model, with a C-index of 0.67, had 3- and 5-year Area under Curve (AUC) values of 0.719 and 0.714, respectively. Notably, the model effectively distinguished patients' OS in both the internal (P<0.001) and external (P<0.001) datasets. CONCLUSIONS: PNI is an independent prognostic factor for stage II/III GC patients after radical resection. The established novel nomogram model, based on nutritional, inflammatory and clinical indicators, can accurately and efficiently predict prognosis of stage II/III GC patients.

Plasmonic Ag Nanoparticle-Loaded n-p Bi2O2CO3/α-Bi2O3 Heterojunction Microtubes with Enhanced Visible-Light-Driven Photocatalytic Activity.

In this study, n-p Bi2O2CO3/α-Bi2O3 heterojunction microtubes were prepared via a one-step solvothermal route in an H2O-ethylenediamine mixed solvent for the first time. Then, Ag nanoparticles were loaded onto the microtubes using a photo-deposition process. It was found that a Bi2O2CO3/α-Bi2O3 heterostructure was formed as a result of the in situ carbonatization of α-Bi2O3microtubes on the surface. The photocatalytic activities of α-Bi2O3 microtubes, Bi2O2CO3/α-Bi2O3 microtubes, and Ag nanoparticle-loaded Bi2O2CO3/α-Bi2O3 microtubes were evaluated based on their degradation of methyl orange under visible-light irradiation (λ > 420 nm). The results indicated that Bi2O2CO3/α-Bi2O3 with a Bi2O2CO3 mass fraction of 6.1% exhibited higher photocatalytic activity than α-Bi2O3. Loading the microtubes with Ag nanoparticles significantly improved the photocatalytic activity of Bi2O2CO3/α-Bi2O3. This should be ascribed to the internal static electric field built at the heterojunction interface of Bi2O2CO3 and α-Bi2O3 resulting in superior electron conductivity due to the Ag nanoparticles; additionally, the heterojunction at the interfaces between two semiconductors and Ag nanoparticles and the local electromagnetic field induced by the surface plasmon resonance effect of Ag nanoparticles effectively facilitate the photoinduced charge carrier transfer and separation of α-Bi2O3. Furthermore, loading of Ag nanoparticles leads to the formation of new reactive sites, and a new reactive species ·O2− for photocatalysis, compared with Bi2O2CO3/α-Bi2O3.

Human mesenchymal stem cell derived exosomes inhibit the survival of human melanoma cells through modulating miR-138-5p/SOX4 pathway.

Melanoma, a skin cancer derived from malignant melanocytes, is characterized by high aggressiveness and mortality. However, its exact etiology is unknown. Recently, the roles of exosomes and exosomal microRNAs (miRNAs) in the progression and therapy of various disorders, including melanoma, have gained attention. We investigated the impact of miR-138-5p from exosomes released by human mesenchymal stem cells (HMSCs) on the pathogenesis of melanoma. We isolated exosomes from HMSCs (HMSC-exos) by ultracentrifugation and verified them by specific biomarkers and transmission electron microscopy. We used CCK8, flow cytometry, quantitative real-time PCR (qRT-PCR), and Western blots to investigate cell proliferation, apoptosis, and mRNA and protein levels, respectively. Additionally, we used luciferase assays to examine the relationship between miR-138-5p and SOX4. Administration of HMSC-exos dramatically repressed the growth of melanoma cells. Elevated miR-138-5p levels in HMSC-exos were linked to increased cell apoptosis, and miR-138-5p downregulation had the opposite effects on cells. SOX4 was targeted by miR-138-5p through direct binding to the SOX4 3'UTR. In melanoma tissues, miR-138-5p was downregulated, and SOX4 was upregulated and was negatively correlated. MiR-138-5p plays a crucial role in melanoma progression. The negative regulation of SOX4 transcription mediates the function of miR-138-5p. These findings provide a novel concept of melanoma pathogenesis and identify a valuable target (miR-138-5p/SOX4 axis) in treating this disease.

NTF4 stimulates the progression of gastric cancer via regulating FOXL1.

PURPOSE: To elucidate the diagnostic and prognostic potentials of NTF4 in gastric cancer (GC), as well as its regulatory effects on biological functions of GC cells. METHODS: Fifty-two GC patients treated by surgical resection were retrospectively analyzed and their cancer and adjacent tissues were collected. NTF4 levels in GC tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between NTF4 and clinical features of GC was analyzed. After knockdown of NTF4, the proliferative and migratory abilities of MKN45 and BGC-823 cells, and growth rate of GC in nude mice were examined. In addition, the target gene of NTF4, FOXL1 was confirmed by dual-luciferase reporter assay, and co-regulation on GC process was determined by rescue experiments. RESULTS: NTF4 was upregulated in GC tissues than in normal ones. High level of NTF4 predicted malignant progression, poor overall survival and progression-free survival in GC patients. Knockdown of NTF4 attenuated the in vitro proliferative and migratory abilities of GC cells, as well as in vivo tumorigenicity of GC in nude mice. FOXL1 was the target gene of NTF4, which was lowly expressed in GC. Knockdown of FOXL1 was able to reverse the influence of silenced NTF4 on the biological functions of GC cells. CONCLUSIONS: NTF4 is an effectively diagnostic biomarker for early-stage GC, and it stimulates the proliferative and migratory potentials in GC by negatively regulating FOXL1.

RNF180 Inhibits Proliferation and Promotes Apoptosis of Colorectal Cancer Through Ubiquitination of WISP1.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths globally and is biologically and clinically heterogeneous. Due to lack of gene expression signatures for risk and prognosis stratification of CRC, identifying novel molecular biomarkers and therapeutic targets may potentially improve CRC prognosis and treatment. RNF180 has been shown to play key contributions to the development of several types of cancers. In the current study, we investigate its role in CRC. In this study, we show that RNF180 expression was significantly downregulated in human CRC tumors and cell lines. Overexpression of RNF180 in CRC cells markedly inhibited cell viability and induced cell apoptosis, while depletion of RNF180 dramatically enhanced cell survival. Moreover, WISP1 was found to be the critical downstream molecule that mediated the tumor suppressive effects of RNF180. Mechanistically, RNF180 ubiquitinated WISP1, resulting in WISP1 downregulation and ultimately leading to suppression of CRC tumor growth in patient-derived xenograft (PDX) mouse models. Last, 5-FU and RNF180 had synergetic effect on the apoptosis induction and tumor growth inhibition. Our findings revealed a crucial role of RNF180 in suppressing tumor growth by ubiquitinating WISP1 in CRC.

TRIM58 suppresses the tumor growth in gastric cancer by inactivation of ß-catenin signaling via ubiquitination.

Objective: To investigate and define the underlying molecular mechanism of tripartite motif-containing 58 (TRIM58) in regulating the tumor growth of gastric cancer (GC).Methods: TRIM58 expression in GC tissues and cells was detected by real-time PCR and Western blot, followed by lentiviral-induced overexpression or knockdown of TRIM58. Subsequently, CCK8, BrdU-ELISA, flow cytometry, immunoprecipitation, in vitro animal experiments and immunochemistry were performed to explore the function of TRIM58. Western blotting was used to detect ß-catenin, C-myc, Cyclin D1, and survivin expression.Results: TRIM58 expression was significantly reduced in tumor tissues of GC patients and GC cell lines, whereas ß-catenin, C-myc, Cyclin D1, and survivin were highly expressed. Overexpression of TRIM58 in GC cells resulted in decreases in ß-catenin, C-myc, Cyclin D1, and survivin protein expression and significantly suppressed proliferation by preventing cell-cycle progression and promoting cell apoptosis. Conversely, TRIM58 knockdown resulted in the opposite effects. Furthermore, the effect of TRIM58 knockdown on GC cells was potently reversed by a ß-catenin inhibitor, XAV939. Immunoprecipitations showed the interaction between TRIM58 and ß-catenin, and TRIM58 overexpression significantly enhanced ß-catenin degradation. In addition, we found a significant decrease in the growth and weight of tumors and an increase in tumor cell apoptosis in TRIM58-overexpression nude mice, which were also accompanied by reduced ß-catenin expression.Conclusions: These data suggest that TRIM58 may function as a tumor suppressor in GC and potentially suppress the tumor growth of gastric cancer by inactivation of ß-catenin signaling via ubiquitination.

Identification and external validation of a novel miRNA signature for lymph node metastasis prediction in submucosal-invasive gastric cancer patients.

Endoscopic resection (ER) has been increasingly performed in the treatment of early gastric cancer (GC). However, lymph node metastasis (LNM) can cause treatment failure with ER, especially in T1b patients. Here, we attempted to develop a miRNA-based classifier to detect LNM in T1b patients. Based on high-throughput data from The Cancer Genome Atlas, we identified 20 miRNAs whose expression significantly changed in T1-2 GC with LNM vs T1-2 GC without LNM. We then developed a miRNA signature to predict LNM of T1b GC using the LASSO model and backward step wise elimination approach in a training cohort. Furthermore, the predictive accuracy of this classifier was validated in both an internal testing group of 63 patients and an external independent group of 114 patients. This systematic and comprehensive in silico study identified a 7-miRNA signature with an area under the receiver operating characteristic curve (AUROC) value of 0.843 in T1-2 GC and 0.911 in T1 EGC. The backward elimination was further used to develop a 4-miRNA (miR-153-3p, miR-708, miR-940 and miR-375) risk-stratification model in the training cohort with an AUROC value of 0.898 in cohort 2. When pathologic results were used as a reference, the risk model yielded AUROC values of 0.829 and 0.792 in two cohorts of endoscopic biopsy specimens. This novel miRNA-LNM classifier works better than the currently used pathologic criteria of ER in T1b EGC. This classifier could individualize the management of T1b patients and facilitate treatment decisions.

Study protocol of a randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma: PREACT.

BACKGROUND: The prognosis of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma is still dismal. There are no standard treatment strategies for these patients. Multidisciplinary team (MDT) approach is a good choice for making a high-quality decision. Generally, MDT will recommend these patients to receive preoperative chemotherapy or preoperative chemoradiation based on all kinds of treatment guidelines. However, the preferred preoperative treatment is still not established. In order to solve this problem, we carry out this randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. METHODS: Eligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma are randomized to receive preoperative chemoradiation or preoperative chemotherapy, followed by surgery and postoperative chemotherapy. In the preoperative chemoradiation arm (Pre-CRT), patients receive two cycles of S-1 and oxaliplatin (SOX), chemoradiation, then followed by surgery and three more cycles of SOX chemotherapy. In the preoperative chemotherapy arm (Pre-CT), patients receive three cycles of SOX, following surgery three more cycles of SOX are given. The primary endpoint of this trial is to verify that preoperative chemoradiation could significantly improve the 3-year disease free survival (DFS) of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma compared to preoperative chemotherapy. DISCUSSION: The results from this trial will provide important information about whether preoperative chemoradiation could improve survival compared to preoperative chemotherapy among patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03013010. First posted January 6, 2017.

Homeobox B7 accelerates the cancer progression of gastric carcinoma cells by promoting epithelial-mesenchymal transition (EMT) and activating Src-FAK pathway.

Aim: To study the carcinogenetic mechanism of HOXB7 in gastric cancer (GC) remains. Methods: Two human GC cell lines - SGC7901 and SNU1 - were used for this study. SGC7901 cells were transfected with siRNA-HOXB7 (siHOXB7) to knock down HOXB7 expression, whereas, SNU1 cells were transduced with pCDNA3.1-HOXB7 to overexpress HOXB7. After transfection, cancer progression was assessed by determining cell proliferation, wound-healing process, cell cycle, apoptosis, invasion, and migration. The effect of HOXB7 on epithelial-mesenchymal transition (EMT) was measured by observing changes in F-actin cytoskeleton and evaluating the expression of EMT markers. p-Scr and p-FAK were evaluated to assess the mechanism. Results: Knockdown of HOXB7 suppressed cell proliferation, alleviated the wound-healing process, inhibited cell migration and invasion, and arrested the cell cycle while promoting cell apoptosis, suggesting the tumor-suppressive effect of siHOXB7 in human GC cells. On the contrary, HOXB7 overexpression showed a tumor-promoting effect on human GC cells. Moreover, we confirmed an inhibitory effect of siHOXB7 on the EMT process by preventing epithelial cells from acquiring a mesenchymal phenotype and downregulating mesenchymal markers (vimentin, ß-catenin, N-cadherin, Twist) while upregulating epithelial markers (E-cadherin). Our data revealed that HOXB7 was associated with Src/FAK and favored the activation of the Src-FAK pathway in human GC cells. Conclusion: HOXB7 accelerated the malignancy of GC, by facilitating EMT and regulating the Scr-FAK pathway.

Comparative efficacy and safety of antiplatelet agents in cerebral ischemic disease: A network meta-analysis.

We performed a network meta-analysis (NMA) to enhance the corresponding evidence of the relative efficacy and safety of different antiplatelet agents in cerebral ischemic disease. PubMed and EMBASE were searched systematically for relevant studies. Outcomes were compared using odds ratios and 95% credible intervals. Each agent was ranked according to the value of surface under the cumulative ranking curve (SUCRA). Publication bias was evaluated by funnel plots, while consistency between direct and indirect comparison was analyzed by node-splitting and heat plots. Besides, the clustering technique was used to categorize similar agents. A number of 44 eligible studies with 148 578 patients were included in this NMA. In terms of efficacy (including mortality, recurrent stroke, and vascular event), all six interventions were better than placebo. clopidogrel (Clop) and aspirin (ASA)+Clop were the best two interventions from SUCRA. However, the performance of ASA+Clop declined significantly when considering safety (including myocardial infarction, all-cause withdrawal, and intracranial hemorrhage), especially worse in intracranial hemorrhage. In conclusion, Clop was potentially the most preferable treatment for preventing cerebral ischemic in terms of efficacy and safety. However, the addition of ASA was associated with a potential increase in intracranial hemorrhage, therefore, combination therapy of ASA and Clop should be introduced with caution although it may be more effective than the monotherapy of ASA.

microRNAs expression profile related with response to preoperative radiochemotherapy in patients with locally advanced gastric cancer.

BACKGROUND: It is urgent to find some biochemical markers for predicting the radiochemotherapy sensitivity. microRNAs have a huge potential as a predictive biomarker in gastric cancer. The current study aims to identify the microRNAs related to the radiochemotherapy sensitivity in gastric cancer. METHODS: From April 2012 to August 2014, 40 patients with locally advanced gastric cancer were included into the clinical trial in the Fudan University Shanghai Cancer Center. The lesion specimens of 15 patients were obtained by gastroendoscopy before treatment, and the RNA was extracted. microRNAs array was used to identify the microRNAs with different expression level between sensitive group and non-sensitive group. The microRNAs identified in the array were further confirmed by TaqMan Real-time PCR. RESULTS: 2006 microRNAs were identified by microRNA array, including 302 highly expressed microRNAs and 1704 lowly expressed microRNAs between non-sensitive group and sensitive group. According to the statistical significance (p < 0.05) and expression level (more than twofold or less than 0.5 times), 9 microRNAs were identified. Finally, we chose 6 microRNAs like miR-16-2-3p, miR-340-5p, miR-338-3p, miR-142-3p, miR-142-5p and miR-582-5p to determine the sensitive group and non-sensitive group. TaqMan Real-time PCR confirmed the results of microRNA array. CONCLUSIONS: microRNA array can be used to select the microRNAs associated with radiochemotherapy sensitivity in gastric cancer. miR-338-3p and miR-142-3p may be promising predictive biomarkers for such patients. TRIAL REGISTRATION: Trial Registration number: NCT03013010 . Name of registry: Phase II Study of Neoadjuvant Chemotherapy Wtih S1 + Oxaliplatin (SOX) Regimen Followed by Chemoradiation Concurrent With S-1 in Patients With Potentially Resectable Gastric Carcinoma. Date registered: December 31, 2013. The trial was prospectively registered.

Interleukin-15 suppresses gastric cancer liver metastases by enhancing natural killer cell activity in a murine model.

Interleukin (IL)-15 is a promising cytokine for cancer immunotherapy as it is a critical factor for the proliferation and activation of natural killer (NK) cells. Previous studies have suggested critical roles of IL-15 in tumor invasion and metastasis. However, the association between IL-15 and liver metastasis of gastric cancer (LMGC) remains unknown. The present study investigated the therapeutic efficacy of recombinant mouse IL-15 (rmIL-15) in murine LMGC models, in which stable green fluorescent protein (GFP)-expressing MKN45 cells (MKN45-GFP cells) were injected into the spleen parenchyma of mice for liver metastasis. At different treatments (high dose group: 2.5 µg of rmIL-15; low dose group: 0.2 µg of rmIL-15; control group: PBS), it was found that rmIL-15 decreased the formation of liver metastasis sites. Additionally, this treatment lead to improved survival of mice following tumor cell transplantation. Treatment with a high dose of rmIL-15 provided greater therapeutic efficacy by prolonged survival of the mice compared with low dose group and control group. It was found that NK cells isolated from the liver that received the high dose of rmIL-15 showed stronger cytotoxic activity compared with the other two groups on the target cells. These findings hold significant importance for the use of IL-15 as a potential adjuvant/therapeutic for liver metastasis from gastric cancer.

MiR-124-3p suppresses bladder cancer by targeting DNA methyltransferase 3B.

This study was aimed to uncover the effects of miR-124-3p on bladder cancer (BC) by regulating DNA methyltransferase 3B. The expressions of miR-124-3p and DNMT3B mRNA in BC tissues and cell lines were detected using RT-PCR. The expression of DNMT3B in cells was determined using Western blot and immunohistochemistry in tissues. In addition, chromogenic in situ hybridization staining was used to measure the expression of miR-124-3p in tissues. BC cells were transfected with miR-124-3p mimics, miR-124-3p inhibitors, DNMT3B siRNAs, and DNMT3B cDNAs + miR-124-3p mimics. Subsequently, cell proliferation, apoptosis, migration, and invasion were measured using CCK-8, the cytometry test, wound healing assay, and Transwell assay, respectively. Finally, the relationship between miR-124-3p and DNMT3B was confirmed using dual luciferase reporter gene assay. MiR-124-3p expression was significantly lower and the level of DNMT3B was significantly higher in BC tissues and cell lines compared with the normal controls. MiR-124-3p was verified to target DNMT3B. The transfection of miR-124-3p mimics and DNMT3B siRNAs down-regulated BC cell proliferation, migration, and invasion, as well as induced cell apoptosis; miR-124-3p inhibitors promoted BC cell proliferation, migration, invasion, and reduced cell apoptosis; and the effects of DNMT3B cDNAs can be compromised by miR-124-3p mimics. Thus, we concluded that miR-124-3p could suppress the proliferation, migration, invasion, and promote apoptosis of BC cells by targeting DNMT3B.

MiR-374b Promotes Proliferation and Inhibits Apoptosis of Human GIST Cells by Inhibiting PTEN through Activation of the PI3K/Akt Pathway.

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR-374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

Adjuvant chemoradiotherapy versus adjuvant chemotherapy for R1 resected gastric cancer: a retrospective cohort study.

OBJECTIVE: The aim of this study was to compare the effects of adjuvant chemoradiotherapy (CRT) and adjuvant chemotherapy (ChT) on the survival of locally advanced gastric cancer (LAGC) patients treated with R1 resection. METHODS: The patients with LAGC and microscopically positive margins after a potentially curative gastrectomy in Fudan University Shanghai Cancer Centre were retrospectively identified. The patients who were referred to our hospital for adjuvant CRT after an R1 resection elsewhere were also included. The patients were divided into either the CRT group or ChT group according to the treatment strategy. We, then, examined the patient survival results and patterns of recurrence for each group. RESULTS: There were 114 LAGC patients treated with an R1 resection identified (CRT, n = 33; ChT, n = 81). The baseline characteristics between the two groups were not different. The estimated 3 year recurrence-free survival and overall survival in the CRT and ChT groups were 45.1% vs 31.8% (p = 0.09) and 49.6% vs 39.4% (p = 0.20), respectively. The results indicated that only nodal status was an independent prognostic factor (hazard ratio 4.04, 95% confidence interval 2.06-7.93). The risk of locoregional recurrence was increased in the ChT group. The subgroup analysis revealed that patients with pN0-2 GC showed a better recurrence-free survival due to adjuvant CRT (hazard ratio 0.19, 95% confidence interval 0.04-0.90; p = 0.022). CONCLUSION: Adjuvant CRT improves locoregional control and may benefit patients with pN0-2 GC after R1 resection. The nodal status may be the most important predictor for patient selection. Advances in knowledge: Nodal status may be the most important predictor for patient selection. Compared with adjuvant ChT, LAGC patients with pN0-2 disease may further benefit from additional radiotherapy after R1 resection.

A mixed treatment comparison of toxicity of gemcitabine combined with different targeted drugs in the treatment of advanced or metastatic pancreatic cancer.

The mixed treatment comparison study was performed in order to compare the toxicities of Gemcitabine and different targeted drug combinations in the treatment of advanced/metastatic pancreatic cancer (PC). Searches were performed from the inception of PubMed and Cochrane Library databases to February 2017. This study included randomized controlled trials (RCTs) of Gemcitabine and different targeted drug combinations in the treatment of advanced/metastatic PC. Odds ratio (OR) values were calculated by direct and indirect comparisons, and the surface under the cumulative ranking curves (SUCRA) were drawn. A total of six RCTs were finally incorporated into the study. These studies included six therapy regimens: Gemcitabine + Axitinib, Gemcitabine + Trametinib, Gemcitabine + Sorafenib, Gemcitabine + Bevacizumab, Gemcitabine + Erlotinib and Gemcitabine + Tipifarnib. The results showed that Gemcitabine + Axitinib combinations showed lower incidence rates of rashes (all grades) in comparison to Gemcitabine + Trametinib and Gemcitabine + Erlotinib combinations. Compared with Gemcitabine+ Trametinib combinations, Gemcitabine + Axitinib combinations showed lower incidence rates of diarrhea (grade ≥ 3). Moreover, the cluster analyses results revealed that Gemcitabine + Axitinib combinations and Gemcitabine + Sorafenib combinations showed lower incidence rates of hematotoxicity, while Gemcitabine + Axitinib combinations showed lower incidence rates of non-hematotoxicity. Collectively, the data provided strong evidence of Gemcitabine + Axitinib combinations showing lower incidence rates of non-hematotoxicity, and Gemcitabine + Axitinib and Gemcitabine + Sorafenib combinations may have lower incidence rates of hematotoxicity in the treatment of advanced/metastatic PC.

Correlations of IGF-1R and COX-2 Expressions with Ras and BRAF Genetic Mutations, Clinicopathological Features and Prognosis of Colorectal Cancer Patients.

This case-control study aims to investigate the correlations of insulin-like growth factor receptor 1 (IGF-1R) and cyclooxygenase 2 (COX-2) expressions with Ras and BRAF genetic mutations, clinicopathological features and prognosis of colorectal cancer (CRC) patients. A total of 213 CRC patients (case group) and 200 healthy individuals (control group) were selected from our hospital. Ras (K-Ras/N-Ras) and BRAF genetic mutations were detected by direct sequencing. The positive expression rates of IGF-IR and COX-2 in CRC and normal tissues were detected using immunohistochemistry. RT-qPCR and Western blotting were applied to detect the mRNA and protein expressions of IGF-IR and COX-2 in CRC tissues and normal tissues. Total mutation rate of N-Ras, BRAF and K-Ras in case group were 5.2%, 12.2% and 47.4%, respectively. The expressions of IGF-IR and COX-2 were higher in CRC tissues with Ras and BRAF mutations than in those without. CRC tissues with Ras mutation showed higher COX-2 expression than those with BRAF mutation. IGF-IR and COX-2 expressions were correlated to infiltration degree, lymphatic metastasis (in CRC tissues with and without Ras and BRAF mutations), and Dukes stages (only in CRC tissues with Ras and BRAF mutations). CRC patients with negative expressions of IGF-IR and COX-2 had significantly higher accumulative survival rate and longer mean survival duration than those with positive expressions of IGF-IR and COX-2. These findings indicate that IGF-1R and COX-2 expressions may be associated with Ras and BRAF genetic mutations, clinicopathological feature and prognosis of CRC patients.

Phase II trial of preoperative chemoradiation plus perioperative SOX chemotherapy in patients with locally advanced gastric cancer.

BACKGROUND AND PURPOSE: The ideal treatment strategy of patients with locally advanced gastric adenocarcinoma is unclear. The aim of this study is to evaluate the efficacy and feasibility of preoperative chemoradiation in these patients. PATIENTS AND METHODS: All patients underwent laparoscopic exploration or exploratory laparotomy before chemoradiation. Patients received one cycle of S-1 and oxalipatin followed by concurrent radiation and chemotherapy, then underwent another cycle of S-1 and oxalipatin. Surgery was performed 6-8 weeks after completing radiochemotherapy. The rate of curative gastrectomy and survival were investigated. This trial was registered with ClinicalTrial.gov, number NCT02024217. RESULTS: From April 2012 to August 2014, 40 patients were enrolled in the trial, and 36 patients were assessable. The most common hematologic toxic effects were leukopenia (80.6%), neutropenia (69.4%), and thrombocytopenia (50%); the most common nonhematologic toxic effects were anorexia (50%), nausea (22.3%), and vomiting (13.9%). There were no treatment related deaths. A total of 33 patients underwent second exploratory laparotomy after preoperative chemoradiation, and 24 (67%) patients received curative gastrectomy. The rates of pathological complete response (pCR) were 13.9%. The medial survival time (MST) was 30.3 months. CONCLUSION: Preoperative chemoradiation may be an effective treatment strategy among patients with locally advanced gastric adenocarcinoma.