Exploring the optimal indicator of short-term peridiagnosis weight dynamics to predict cancer survival: A multicentre cohort study.

BACKGROUND: Body weight and its changes have been associated with cancer outcomes. However, the associations of short-term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short-term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. METHODS: This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height-adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight-related indicators and compared their prognostic performance using Harrell's C-index, integrated discrimination improvement, continuous net reclassification improvement and time-dependent C-index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan-Meier analysis and multivariable-adjusted Cox regression models. RESULTS: The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow-up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C-index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P < 0.05). Time-dependent C-index analysis also indicated that peridiagnosis RWC was optimal for predicting OS. The multivariable-adjusted RCS analysis revealed an N-shaped non-linear association between peridiagnosis RWC and OS (PRWC < 0.001, Pnon-linear < 0.001). Univariate survival analysis showed that the peridiagnosis RWC groups could represent distinct mortality risk stratifications (P < 0.001). Multivariable survival analysis showed that, compared with the maintenance group (weight change < 5%), the significant (gain >10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5-10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5-10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. CONCLUSIONS: The prognostic performance of peridiagnosis RWC is superior to other weight-related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change-related premature deaths.

Precise visualization and ROS-dependent photodynamic therapy of colorectal cancer with a novel mitochondrial viscosity photosensitive fluorescent probe.

BACKGROUND: Colorectal cancer (CRC) is a prominent global cancer with high mortality rates among human beings. Efficient diagnosis and treatment have always been a challenge for CRC management. Fluorescence guided cancer therapy, which combines diagnosis with therapy into one platform, has brought a new chance for achieving precise cancer theranostics. Among this, photosensitizers, applied in photodynamic therapy (PDT), given the integration of real-time imaging capacity and efficacious treatment feasibility, show great potential to serve as remarkable tools. Although much effort has been put into constructing photosensitizers for locating and destroying CRC cells, it is still in high need to develop novel photosensitizers to attain specific detection and fulfil effective therapy. METHODS: Probe HTI was rational synthesized for the diagnosis and treatment of CRC. Spectrometric determination was carried out first, followed by the 1O2 generation ability test. Then, HTI was displayed in distinguishing CRC cells from normal cells Further, the PDT effect of the photosensitizer was studied in vitro. Additionally, HTI was used in CRC BALB/c nude mice model to validate its viscosity labelling and tumor suppression characteristics. RESULTS: We successfully fabricated a mitochondrial targeting probe, HTI, together with remarkable viscosity sensitivity, ultralow background interference, and excellent 1O2 generation capacity. HTI was favorably applied to the viscosity detection, displaying a 11-fold fluorescent intensity enhancement in solvents from 1.57 cp to 2043 cp. Then, it was demonstrated that HTI could distinguish CRC cells from normal cells upon the difference in mitochondrial viscosity. Moreover, HTI was qualified for producing 1O2 with high efficiency in cells, supported by the sparkling signals of DCFH after incubation with HTI under light irradiation. More importantly, the viscosity labelling and tumor suppression performance in CRC CDX model was determined, enriching the multifunctional validation of HTI in vivo. CONCLUSIONS: In this study, HTI was demonstrated to show a sensitive response to mitochondrial viscosity and possess a high 1O2 generation capacity. Both in vitro cell imaging and in vivo tumor treatment trials proved that HTI was effectively served as a robust scaffold for tumor labeling and CRC cells clearance. This breakthrough discovery held immense potential for advancing the early diagnosis and management of CRC through PDT. By leveraging HTI's properties, medical professionals could benefit from improved diagnostic accuracy and targeted treatment in CRC management, ultimately leading to enhanced patient outcomes.

FLOT1 promotes gastric cancer progression and metastasis through BCAR1/ERK signaling.

Flotillin-1 (FLOT1) is a member of the flotillin family and serves as a hallmark of lipid rafts involved in the process of signaling transduction and vesicular trafficking. Here, we find FLOT1 promotes gastric cancer cell progression and metastasis by interacting with BCAR1, through ERK signaling. FLOT1 regulates BCAR1 phosphorylation and translocation. Overexpression of FLOT1 increases, while knockdown of FLOT1 decreases gastric cancer cell proliferation, migration and invasion. BCAR1 knockdown could block FLOT1 induced gastric cancer cell proliferation, migration and invasion. Re-expression of wildtype rather than mutant BCAR1 (Y410F) could partially restore FLOT1 knockdown induced gastric cancer cell migration and invasion, while the restore could be inhibited by ERK inhibitor. Furthermore, FLOT1 and BCAR1 expression is closely related to gastric cancer patients' poor outcome. Thus, our findings confirm that BCAR1 mediates FLOT1 induced gastric cancer progression and metastasis through ERK signaling, which may provide a novel pathway for gastric cancer treatment.

Caprini risk assessment model combined with D-dimer to predict the occurrence of deep vein thrombosis and guide intervention after laparoscopic radical resection of colorectal cancer.

BACKGROUND: To explore the diagnostic value of Caprini risk assessment model (2005) combined with D-dimer for deep vein thrombosis, and to exclude patients with low incidence of thrombosis who might not need anticoagulation after surgery. METHODS: A total of 171 colorectal cancer patients who underwent surgery from January 2022 to August 2022 were enrolled in this study. Caprini risk assessment model was used to evaluate patients the day before surgery, and full-length venous ultrasonography of lower extremity was used to assess whether patients had thrombosis one day before surgery and the sixth day after surgery. The value of D-dimer was measured by enzyme-linked immunosorbent assays on the first day after surgery, and clinical data of patients were collected during hospitalization. RESULTS: A total of 171 patients were divided into IPC Group and IPC + LMWH Group according to whether low molecular weight heparin (LMWH) were used to prevent thrombus after surgery. Eventually, 17.6% (15/85) patients in IPC Group and 7% (6/86) patients in IPC + LMWH Group developed DVT. Through separate analysis of IPC Group, it is found that Caprini score and D-dimer were independent risk factors for DVT (Caprini OR 3.39 [95% CI 1.38-8.32]; P = 0.008, D-Dimer OR 6.142 [95% CI 1.209-31.187]; P = 0.029). The area under ROC curve of Caprini risk assessment model is 0.792 (95% CI 0.69-0.945, P < 0.01), the cut-off value is 9.5, and the area under ROC curve of D-dimer is 0.738 (95%CI 0.555-0.921, P < 0.01), the cut-off value is 0.835 µg/mL, and the area under the ROC curve was 0.865 (95% CI 0.754-0.976, P < 0.01) when both of them were combined. Based on decision curve analysis, it is found that Caprini risk assessment model combined with D-dimer can benefit patients more. All patients are divided into four groups. When Caprini score < 10 and D-dimer < 0.835 µg/mL, only 1.23% (1/81) of patients have thrombosis and LMWH has little significance. When Caprini score > 10 and D-dimer > 0.835 µg/mL, the incidence of DVT is 38.7% (12/31) and LMWH should be considered. CONCLUSIONS: The Caprini risk assessment model and D-dimer can provide more accurate risk stratification for patients after laparoscopic radical resection of colorectal cancer.

Excessive bowel volume loss during anus-preserving surgery for rectal cancer affects the bowel function after operation: A prospective observational cohort study (Bas-1611).

Background: Bowel volume loss during anus-preserving surgery (APS) may result in low anterior resection syndrome (LARS). We conducted this prospective observational cohort study to measure the incidence of LARS after surgery and evaluate the relationship between bowel volume loss and bowel function. Methods: Patients with R0 resectable rectal cancer who consented to several bowel function surveys through telephone interviews after the operation were included. Enrolled patients underwent standard APS for rectal cancer, and three length indexes, viz. length of excised bowel, length of the distal margin and length of the proximal margin (LPM) of fresh bowel specimens, were measured in vitro. Results: The three measured variables of the specimens showed a positively skewed distribution. Patient interviews revealed a trend of gradual improvement in bowel function. Univariate analyses revealed that longer LPM was associated with a significantly negative impact on bowel function at all time points. In multivariate analysis, LPM was found to be a significant risk factorstatistically significant, but its impact was not as strong as that of radiotherapy and low-middle tumour. Furthermore, there was no significant difference in the lymph node detection rate between <10-cm and ≥10-cm LPM groups. Conclusion: In APS for rectal cancer, bowel volume loss is an important factor causing postoperative bowel dysfunction. Controlling LPM to <10 cm may help improve postoperative bowel function.

Comparison of the performance of the GLIM criteria, PG-SGA and mPG-SGA in diagnosing malnutrition and predicting survival among lung cancer patients: A multicenter study.

BACKGROUND & AIMS: The present study aimed to compare the ability of the GLIM criteria, PG-SGA and mPG-SGA to diagnose malnutrition and predict survival among Chinese lung cancer (LC) patients. METHODS: This was a secondary analysis of a multicenter, prospective, nationwide cohort study, 6697 LC inpatients were enrolled between July 2013 and June 2020. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC), and quadratic weighted Kappa coefficients were calculated to compare the ability to diagnose malnutrition. There were 754 patients who underwent follow-up for a median duration of 4.5 years. The associations between the nutritional status and survival were analyzed by the Kaplan-Meier method and multivariable Cox proportional hazard regression models. RESULTS: The median age of LC patients was 60 (53, 66), and 4456 (66.5%) were male. There were 617 (9.2%), 752 (11.2%), 1866 (27.9%), and 3462 (51.7%) patients with clinical stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ LC, respectively. Malnutrition was present in 36.1%-54.2% (as evaluated using different tools). Compared with the PG-SGA (used as the diagnostic reference), the sensitivity of the mPG-SGA and GLIM was 93.7% and 48.3%; the specificity was 99.8% and 78.4%; and the AUC was 0.989 and 0.633 (P < 0.001). The weighted Kappa coefficients were 0.41 for the PG-SGA vs. GLIM, 0.44 for the mPG-SGA vs. GLIM, and 0.94 for the mPG-SGA vs PG-SGA in patients with stage Ⅰ-Ⅱ LC. These values were respectively 0.38, 0.39, and 0.93 in patients with stage Ⅲ-Ⅳ of LC. In a multivariable Cox analysis, the mPG-SGA (HR = 1.661, 95%CI = 1.348-2.046, P < 0.001), PG-SGA (HR = 1.701, 95%CI = 1.379-2.097, P < 0.001) and GLIM (HR = 1.657, 95%CI = 1.347-2.038, P < 0.001) showed similar death hazard ratios. CONCLUSIONS: The mPG-SGA provides nearly equivalent power to predict the survival of LC patients as the PG-SGA and the GLIM, indicating that all three tools are applicable for LC patients. The mPG-SGA has the potential to be an alternative replacement for quick nutritional assessment among LC patients.

Flotillin-1 is a prognostic biomarker for glioblastoma and promotes cancer development through enhancing invasion and altering tumour microenvironment.

Flotillin-1(FLOT1) has long been recognized as a tumour-promoting gene in several types of cancer. However, the expression and function of FLOT1 in glioblastomas (GBM) has not been elucidated. Here, in this study, we find that the expression level of FLOT1 in GBM tissue was much higher than that in normal brain, and the expression was even higher in the more aggressive subtypes and IDH status of glioma. Kaplan-Meier survival revealed that high FLOT1 expression is closely associated with poor outcome in GBM patients. FLOT1 knockdown markedly reduced the proliferation, migration and invasiveness of GBM cells, while FLOT1 overexpression significantly increases GBM cell proliferation, migration and invasiveness. Mechanistically, FLOT1 expression may play a potential role in the microenvironment of GBM. Therefore, FLOT1 promotes GBM proliferation and invasion in vitro and in vivo and may serve as a biomarker of prognosis and therapeutic potential in the fight against GBM.

Impact of Salvage Surgery following Colonic Endoscopic Polypectomy for Patients with Invasive Neoplasia.

BACKGROUND: Invasive neoplasia (Tis-T1) are increasingly being encountered in the daily routine of endoscopic polypectomy. However, the need for salvage surgery following endoscopic therapy for invasive neoplasia is controversially discussed. PATIENTS AND METHODS: Patients with endoscopic removal of invasive neoplasia were identified from the national Surveillance Epidemiology and End Results (SEER) Database 2005 to 2015. Survival analysis and Cox proportional hazard regression analysis in cancer-specific mortality and overall survival rate was used, which were stratified by T stage and polyp size. RESULTS: A total of 5805 patients with endoscopic removal of invasive neoplasia were included in the analysis, of whom 1214 (20.9%) underwent endoscopic treatment alone and 4591 (79.1%) underwent endoscopic resection plus surgery. The survival analysis revealed that patients undergoing salvage surgery had a significantly better cancer-specific survival (97.4% vs. 95.8%, p-value = 0.017). In patients with T1 stage, additional salvage surgery led to a significantly higher cancer-specific survival (92.1% vs. 95.0%, p value = 0.047). CONCLUSION: Salvage surgery following endoscopic polypectomy may improve the oncological survival of patients with invasive neoplasia, especially in patients with T1 stage. Furthermore, the T stage, size, and localization of polyps, as well as the level of CEA, could be identified as significant predictors for lymphonodal and distant metastases.

Choosing Kinase Inhibitors for Androgen Deprivation Therapy-Resistant Prostate Cancer.

Androgen deprivation therapy (ADT) is a systemic therapy for advanced prostate cancer (PCa). Although most patients initially respond to ADT, almost all cancers eventually develop castration resistance. Castration-resistant PCa (CRPC) is associated with a very poor prognosis, and the treatment of which is a serious clinical challenge. Accumulating evidence suggests that abnormal expression and activation of various kinases are associated with the emergence and maintenance of CRPC. Many efforts have been made to develop small molecule inhibitors to target the key kinases in CRPC. These inhibitors are designed to suppress the kinase activity or interrupt kinase-mediated signal pathways that are associated with PCa androgen-independent (AI) growth and CRPC development. In this review, we briefly summarize the roles of the kinases that are abnormally expressed and/or activated in CRPC and the recent advances in the development of small molecule inhibitors that target kinases for the treatment of CRPC.

A Six-microRNA Signature Nomogram for Preoperative Prediction of Tumor Deposits in Colorectal Cancer.

PURPOSE: Tumor deposits (TDs) are acknowledged negative prognostic factors in colorectal cancer (CRC), and their pathogenesis remains a puzzle. This study aimed to construct and validate a nomogram available for preoperative TDs prediction in CRC patients. PATIENTS AND METHODS: Patients from the Surveillance, Epidemiology, and End Results (SEER) and the cancer genome atlas (TCGA) databases were randomly divided into training and validation sets according to the sample size ratio of 7:3. Univariate logistic regression was performed for identifying differentially expressed microRNAs between TDs and non-TDs. Nomograms for TDs prediction were developed from the multivariate logistic regression model with least absolute shrinkage and selection operator and were validated internally in terms of accuracy, calibration, and clinical utility. Based on the target genes, pathways tightly associated with TDs were selected using enrichment analysis. RESULTS: Six clinicopathologic factors and expressions of six microRNAs (miR-614, miR-1197, miR-4770, miR-3136, miR-3173, and miR-4636) differed significantly between TDs and non-TDs CRC patients from the SEER and TCGA training sets. We compared potential prediction discrimination between two nomograms: a clinicopathologic nomogram and a six-microRNA signature nomogram. The six-microRNA signature nomogram revealed better accuracy than the clinicopathologic one for TDs prediction (AUC values of 0.96 and 0.93 in the validation cohort). The calibration plots and decision curve analysis demonstrated that the six-microRNA signature nomogram had better validity and a greater prognostic benefit versus the clinicopathologic one for TDs prediction. Calcium signaling pathways were closely associated with roles of the six microRNAs in TDs of CRC patients. CONCLUSION: The six-microRNA signature nomogram can be used as an efficient tool for preoperative TDs prediction in CRC patients.

ATF4/TXNIP/REDD1/mTOR signaling mediates the antitumor activities of liver X receptor in pancreatic cancers.

Background: Limited by difficulties in early detection and availabilities of effective treatments, pancreatic cancer is a highly malignant disease with poor prognosis. Nuclear receptors are a family of ligand-dependent transcription factors that are highly druggable therapeutic targets playing critical roles in human physiological and pathological development, including cancer. In this study, we explored the therapeutic potential as well as the molecular mechanisms of liver X receptor (LXR) agonist GW3965 in pancreatic cancer. Methods: Soft-agar colony formation assay, xenograft tumors, Oligonucleotide microarray, Reverse transcription real-time polymerase chain reaction, Western immunoblotting and Immunohistochemistry were used in this study. Results: We demonstrated pleotropic in vitro activities of GW3965 in pancreatic cell lines MIA PaCa-2 and BXPC3 including reduction of cell viability, inhibition of cell proliferation, stimulation of cell death, and suppression of colony formation, which translated to significant inhibition of xenograft tumor growth in vitro. By mapping the gene expression profiles, we identified the up-regulations of 188 and the down-regulations of 92 genes common to both cell lines following GW3965 treatment. Genes responsive to GW3965 represent a variety of biological pathways vital for multiple cellular functions. Specifically, we identified that the activating transcription factor 4/thioredoxin-interacting protein/regulated in development and DNA damage responses 1/mechanistic target of rapamycin (ATF4/TXNIP/REDD1/mTOR) signaling critically controls GW3965-mediated regulation of cell proliferation/death. The significance of the ATF4/TXNIP/REDD1/mTOR pathway was further supported by associated expressions in xenograft tumors as well as human pancreatic cancer samples. Conclusions: This study provides the pre-clinical evidence that LXR agonist is a promising therapy for pancreatic cancer.

Thermal reduction-desorption of cadmium from contaminated soil by a biomass co-pyrolysis process.

Thermal desorption is one of the methods commonly used for the remediation of contaminated soil. However, its suitability for the treatment of widespread Cd-contaminated soil was seldom investigated, because the desorption of Cd was found to be difficult, even at a high heating temperature. In the present study, a biomass co-pyrolysis (BCP) method is proposed for the thermal treatment of Cd-contaminated soil. The results showed that, when the mixture of biomass and contaminated soil was pyrolyzed at ~550 oC, the gaseous pyrolytic products (such as CO and hydrocarbon gases) from the biomass could chemically reduce the Cd(II) into volatile Cd0, thereby allowing the evaporation of vaporized Cd0 from the soil within a short operating time. The BCP method can achieve a highly efficient removal of Cd from the soil samples spiked with a large amount of Cd(II). The remediated soil, containing the remaining biochars, showed a good regreening potential and a significant decrease in Cd bioavailability. It also showed a good performance for the remediation of field soils from four contaminated sites (>92% removal efficiencies), and one of the treated soils could even meet the Cd screening level of agricultural land of China.

Case report: Neurofibromatosis type 1 gastrointestinal stromal tumor and small bowel adenocarcinoma with a novel germline NF1 frameshift mutation.

A synchronous case of small bowel adenocarcinoma(SAB) is reported, accompanied with gastrointestinal stromal tumor(GIST),and gangliocytomain in an elderly woman with neurofibromatosis type 1 (NF-1). A 67-year-old female was hospitalized with the chief complaint of abdominal pain, the computed tomography scan indicated a large bowel mass. Multiple tumors were found in the small intestine, through which two larger tumors (7 cm and 1.5 cm) were resected. A novel germline NF1 mutation and a PMS2 mutation were identified after genetic testing, followed by the exploration of possible relationship between them in promoting tumorigenesis. Our results suggest multiple gastrointestinal tumors emerging in NF1 patients, and genetic testing can better guide postoperative treatment in a more efficient way.

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance.

Although castration-resistant prostate cancer (CRPC) as a whole, by its name, refers to the tumors that relapse and/or regrow independently of androgen after androgen deprivation therapy (ADT), untreated tumor, even in early-stage primary prostate cancer (PCa), contains androgen-independent (AI) PCa cells. The transformation of androgen-dependent (AD) PCa to AI PCa under ADT is a forced evolutionary process, in which the small group of AI PCa cells that exist in primary tumors has the unique opportunity to proliferate and expand selectively and dominantly, while some AD PCa cells that have escaped from ADT-induced death acquire the capability to survive in an androgen-depleted environment. The adaptation and reprogramming of both PCa cells and the tumor microenvironment (TME) under ADT make PCa much stronger than primary tumors so that, currently, there are no effective therapeutic methods available for the treatment of CRPC. Many mechanisms have been found to be related to the emergence and maintenance of PCa castration resistance; in this review, we focus on the role of inflammatory signaling in both PCa cells and the TME for the emergence and maintenance of CRPC and summarize the recent advances of therapeutic strategies that target inflammatory signaling for the treatment of CRPC.

Comprehensive analysis of lncRNA-miRNA-mRNA regulatory networks for microbiota-mediated colorectal cancer associated with immune cell infiltration.

Recent findings have identified microbiota as crucial participants in many disease conditions, including cancers. Competing endogenous RNA (ceRNA) is regarded as a candidate mechanism involving relevant biological processes. We therefore constructed a ceRNA network using the TCGA and GEO database, to determine the potential mechanisms of microbiota-mediated colorectal carcinogenesis and progression. We found a total of 75 lncRNAs, 8 miRNAs, and 9 mRNAs in the probiotics-mediated ceRNA network and a total of 49 lncRNAs, 4 miRNAs, and 3 mRNA in the pathobiont-mediated ceRNA network, which could induce the microbiota-mediated carcinogenesis and progression. The GO and KEGG analysis indicated that the ceRNA network is mainly enriched in the metabolic process, and two unique pathways (the p53 signaling pathway and microRNA in cancer), respectively. A four-gene signature (FRMD6-AS2, DIRC3, LIFR-AS1, and MRPL23-AS1) was suggested as an independent prognostic factor. Four lncRNAs (LINC00355, KCNQ1OT1, LINC00491, and HOTAIR) were associated with poor survival. Three small molecule candidate anticancer drugs (Pentoxyverine, Rimexolone, and Doxylamine) were identified. A four-gene signature (FAM129A, BCL2, PMAIP1, and RPS6) is significantly correlated with immune infiltration level. This study provides a promising biomarker reservoir to explore the mechanism by which microbiota regulate the ceRNA network involving the immune response, and further participate in colorectal carcinogenesis and progression.

Nuclear IGF1R interacts with NuMA and regulates 53BP1­dependent DNA double­strand break repair in colorectal cancer.

Nuclear insulin­like growth factor 1 receptor (nIGF1R) has been associated with poor overall survival and chemotherapy resistance in various types of cancer; however, the underlying mechanism remains unclear. In the present study, immunoprecipitation­coupled mass spectrometry was performed in an IGF1R­overexpressing SW480­OE colorectal cancer cell line to identify the nIGF1R interactome. Network analysis revealed 197 proteins of interest which were involved in several biological pathways, including RNA processing, DNA double­strand break (DSB) repair and SUMOylation pathways. Nuclear mitotic apparatus protein (NuMA) was identified as one of nIGF1R's colocalizing partners. Proximity ligation assay (PLA) revealed different levels of p53­binding protein 1 (53BP1)­NuMA colocalization between IGF1R­positive (R+) and IGF1R­negative (R­) mouse embryonic fibroblasts following exposure to ionizing radiation (IR). 53BP1 was retained by NuMA in the R­ cells during IR­induced DNA damage. By contrast, the level of NuMA­53BP1 was markedly lower in R+ cells compared with R­ cells. The present data suggested a regulatory role of nIGF1R in 53BP1­dependent DSB repair through its interaction with NuMA. Bright­field PLA analysis on a paraffin­embedded tissue microarray from patients with colorectal cancer revealed a significant association between increased nuclear colocalizing signals of NuMA­53BP1 and a shorter overall survival. These results indicate that nIGF1R plays a role in facilitating 53BP1­dependent DDR by regulating the NuMA­53BP1 interaction, which in turn might affect the clinical outcome of patients with colorectal cancer.

EphA2-YES1-ANXA2 pathway promotes gastric cancer progression and metastasis.

Erythropoietin-producing hepatocellular receptor A2 (EphA2) is a key member of the receptor tyrosine kinase (RTK) family, while YES Proto-Oncogene 1 (YES1) is a non-receptor tyrosine kinase (nRTK) and annexin A2 (ANXA2) belongs to the calcium-dependent phospholipid-binding protein family annexins. Here, we show that EphA2, YES1, and ANXA2 form a signal axis, in which YES1 activated by EphA2 phosphorylates ANXA2 at Tyr24 site, leading to ANXA2 activation and increased ANXA2 nuclear distribution in gastric cancer (GC) cells. Overexpression (OE) of YES1 increases, while knockdown (KD) of YES1 or ANXA2 decreases GC cell invasion and migration in vitro and tumor growth in mouse models. Reexpression of wildtype (WT) rather than mutant ANXA2 (Tyr24F) in ANXA2 knockdown (ANXA2-KD) GC cells restores YES1-induced cell invasion and migration, while neither WT nor mutant ANXA2 (Tyr24F) can restore cell invasion and migration in YES1-KD GC cells. In addition, the activation of EphA2-YES1-ANXA2 pathway is correlated with poor prognosis. Thus, our results establish EphA2-YES1-ANXA2 axis as a novel pathway that drives GC invasion and metastasis, targeting this pathway would be an efficient way for the treatment of GC.

Magnetic endoscopic imaging as a rational investment for specific colonoscopies: a systematic review and meta-analysis.

BACKGROUND: Magnetic endoscopic imaging (MEI) was regarded as an adjuvant device to improve procedural efficacy and patients' comfort during colonoscopy. METHODS: Several electronic databases were searched to identify eligible studies. Based on the heterogeneity of included studies, random-effects or fixed-effects models were used to calculate pooled risk ratios (RR), risk difference (RD) or mean difference (MD) along with 95% confidence intervals (CIs). RESULTS: Twenty-one randomized controlled trials (RCTs) were selected for meta-analysis, with a total of 7,060 patients. Although there is a slightly lower risk of cecal intubation failure with the adjuvant of MEI (RD 3%; P < 0.00001) compared to the control group, the updated studies show no significant benefits. Similarly, the cecal intubation time, pain scores, and loop formation with the adjuvant of MEI did not show any advantages. However, considerable significant benefits were found in the subgroup of technically difficult colonoscopy and inexperienced colonoscopists. Moreover, MEI was associated with lower loop intubation time, lower abdominal compression times, and better lesion localization. CONCLUSION: The clinical benefits of MEI could be exaggerated. However, MEI has considerable advantages in technically difficult colonoscopies, the assistance for inexperienced colonoscopists, loop resolving, and lesion localization.