T2WI-based MRI radiomics for the prediction of preoperative extranodal extension and prognosis in resectable rectal cancer.

OBJECTIVE: To investigate whether T2-weighted imaging (T2WI)-based intratumoral and peritumoral radiomics can predict extranodal extension (ENE) and prognosis in patients with resectable rectal cancer. METHODS: One hundred sixty-seven patients with resectable rectal cancer including T3T4N + cases were prospectively included. Radiomics features were extracted from intratumoral, peritumoral 3 mm, and peritumoral-mesorectal fat on T2WI images. Least absolute shrinkage and selection operator regression were used for feature selection. A radiomics signature score (Radscore) was built with logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each Radscore. A clinical-radiomics nomogram was constructed by the most predictive radiomics signature and clinical risk factors. A prognostic model was constructed by Cox regression analysis to identify 3-year recurrence-free survival (RFS). RESULTS: Age, cT stage, and lymph node-irregular border and/or adjacent fat invasion were identified as independent clinical risk factors to construct a clinical model. The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and independent clinical risk factors achieved a better AUC than the clinical model in the training (0.799 vs. 0.736) and validation cohorts (0.723 vs. 0.667). Nomogram-based ENE (hazard ratio [HR] = 2.625, 95% CI = 1.233-5.586, p = 0.012) and extramural vascular invasion (EMVI) (HR = 2.523, 95% CI = 1.247-5.106, p = 0.010) were independent risk factors for predicting 3-year RFS. The prognostic model constructed by these two indicators showed good performance for predicting 3-year RFS in the training (AUC = 0.761) and validation cohorts (AUC = 0.710). CONCLUSION: The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and clinical risk factors could predict preoperative ENE. Combining nomogram-based ENE and MRI-reported EMVI may be useful in predicting 3-year RFS. CRITICAL RELEVANCE STATEMENT: A clinical-radiomics nomogram could help preoperative predict ENE, and a prognostic model constructed by the nomogram-based ENE and MRI-reported EMVI could predict 3-year RFS in patients with resectable rectal cancer. KEY POINTS: • Intratumoral and peritumoral 3 mm Radscore showed the most capability for predicting ENE. • Clinical-radiomics nomogram achieved the best predictive performance for predicting ENE. • Combining clinical-radiomics based-ENE and EMVI showed good performance for 3-year RFS.

Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China.

BACKGROUND: Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. METHODS: This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. RESULTS: Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. CONCLUSION: In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.

Incidence, prevention, risk factors, and prediction of venous thromboembolism in Chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.

MRI-based multiregional radiomics for preoperative prediction of tumor deposit and prognosis in resectable rectal cancer: a bicenter study.

OBJECTIVE: To build T2WI-based multiregional radiomics for predicting tumor deposit (TD) and prognosis in patients with resectable rectal cancer. MATERIALS AND METHODS: A total of 208 patients with pathologically confirmed rectal cancer from two hospitals were prospectively enrolled. Intra- and peritumoral features were extracted separately from T2WI images and the least absolute shrinkage and selection operator was used to screen the most valuable radiomics features. Clinical-radiomics nomogram was developed by radiomics signatures and the most predictive clinical parameters. Prognostic model for 3-year recurrence-free survival (RFS) was constructed using univariate and multivariate Cox analysis. RESULTS: For TD, the area under the receiver operating characteristic curve (AUC) for intratumoral radiomics model was 0.956, 0.823, and 0.860 in the training cohort, test cohort, and external validation cohort, respectively. AUC for the peritumoral radiomics model was 0.929, 0.906, and 0.773 in the training cohort, test cohort, and external validation cohort, respectively. The AUC for combined intra- and peritumoral radiomics model was 0.976, 0.918, and 0.874 in the training cohort, test cohort, and external validation cohort, respectively. The AUC for clinical-radiomics nomogram was 0.989, 0.777, and 0.870 in the training cohort, test cohort, and external validation cohort, respectively. The prognostic model constructed by combining intra- and peritumoral radiomics signature score (radscore)-based TD and MRI-reported lymph nodes metastasis (LNM) indicated good performance for predicting 3-year RFS, with AUC of 0.824, 0.865, and 0.738 in the training cohort, test cohort and external validation cohort, respectively. CONCLUSION: Combined intra- and peritumoral radiomics model showed good performance for predicting TD. Combining intra- and peritumoral radscore-based TD and MRI-reported LNM indicated the recurrence risk. CLINICAL RELEVANCE STATEMENT: Combined intra- and peritumoral radiomics model could help accurately predict tumor deposits. Combining this predictive model-based tumor deposits with MRI-reported lymph node metastasis was associated with relapse risk of rectal cancer after surgery. KEY POINTS: • Combined intra- and peritumoral radiomics model provided better diagnostic performance than that of intratumoral and peritumoral radiomics model alone for predicting TD in rectal cancer. • The predictive performance of the clinical-radiomics nomogram was not improved compared with the combined intra- and peritumoral radiomics model for predicting TD. • The prognostic model constructed by combining intra- and peritumoral radscore-based TD and MRI-reported LNM showed good performance for assessing 3-year RFS.

The application of apparent diffusion coefficients derived from intratumoral and peritumoral zones for assessing pathologic prognostic factors in rectal cancer.

OBJECTIVE: To investigate the diagnostic performance of the apparent diffusion coefficient (ADC) derived from intratumoral and peritumoral zones for assessing pathologic prognostic factors in rectal cancer. MATERIALS AND METHODS: One hundred forty-six patients with rectal cancer who underwent preoperative MRI were prospectively enrolled. Two radiologists independently placed free-hand regions of interest (ROIs) in the largest tumor cross section and three small ROIs on the peritumoral zone adjacent to the tumor contour. Maximum values of tumor ADC (ADCtmax), minimum values of tumor ADC (ADCtmin), mean values of tumor ADC (ADCtmean), mean values of peritumor ADC (ADCpmean), and ADCpmean/ADCtmean (ADC ratio) were obtained on ADC maps and correlated with prognostic factors using uni- and multivariate logistic regression, and receiver operating characteristic curve (ROC) analysis. RESULTS: Interobserver agreement was excellent for ADCtmax and ADCtmean (intraclass correlation coefficient [ICC], 0.915-0.958), and were good for ADCtmin, ADCpmean, and ADC ratio (ICC, 0.774-0.878). The ADC ratio was significantly higher in the poor differentiation, T3-4 stage, lymph node metastasis (LNM)-positive, extranodal extension (ENE)-positive, tumor deposit (TD)-positive, and lymphovascular invasion (LVI)-positive groups than that in the well-moderate differentiation, T1-2 stage, LNM-negative, ENE-negative, TD-negative, and LVI-negative groups (p = 0.008, < 0.001, < 0.001, 0.001, < 0.001, and < 0.001, respectively). The area under the ROC curve (AUC) of the ADC ratio was the highest for assessing poor differentiation (0.700), T3-4 stage (0.707), LNM-positive (0.776), TD-positive (0.848), and LVI-positive (0.778). Both the ADC ratio (AUC = 0.677) and ADCpmean (AUC = 0.686) showed higher diagnostic performance for assessing ENE. CONCLUSION: The ADC ratio could provide better predictive performance for assessing preoperative prognostic factors in resectable rectal cancer. KEY POINTS: • Both the peritumor/tumor ADC ratio and ADCpmean are correlated with important prognostic factors of resectable rectal cancer. • Both peritumor ADC and peritumor/tumor ADC ratio had higher diagnostic performance than tumor ADC for assessment of prognostic factors in resectable rectal cancer. • Peritumor/tumor ADC ratio showed the most capability for the assessment of prognostic factors in resectable rectal cancer.

Value of intravoxel incoherent motion for assessment of lymph node status and tumor response after chemoradiation therapy in locally advanced rectal cancer.

OBJECTIVE: To assess the role of region of interest (ROI) selection of intravoxel incoherent motion (IVIM) for predicting lymph node metastases (LNM) and tumor response after chemoradiation therapy (CRT) in locally advanced rectal cancer. MATERIALS AND METHODS: Seventy-nine patients with biopsy-proven rectal adenocarcinoma who underwent pre- and post-CRT MRI and surgery were prospectively enrolled. The exclusion criteria included nonresectable and/or metastatic disease and loss of follow-up. Pathological stage was determined using ypTNM stage and tumor regression grade. Slow diffusion coefficient (D), fast diffusion coefficient (D*), perfusion-related diffusion fraction (f), apparent diffusion coefficient (ADC) and their percentage changes (Δ%) were evaluated by two readers using whole-volume, single-slice and small samples ROI methods. Risk factors including carcinoembryonic antigen, post-CRT T-staging, extramural venous invasion and IVIM parameters were evaluated through multivariate analyses. Areas under the receiver operating characteristic curves (AUCs) were calculated to evaluate diagnostic performance. Duration of follow-up was two-year. Recurrence-free survival of patients with LNM and tumor response was estimated using Kaplan-Meier analysis. RESULTS: Interobserver agreement were good for pre- and post-CRT three ROI methods (intraclass correlation coefficient [ICC], 0.581-0.953). Whole-volume ROI-derived Δ%D was an independent risk factor for LNM, non-pathological complete response (non-pCR) and poor response (odds ratio, 0.940, 0.952, 0.805, respectively; all p < 0.001). Whole-volume ROI-derived Δ%D showed best AUC of 0.810, 0.851 and 0.903 for LNM, non-pCR and poor response (cutoff value, 31.8%, 54.5%, 52.8%, respectively). Patients with post-CRT LNM showed reduction in 2-year recurrence-free survival (hazard ratio, 3.253). CONCLUSIONS: Whole-volume ROI-derived Δ%D provided high diagnostic performance for evaluating post-CRT LNM and tumor response. Patients with post-CRT LNM showed earlier recurrence.

Identification of Key mRNAs and Pathways in Colorectal Cancer.

Colorectal cancer (CRC) is the third most cancer-related death worldwide. This work aimed to identify potential hub genes and dysregulated pathways in the CRC by bioinformatics analysis. Three gene expression datasets were collected from GEO datasets, including tumor sample (N = 242) and adjacent nontumor tissue sample (N = 59). RankProd was used to discover the differential expressed genes between tumor and adjacent nontumor tissues for datasets generated by different laboratories. The gene set enrichment analysis conducted on the DE genes, followed by the protein-protein interaction (PPI) network. In total, 2,007 significant differential expression (DE) genes between tumor and adjacent nontumor tissues, include 1,090 upregulated genes and 917 downregulated genes in the tumor. The DE mRNAs are involved in cancer-related pathways. We comprehensively identified the CRC-related key mRNAs. Our data demonstrated combined different resources of transcriptomes will promote the understanding of the molecular mechanisms underlying CRC development and may be useful in discovering candidate molecular biomarkers for diagnosing, prognosis, and treating of CRC.

Thymic carcinoma metastasize to the small intestine: a case report.

BACKGROUND: Thymic carcinoma is a rare mediastinal neoplasm with a high malignant potential. It often shows pleural invasion and distant metastasis. The metastasis of thymic carcinoma to the small intestine is rarely reported and difficult to distinguish from other gastrointestinal tract tumors. CASE PRESENTATION: An elderly man presented with lower abdominal pain for 2 months. Abdominal CT showed a mass communicated with the small intestinal lumen. After radical resection of the small intestinal tumor, resected specimens showed moderately differentiated squamous-cell carcinoma with lymph nodes metastases. The patient received chest CT and was found to have a mass in anterior mediastinum. Biopsies of the mass revealed thymic squamous-cell carcinoma. CONCLUSIONS: We highlighted the metastasis of thymic carcinoma to the small intestine is rare and easily misdiagnosed. In patients with a mass communicated with the small intestinal lumen, a suspicion of thymic carcinoma metastasis should not be overlooked and we should make accurate differential diagnosis from the other small intestinal tumors.

A pH-responsive Pickering Nanoemulsion for specified spatial delivery of Immune Checkpoint Inhibitor and Chemotherapy agent to Tumors.

Rationale: Immune checkpoint (ICP) blockade therapy combined with chemotherapy is a promising treatment strategy for tumors. Chemotherapeutic agents usually function inside the tumor cells, while ICP inhibitors are efficacious out of the tumor cells. It is desirable to effectively co-deliver an ICP inhibitor and a chemotherapy agent to different sites of a tumor. We have designed an effective drug delivery system to accomplish both objectives. Methods: We designed a Pickering nanoemulsion (PNE) using multi-sensitive nanogels with pH-responsive, hydrophilicity-hydrophobicity switch, and redox-responding properties as an oil/water interfacial stabilizer. The D/HY@PNE was employed for specified spatial delivery of the chemotherapy agent doxorubicin (DOX) and ICP inhibitor HY19991 (HY). We systematically investigated the pH-responsive disassembly of PNE, the release of DOX and HY from D/HY@PNE in the tumor microenvironment, enhanced tumor penetration of DOX, immunogenic cell death (ICD), antitumor efficacy, and the immune response induced by D/HY@PNE in vitro and in vivo. Results: D/HY@PNE disassembled to release the ICP inhibitor HY and DOX-loaded nanogels due to the hydrophilicity-hydrophobicity reversal of nanogels in the acidic tumor microenvironment. Quantitative analysis indicates that D/HY@PNE presents enhanced tumor penetration behavior and effectively induces ICD. The strong immune response induced by D/HY@PNE was due to the efficient synergetic combination of chemotherapy and immunotherapy and resulted in enhanced antitumor efficacy in 4T1 tumor-bearing mice. Conclusion: This novel strategy highlights the promising potential of a universal platform to co-deliver different therapeutic or diagnostic reagents with spatial regulation to improve the anti-tumor effect.

[Expression Level of FLRG in Colon Cancer Tissue and Its Clinical Significance].

OBJECTIVE: To investigate the expression of follistatin related gene ( FLRG) in colon cancer and its relationship with clinicopathological features of colon cancer. METHODS: The cancer tissue, paracancerous tissue and normal tissue were collected from 80 patients with colon cancer who underwent radical operation from December 2018 to December 2019. Immunohistochemistry and Real-time PCR were carried out to examine the expression of FLRG and the clinical implications of FLRG was further analyzed. RESULTS: The expression of FLRG in colon cancer tissues was significantly higher than that in paracancerous tissues and normal tissues ( P<0.05), and the expression of FLRG in paracancerous tissues was significantly higher than that in normal tissues ( P<0.05). There was no significant difference in the expression of FLRG among colon cancer patients with different sex, age, tumor growth location and differentiation degree ( P>0.05). The expression level of FLRG in patients with distant metastasis was higher than that in patients without distant metastasis ( P<0.05), and the expression level of FLRG in patients with late clinical stage (stage Ⅲ and Ⅳ) was higher than that in patients with earlier clinical stage (stage Ⅰ and Ⅱ) ( P<0.05). CONCLUSION: FLRG is up-regulated in colon cancer tissue, which may be involved in the regulation of tumor development. FLRG may be a potential prognostic target.

TRPV1 Induced Apoptosis of Colorectal Cancer Cells by Activating Calcineurin-NFAT2-p53 Signaling Pathway.

BACKGROUND/AIMS: TRPV1 is a nonselective Ca2+ channel which has recently been observed in many cancers, while its effect on cell proliferation, apoptosis, metabolism, and cancer development in colorectal cancer (CRC) is still unclear. In this study, we hypothesized that TRPV1 is a tumor suppressor in CRC development as well as the underlying mechanism. METHODS: Immunohistochemistry assay was applied to detect the expression of TRPV1 protein in CRC tissues. HCT116 cell proliferation and apoptosis were measured by CCK-8 and flow cytometry, respectively. Cellular Ca2+ concentration was measured by Fluo-4/AM-based flow cytometer. Apoptosis-related proteins were measured by Western blotting. RESULTS: In this study, we found that TRPV1 expression was significantly decreased in CRC tissues, compared with CRC-adjacent tissues and normal tissues, respectively. Then, we found that the TRVP1 agonist capsaicin treatment inhibited CRC growth and induced apoptosis by activating P53. Subsequent mechanistic study revealed that the TRPV1 induced cytosolic Ca2+ influx to regulate cell apoptosis and p53 activation through calcineurin. CONCLUSIONS: This study suggests that TRPV1 served as a tumor suppressor in CRC and contributed to the development of novel therapy of CRC.

Genome-Wide Network-Based Analysis of Colorectal Cancer Identifies Novel Prognostic Factors and an Integrative Prognostic Index.

BACKGROUND/AIMS: Colorectal cancer (CRC) is one of leading cancers in both incidence and mortality rate. The 5-year survival rate varies considerably depending on the pathological stage of the tumor. Although prominent progress has been made through screening for survival-associated factors from a certain type of genetic or epigenetic modifications, few attempts have been made to apply a network-based approach in prognostic factor identification, which could prove valuable for a complex, multi-faceted disease such as CRC. METHODS: In this study, a TCGA dataset of 379 CRC patients was subjected to a network-based analysis strategy consisting of multivariate regression, co-expression network and gene regulatory network analyses, and survival analyses. Both genetic and epigenetic aberrations, including those in gene expression and DNA methylation at specific sites, were screened for significant association with patient survival. A prognostic index (PI) integrating all potential prognostic factors was subsequently validated for its prognostic value. RESULTS: A collection of six miRNAs, eleven mRNAs, and nine DNA methylation sites were identified as potential prognostic factors. The low- and high-risk patient groups assigned based on PI level showed significant difference in overall survival (hazard ratio = 1.32, 95% confidence interval 1.29-1.36, p < 0.0001). Patients in the low- and high-risk groups can be further divided into a total of four subgroups, based on pathological staging. In the two high-risk subgroups (PI > 0), there was significant different (Cox p < 0.0001) in OS between the earlier (stages I/II) and later stages (stages III/IV). However, in the two low-risk subgroups (PI < 0), earlier (stages I/II) and later stages (stages III/IV) showed no significant difference in OS (Cox p = 0.185). On the other hand, there were significant differences in OS between the low- and high-risk subgroups when both subgroups were of earlier stages (Cox p < 0.001) or of later stages (Cox p < 0.0001). CONCLUSION: The novel network-based, integrative analysis adopted in this study was efficient in screening for prognostic predictors. Along with PI, the set of 6 miRNAs, 11 mRNAs, and 9 DNA methylation sites could serve as the basis for improved prognosis estimation for CRC patients in future clinical practice.

A novel APC mutation identified in a large Chinese family with familial adenomatous polyposis and a brief literature review.

Familial adenomatous polyposis (FAP), an autosomal dominant disease, is a colon cancer predisposition syndrome that manifests as a large number of adenomatous polyps. Mutations in the Adenomatous polyposis coli (APC) gene are responsible for the majority of cases of FAP. The purpose of the present study was to report the clinical features of a Chinese family with FAP and screen for novel mutations using the targeted next­generation sequencing technology. Among the 29 family members, 12 were diagnosed of FAP. Based on an established filtering strategy and data analyses, along with confirmation by Sanger sequencing and co­segregation, a novel frameshift mutation c.1317delA (p.Ala440LeufsTer14) in exon 10 of the APC gene was identified. To the best of our knowledge, this mutation has not been reported prior to the present study. In addition, it was correlated with extra­colonic phenotypes featuring duodenal polyposis and sebaceous cysts in this family. This novel frameshift mutation causing FAP not only expands the germline mutation spectrum of the APC gene in the Chinese population, but it also increases the understanding of the phenotypic and genotypic correlations of FAP, and may potentially lead to improved genetic counseling and specific treatment for families with FAP in the future.

Long non-coding RNA PlncRNA-1 promotes cell proliferation and hepatic metastasis in colorectal cancer.

Emerging evidence has identified that long non-coding RNAs (lncRNAs) may play an important role in the pathogenesis of many cancer types, including colorectal cancer (CRC). However, the role of PlncRNA-1 in CRC remains unclear. The aim of our present study was to investigate the potential functions of PlncRNA-1 in CRC and to identify the underlying mechanisms of action. We demonstrated that up-regulated PlncRNA-1 in CRC tissues and cells promoted cell proliferation by accelerating cell cycle process and inhibiting cell apoptosis in vitro, enhanced tumor growth and matastasis in vivo and was associated with cell migration and invasion, EMT process of CRC cells. In addition, PlncRNA-1 was a target of miR-204 and enhanced the expression of an endogenous miR-204 target, MMP9 in CRC cells. Furthermore, we found that PlncRNA-1 activates Wnt/ß-catenin pathway through the miR-204 in CRC cells. These results suggest that the PlncRNA-1/miR-204/ Wnt/ß-catenin regulatory network may shed light on tumorigenesis in CRC.

Nano-sized paramagnetic and fluorescent fluorinated carbon fiber with high NIR absorbance for cancer chemo-photothermal therapy.

Nano-sized fluorinated carbon fiber possesses unique charge distribution and special chemical bonds and holds great promise in biomedicine. However, its synthesis remains a big challenge on account of the chemical inertness and strong hydrophobicity of C-F bonds. Herein, an up-bottom method to prepare nano-sized and water-soluble fluorinated carbon fiber oxide (FCO) with tunable lengths and adjustable fluorine levels was first developed. It was found that the effective control over structure and composition endowed the FCO with high photoluminescence (PL) and near-infrared (NIR) light absorbance, which was further employed to monitor the drug loading by turn-off PL and treat cancer by photothermal therapy (PTT). We also reported the first experimental example of paramagnetic FCO, whose novel paramagnetism was generated by point defects from fluorine invasion. Moreover, the FCO was noncovalently functionalized with polyvinylpyrrolidone, loaded with doxorubicin of high capacity (1.15 mg mg-1) and exhibited acid-triggered and photothermally enhanced drug release behavior. The application of FCO in cancer treatment achieved much better therapeutic effects than single chemotherapy or PTT. This work established FCO as a novel nano-carrier with high PL, NIR absorbance, paramagnetism, and drug loading capacity, and demonstrated its first application in cancer chemo-photothermal therapy.

Fluorinated carbon fiber as a novel nanocarrier for cancer chemo-photothermal therapy.

Although biomedical applications of carbon materials such as fullerenes, carbon nanotubes and graphene have been intensively studied in recent years owing to their unique chemical and physical properties, fluorinated carbon fiber (FC) has been rarely explored in biomedicine, mostly because of it's large-size, needle-like structure and strong hydrophobicity. In this study, for the first time we developed a novel FC-based nano-carrier with good biocompatibility, high drug-loading capacity and enhanced photo-thermal performance. A simple and feasible strategy is first employed to transform commercial FC into nano-sized ones with good solubility in both water and culture medium. The changes in surface wettability then facilitated us to load doxorubicin (DOX) onto the FC viaπ-π stacking interactions. Successful regulation of structure and composition also endows FC with an enhanced photothermal response in the near-infrared (NIR) region. Moreover, cell experiments indicate that the constructed nanocarrier can be easily transferred into cells by endocytosis, showing low toxicity and exhibiting excellent cancer therapy effects resulting from a good combination of chemotherapy and photothermal therapy. Considering the low cost, high synthesis efficiency and outstanding properties of FC, the newly developed nanocarrier may find widespread applications in biomedicine and other related fields.

ATP-Dependent Lon Protease Contributes to Helicobacter pylori-Induced Gastric Carcinogenesis.

Helicobacter pylori infection is the strongest risk factor for development of gastric cancer. Host cellular stress responses, including inflammatory and immune responses, have been reported highly linked to H. pylori-induced carcinogenesis. However, whether mitochondrial regulation and metabolic reprogramming, which are potently associated with various cancers, play a role in H. pylori-induced gastric carcinogenesis is largely unknown. Here we revealed that Lon protease (Lonp1), which is a key inductive of mitochondrial unfolded protein response (UPR(mt)) and is required to maintain the mitochondrial quality, was greatly induced in H. pylori infected gastric epithelial cells. Importantly, we uncovered that knockdown of Lonp1 expression significantly diminished the metabolic switch to glycolysis and gastric cell proliferation associated with low multiplicity of H. pylori infection. In addition, Lonp1 overexpression in gastric epithelial cells also promoted glycolytic switch and cell overgrowth, suggesting H. pylori effect is Lonp1 dependent. We further demonstrated that H. pylori induced Lonp1 expression and cell overgrowth, at least partially, via HIF-1α regulation. Collectively, our results concluded the relevance of Lonp1 for cell proliferation and identified Lonp1 as a key regulator of metabolic reprogramming in H. pylori-induced gastric carcinogenesis.

Prophylactic Nasogastric Decompression for Routine Gastrectomy.

OBJECTIVE: To determine the necessity of using nasogastric tubes for patients with gastrectomy. STUDY DESIGN: A non-randomized controlled trial with two arms. PLACE AND DURATION OF STUDY: Sichuan Provincial Peoples' Hospital, China, from February 2012 to January 2014. METHODOLOGY: One hundred and twenty one patients undergoing gastrectomy were assigned into intubation group and control group based on patient's own will. The intubation group was intubated with a nasogastric tube before operation and extubated at the earliest evidence of passed flatus. Clinical outcomes, such as operation time, bleeding volume, time to passage of flatus, postoperative complications, and length of stay were recorded and compared between the two groups along with patient characteristics. RESULTS: The two groups did not differ in patient characteristics with similar distribution of gender, age, diagnosis, tumor location and operation type. Nasogastric intubation before surgery was not associated with statistically significant difference in total surgery duration, bleeding volume of operation or postoperative complications. In addition, patients without nasogastric tubes resumed oral diet earlier (52.5 ± 14.1 vs.18.4 ± 2.0 hours, p < 0.05) and had shorter time to first passage of flatus (43.8 ± 11.2 vs. 49.0 ± 13.3 hours, p=0.02). CONCLUSION: It is safe to give up nasogastric intubation for patients undergoing elective gastrectomy and may even result in a better patient outcome.

Epidermal growth factor receptor-coamplified and overexpressed protein (VOPP1) is a putative oncogene in gastric cancer.

MicroRNAs are found to play an important role in gastric cancer. Reduced expression of microRNA-218 (miR-218) is of key interest. The target gene of microRNA-218, epidermal growth factor receptor-coamplified and overexpressed protein (ECOP) encoded by the VOPP1 gene, has been implicated in tumorigenesis. However, few studies on expression and function of ECOP in gastric cancer have been reported. ECOP expression was determined in matched normal and gastric adenocarcinoma tissue specimens by immunohistochemistry and western blot. Subsequently, ectopic overexpression and RNAi-mediated silencing of VOPP1 was effected in the human gastric cancer cell line, AGS. Proliferation and migration of parental, VOPP1 overexpressing and VOPP1-silenced AGS cells were evaluated by cell proliferation assay and scratch wound-healing motility assay. Finally, intracellular localization of ECOP in AGS cells was assessed by green fluorescent protein tagging and fluorescent microscopy. Western blot and immunohistochemistry showed overexpression of ECOP in gastric adenocarcinoma tissues compared to matched normal tissue specimens. Ectopic overexpression and RNAi-mediated silencing of VOPP1 promoted and inhibited, respectively, cell proliferation and migration in AGS cells. Intracellular localization of ECOP in perinuclear lysosomes mimicked colocalization earlier reported for other cancerous cells. VOPP1 is overexpressed in gastric adenocarcinoma, which is involved in promoting cell proliferation and migration and thus might serve as a putative oncogene.