Prediction of tumor budding in patients with rectal adenocarcinoma using b-value threshold map.

OBJECTIVE: To investigate the feasibility of b-value threshold (bThreshold) map in preoperative evaluation of tumor budding (TB) in patients with locally advanced rectal cancer (LARC). METHODS: Patients with LARC were enrolled and underwent diffusion-weighted imaging (DWI). Contrast-to-noise ratio (CNR) between the lesions and normal tissues was assessed using DWI and bThreshold maps. TB was counted and scored using hematoxylin and eosin staining. Reproducibility for the apparent diffusion coefficient (ADC), bThreshold values, and region-of-interest (ROI) sizes were compared. Differences in ADC and bThreshold values with low-intermediate and high TB grades and the correlations between mean ADC and bThreshold values with TB categories were analyzed. Diagnostic performance of ADC and bThreshold values was assessed using area under the curve (AUC) and decision curve analysis. RESULTS: Fifty-one patients were evaluated. The CNR on bThreshold maps was significantly higher than that on DW images (9.807 ± 4.811 vs 7.779 ± 3.508, p = 0.005). Reproducibility was excellent for the ADC (ICC 0.933; CV 8.807%), bThreshold values (ICC 0.958; CV 7.399%), and ROI sizes (ICC 0.934; CV 8.425%). Significant negative correlations were observed between mean ADC values and TB grades and positive correlations were observed between mean bThreshold values and TB grades (p < 0.05). bThreshold maps showed better diagnostic performance than ADC maps (AUC, 0.914 vs 0.726; p = 0.048). CONCLUSIONS: In LARC patients, bThreshold values could distinguish different TB grades better than ADC values, and bThreshold maps may be a preoperative, non-invasive approach to evaluate TB grades. KEY POINTS: • Compared with diffusion-weighted images, bThreshold maps improved visualization and detection of rectal tumors. • Agreement and diagnostic performance of bThreshold values are superior to apparent diffusion coefficient in assessing tumor budding grades in patients with locally advanced rectal cancer. • bThreshold maps could be used to evaluate tumor budding grades non-invasively before operation.

Comparison of functional and oncological outcome of conformal sphincter preservation operation, low anterior resection, and abdominoperineal resection in very low rectal cancer: a retrospective comparative cohort study with propensity score matching.

PURPOSE: Conformal sphincter preservation operation (CSPO) procedure is a sphincter preservation procedure for preserving the anal canal function for very low rectal cancers. This study investigated the functional and oncological outcome of conformal sphincter preservation operation by comparing with low anterior resection (LAR) and abdominoperineal resection (APR). METHODS: This is a retrospective comparative study. Patients who received conformal sphincter preservation operation (n = 52), low anterior resection (n = 54), or abdominoperineal resection (n = 69) were included between 2011 and 2016 in a tertiary referral hospital. Propensity score matching was applied to adjust the baseline characteristics which may influence the choice of the surgical procedure. RESULTS: Twenty-one pairs of conformal sphincter preservation operation vs. low anterior resection and 29 pairs of conformal sphincter preservation operation vs. abdominoperineal resection were selected. The first group had a higher tumor location than the second group. Compared with the low anterior resection group, the conformal sphincter preservation operation group had shorter distal resection margins; however, no significant differences were identified in daily stool frequency, Wexner incontinence score, local recurrence, distant metastasis, overall survival, and disease-free survival between both groups. Compared with the abdominoperineal resection group, the conformal sphincter preservation operation group had shorter operative time and shorter postoperative hospital stay. No significant differences were identified in local recurrence, distant metastasis, overall survival, and disease-free survival. CONCLUSION: Conformal sphincter preservation operation is oncologically safe compared to APR and LAR, and has similar functional findings to LAR. Studies comparing CSPO with intersphincteric resection should be performed.

Adaptive Cruise System Based on Fuzzy MPC and Machine Learning State Observer.

Under the trend of vehicle intelligentization, many electrical control functions and control methods have been proposed to improve vehicle comfort and safety, among which the Adaptive Cruise Control (ACC) system is a typical example. However, the tracking performance, comfort and control robustness of the ACC system need more attention under uncertain environments and changing motion states. Therefore, this paper proposes a hierarchical control strategy, including a dynamic normal wheel load observer, a Fuzzy Model Predictive Controller and an integral-separate PID executive layer controller. Firstly, a deep learning-based dynamic normal wheel load observer is added to the perception layer of the conventional ACC system and the observer output is used as a prerequisite for brake torque allocation. Secondly, a Fuzzy Model Predictive Control (fuzzy-MPC) method is adopted in the ACC system controller design, which establishes performance indicators, including tracking performance and comfort, as objective functions, dynamically adjusts their weights and determines constraint conditions based on safety indicators to adapt to continuously changing driving scenarios. Finally, the executive controller adopts the integral-separate PID method to follow the vehicle's longitudinal motion commands, thus improving the system's response speed and execution accuracy. A rule-based ABS control method was also developed to further improve the driving safety of vehicles under different road conditions. The proposed strategy has been simulated and validated in different typical driving scenarios and the results show that the proposed method provides better tracking accuracy and stability than traditional techniques.

Measurement of distal intramural spread and the optimal distal resection by naked eyes after neoadjuvant radiation for rectal cancers.

BACKGROUND: The safe distance between the intraoperative resection line and the visible margin of the distal rectal tumor after preoperative radiotherapy is unclear. We aimed to investigate the furthest tumor intramural spread distance in fresh tissue to determine a safe distal intraoperative resection margin length. METHODS: Twenty rectal cancer specimens were collected after preoperative radiotherapy. Tumor intramural spread distances were defined as the distance between the tumor's visible and microscopic margins. Visible tumor margins in fresh specimens were identified during the operation and were labeled with 5 - 0 sutures under the naked eye at the distal 5, 6, and 7 o'clock directions of visible margins immediately after removal of the tumor. After fixation with formalin, the sutures were injected with nanocarbon particles. Longitudinal tissues were collected along three labels and stained with hematoxylin and eosin. The spread distance after formalin fixation was measured between the furthest intramural spread of tumor cells and the nanocarbon under a microscope. A positive intramural spread distance indicated that the furthest tumor cell was distal to the nanocarbon, and a negative value indicated that the tumor cell was proximal to the nanocarbon. The tumor intramural spread distance in fresh tissue during the operation was 1.75 times the tumor intramural spread distance after formalin fixation according to the literature. RESULTS: At the distal 5, 6, and 7 o'clock direction, seven (35%), five (25%), and six (30%) patients, respectively, had distal tumor cell intramural spread distance > 0 mm. The mean and 95% confidence interval of tumor cell intramural spread distance in fresh tissue during operation was - 0.3 (95%CI - 4.0 ~ 3.4) mm, - 0.9 (95%CI - 3.4 ~ 1.7) mm, and - 0.4 (95%CI - 3.5 ~ 2.8) mm, respectively. The maximal intraoperative intramural spread distances in fresh tissue were 8.8, 7, and 7 mm, respectively. CONCLUSIONS: The intraoperative distance between the distal resection line and the visible margin of the rectal tumor after radiotherapy should not be less than 1 cm to ensure oncological safety.

FoxM1 is regulated by both HIF-1α and HIF-2α and contributes to gastrointestinal stromal tumor progression.

BACKGROUND: FoxM1 plays important regulatory roles in a variety of diseases. However, the functional role of FoxM1 and mechanisms responsible for its expression in gastrointestinal stromal tumor (GIST) is not thoroughly understood. METHODS: FoxM1 protein expression and biological function were examined in human GIST tissues and cells using immunohistochemistry, quantitative real-time PCR, western blot, CCK-8, wound-healing- and Matrigel invasion assays, respectively. The role of hypoxia-inducible factor (HIF) signaling in FoxM1 expression was investigated using chromatin immunoprecipitation and luciferase reporter and in vivo tumor growth assays. RESULTS: FoxM1 was highly expressed in highly proliferative and migratory/invasive GIST specimens. Upregulation of FoxM1 was positively correlated with the expression of HIF-1α and HIF-2α in GIST specimens, and hypoxia-induced FoxM1 expression in GIST cells. Functionally, ectopic expression of FoxM1 significantly promoted GIST cell proliferation, cell cycle progression, migration and invasion, whereas the knockdown of endogenous FoxM1 of hypoxic GIST cells had the opposite effects. Molecularly, FoxM1 was transcriptionally regulated by HIF-2α under normoxia, whereas it was upregulated by both HIF-1α and HIF-2α under hypoxia. The xenograft tumor data further confirmed the regulated effect of HIF-1α and HIF-2α on FoxM1, and demonstrated that the simultaneous downregulation of both HIF-1α and HIF-2α inhibited GIST tumor growth. CONCLUSIONS: Our data demonstrated the critical role of FoxM1 in promoting GIST progression and uncovered a novel HIF-1α/HIF-2α-FoxM1 axis. These findings identify FoxM1 as a possible new molecular target for designing novel therapeutic treatments to control GIST progression.

PHD3 Stabilizes the Tight Junction Protein Occludin and Protects Intestinal Epithelial Barrier Function.

Prolyl hydroxylase domain proteins (PHDs) control cellular adaptation to hypoxia. PHDs are found involved in inflammatory bowel disease (IBD); however, the exact role of PHD3, a member of the PHD family, in IBD remains unknown. We show here that PHD3 plays a critical role in maintaining intestinal epithelial barrier function. We found that genetic ablation of Phd3 in intestinal epithelial cells led to spontaneous colitis in mice. Deletion of PHD3 decreases the level of tight junction protein occludin, leading to a failure of intestinal epithelial barrier function. Further studies indicate that PHD3 stabilizes occludin by preventing the interaction between the E3 ligase Itch and occludin, in a hydroxylase-independent manner. Examination of biopsy of human ulcerative colitis patients indicates that PHD3 is decreased with disease severity, indicating that PHD3 down-regulation is associated with progression of this disease. We show that PHD3 protects intestinal epithelial barrier function and reveal a hydroxylase-independent function of PHD3 in stabilizing occludin. These findings may help open avenues for developing a therapeutic strategy for IBD.

The Endoplasmic Reticulum Stress Sensor IRE1α in Intestinal Epithelial Cells Is Essential for Protecting against Colitis.

Intestinal epithelial cells (IECs) have critical roles in maintaining homeostasis of intestinal epithelium. Endoplasmic reticulum (ER) stress is implicated in intestinal epithelium homeostasis and inflammatory bowel disease; however, it remains elusive whether IRE1α, a major sensor of ER stress, is directly involved in these processes. We demonstrate here that genetic ablation of Ire1α in IECs leads to spontaneous colitis in mice. Deletion of IRE1α in IECs results in loss of goblet cells and failure of intestinal epithelial barrier function. IRE1α deficiency induces cell apoptosis through induction of CHOP, the pro-apoptotic protein, and sensitizes cells to lipopolysaccharide, an endotoxin from bacteria. IRE1α deficiency confers upon mice higher susceptibility to chemical-induced colitis. These results suggest that IRE1α functions to maintain the intestinal epithelial homeostasis and plays an important role in defending against inflammation bowel diseases.

The golden key to open mystery boxes of SMARCA4-deficient undifferentiated thoracic tumor: focusing immunotherapy, tumor microenvironment and epigenetic regulation.

SMARCA4-deficient undifferentiated thoracic tumor is extremely invasive. This tumor with poor prognosis is easily confused with SMARCA4-deficent non-small cell lung cancer or sarcoma. Standard and efficient treatment has not been established. In this review, we summarized the etiology, pathogenesis and diagnosis, reviewed current and proposed innovative strategies for treatment and improving prognosis. Immunotherapy, targeting tumor microenvironment and epigenetic regulator have improved the prognosis of cancer patients. We summarized clinicopathological features and immunotherapy strategies and analyzed the progression-free survival (PFS) and overall survival (OS) of patients with SMARCA4-UT who received immune checkpoint inhibitors (ICIs). In addition, we proposed the feasibility of epigenetic regulation in the treatment of SMARCA4-UT. To our knowledge, this is the first review that aims to explore innovative strategies for targeting tumor microenvironment and epigenetic regulation and identify potential benefit population for immunotherapy to improve the prognosis.

Use of Hydrogen-Rich Gas in Blast Furnace Ironmaking of V-bearing Titanomagnetite: Mass and Energy Balance Calculations.

The iron and steel industry is a major CO2 emitter and an important subject for the implementation of carbon emission reduction goals and tasks. Due to the complex ore composition and low iron grade, vanadium-bearing titanomagnetite smelting in a blast furnace consumes more coke and emits more carbon than in an ordinary blast furnace. Injecting hydrogen-rich gas into blast furnace can not only partially replace coke, but also reduce the carbon emission. Based on the whole furnace and zonal energy and mass balance of blast furnace, the operation window of the blast furnace smelting vanadium-bearing titanomagnetite is established in this study on the premise that the thermal state of the blast furnace is basically unchanged (raceway adiabatic flame temperature and top gas temperature). The effects of different injection amounts of hydrogen-rich gases (shale gas, coke oven gas, and hydrogen) on raceway adiabatic flame temperature and top gas temperature, and the influence of blast temperature and preheating temperature of hydrogen-rich gases on operation window are calculated and analyzed. This study provides a certain theoretical reference for the follow-up practice of hydrogen-rich smelting of vanadium-bearing titanomagnetite in blast furnace.

Neoadjuvant sintilimab and chemotherapy in patients with resectable esophageal squamous cell carcinoma: A prospective, single-arm, phase 2 trial.

Background: Immunotherapy (Programmed cell death 1 blockade) has entered the ranks of advanced esophageal cancer first-line treatment; however, little is known about the efficacy of PD-1 inhibitor as neoadjuvant therapy in resectable esophageal squamous cell carcinoma (ESCC). We aim to evaluate the activity and safety of the neoadjuvant sintilimab combined with chemotherapy in the treatment of resectable thoracic ESCC. Methods: The enrolled patients with resectable (clinical stage II to IVA) ESCC received neoadjuvant sintilimab injection (200 mg/time, day 1), paclitaxel liposomes (135 mg/m2, day 1), and carboplatin (area under curve of 5 mg/mL/min, day 1) every 21 days for 2 cycles, and esophagectomy was performed within 3-6 weeks after the 2 cycles of treatment. The primary endpoint of the study was the pathological complete response (PCR) rate. Results: From July 2019 to March 2021, a total of 47 patients were enrolled, of which 33 patients (70.2%) had clinical stage III disease. All patients completed the full two-cycle treatment and forty-five patients received radical surgery, including 44 (97.8%) R0 resections. Ten (22.2%) of 45 patients had a PCR, and the major pathological response (MPR) rate was 44.4% (20/45). The grade 3-4 treatment-related adverse events (TRAEs) were mainly neutropenia (6 of 47,12.8%) and leucopenia (8 of 47,17.0%). One (2.1%) patient occurred postoperative immune-associated encephalitis. No delays in surgery were observed. Conclusions: sintilimab combined with paclitaxel liposome and carboplatin, as demonstrated in this phase II trial to exhibit a relatively high PCR rate and acceptable safety, warrants additional investigation in resectable ESCC. Trial Registration: http://www.chictr.org.cn/, ChiCTR1900026593.

A new monoclonal antibody that blocks dimerisation and inhibits c-kit mutation-driven tumour growth.

PURPOSE: Imatinib, a small-molecule tyrosine kinase inhibitor, has shown good clinical activity by inhibiting adenosine triphosphate (ATP) binding to the receptor. Unfortunately, majority of patients eventually develop drug resistance, which limits the long-term benefits of the tyrosine kinase inhibitors and poses a significant challenge in the clinical management of GIST. The aim of our study was to explore the feasibility of blocking KIT dimerisation upstream of the phosphorylation in imatinib-resistant GIST. METHOD: KITMAb was prepared using hybridoma technique. The biological function of KITMAb was examined in KIT-dimer-expressing cells constructed by transfecting with liposomes using enzyme linked immunosorbent assay (ELISA), immunohistochemistry, western blot, MTT, Annexin V/FITC, and flow cytometry assay, respectively. RESULTS: KIT-dimer was expressed in 293 cells transfected with c-kit mutated-type pcDNA3.1. Treatment of KIT-dimer-expressing cells with the KITMAb significantly decreased the expression of both KIT-dimer and other phosphorylated proteins of KIT downstream signalling pathway. Furthermore, KITMAb slowed down cell growth and reduced the proportion of cells in the proliferative phase (S + G2-M). Finally, we also found that KITMAb treatment accelerated cell apoptosis. These results indicate that KITMAb strongly inhibits KIT receptor dimerisation-mediated signalling pathway and cell growth responses in vitro. CONCLUSIONS: We demonstrate c-kit mutation-driven KIT auto-dimerisation prior to tyrosine kinase phosphorylation as same as the procedure in ligand-dependent signalling pathway and describe a monoclonal antibody, KITMAb, with strong affinity to the dimerisation domain of KIT that blocks the important step in both the KIT signalling pathways. Further, the results suggest that treatment with KITMAb may be potentially therapeutic in imatinib-resistant GIST.

Rectal clear cell sarcoma-a case report.

Gastrointestinal clear cell sarcomas (GICCSs) are malignant mesenchymal tumour that occur in the wall of gastrointestinal tract, mostly in the ileum and rarely in the rectum. These tumours are highly invasive, and often have metastasized via the lymphatic system or bloodstream by the time of diagnosis. In this case, the patient was admitted for gastric fundus mass, who was subsequently found and confirmed by biopsy as clear cell sarcoma of rectum. Computed tomography (CT) and magnetic resonance imaging (MRI) showed multiple metastatic lesions in lymph node, lung, liver and bone. Furthermore, energy spectrum CT was used to confirm that the nature of gastric fundus mass and rectal lesion were consistent. So, this case may be multiple clear cell sarcomas in the rectum and stomach or clear cell sarcoma in the rectum with gastric fundus metastasis. Unfortunately, after several days of immunotherapy, the patient died due to abnormal liver function. At present, GICCS mainly relies on surgical resection, and the effect of radiotherapy and chemotherapy is not good. Therefore, how to find lesions as earlier as possible and make accurate diagnosis is particularly important. CT and MRI are essential examinations in the diagnosis of tumors. Whether they are helpful for the diagnosis of GICCS is the focus of our attention.

Corrigendum to "The Prognostic Significance of Tumor Deposit Count for Colorectal Cancer Patients after Radical Surgery".

[This corrects the article DOI: 10.1155/2020/2052561.].

The Prognostic Significance of Tumor Deposit Count for Colorectal Cancer Patients after Radical Surgery.

BACKGROUND: The prognostic value of tumor deposit (TD) count in colorectal cancer (CRC) patients has been rarely evaluated. This study is aimed at exploring the prognostic value of TD count and finding out the optimal cutoff point of TD count to differentiate the prognoses of TD-positive CRC patients. METHOD: Patients diagnosed with CRC from Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2012, were analyzed. X-tile program was used to identify the optimal cutoff point of TD count in training cohort, and a validation cohort was used to test this cutoff point after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard models were used to assess the risk factors of survival. RESULTS: X-tile plots identified 3 (P < 0.001) as the optimal cutoff point of TD count to divide the patients of training cohort into high and low risk subsets in terms of disease-specific survival (DSS). This cutoff point was validated in validation cohort before and after PSM (P < 0.001, P = 0.002). More TD count, which was defined as more than 3, was validated as an independent risk prognostic factor in univariate and multivariate analysis (P < 0.001). CONCLUSION: More TD count (TD count ≥ 4) was significantly associated with poor disease-specific survival in CRC patients.

Integrated Omics of Metastatic Colorectal Cancer.

We integrate the genomics, proteomics, and phosphoproteomics of 480 clinical tissues from 146 patients in a Chinese colorectal cancer (CRC) cohort, among which 70 had metastatic CRC (mCRC). Proteomic profiling differentiates three CRC subtypes characterized by distinct clinical prognosis and molecular signatures. Proteomic and phosphoproteomic profiling of primary tumors alone successfully distinguishes cases with metastasis. Metastatic tissues exhibit high similarities with primary tumors at the genetic but not the proteomic level, and kinase network analysis reveals significant heterogeneity between primary colorectal tumors and their liver metastases. In vivo xenograft-based drug tests using 31 primary and metastatic tumors show personalized responses, which could also be predicted by kinase-substrate network analysis no matter whether tumors carry mutations in the drug-targeted genes. Our study provides a valuable resource for better understanding of mCRC and has potential for clinical application.

Self-renewal and chemotherapy resistance of p75NTR positive cells in esophageal squamous cell carcinomas.

BACKGROUND: p75NTR has been used to isolate esophageal and corneal epithelial stem cells. In the present study, we investigated the expression of p75NTR in esophageal squamous cell carcinoma (ESCC) and explored the biological properties of p75NTR+ cells. METHODS: p75NTR expression in ESCC was assessed by immunohistochemistry. p75NTR+ and p75NTR- cells of 4 ESCC cell lines were separated by fluorescence-activated cell sorting. Differentially expressed genes between p75NTR+ and p75NTR- cells were determined by real-time quantitative reverse transcription-PCR. Sphere formation assay, DDP sensitivity assay, 64copper accumulation assay and tumorigenicity analysis were performed to determine the capacity of self-renewal, chemotherapy resistance and tumorigenicity of p75NTR+ cells. RESULTS: In ESCC specimens, p75NTR was found mainly confined to immature cells and absent in cells undergoing terminal differentiation. The percentage of p75NTR+ cells was 1.6%-3.7% in Eca109 and 3 newly established ESCC cell lines. The expression of Bmi-1, which is associated with self-renewal of stem cells, was significantly higher in p75NTR+ cells. p63, a marker identified in keratinocyte stem cells, was confined mainly to p75NTR+ cells. The expression of CTR1, which is associated with cisplatin (DDP)-resistance, was significantly decreased in p75NTR+ cells. Expression levels of differentiation markers, such as involucrin, cytokeratin 13, beta1-integrin and beta4-integrin, were lower in p75NTR+ cells. In addition, p75NTR+ cells generated both p75NTR+ and p75NTR- cells, and formed nonadherent spherical clusters in serum-free medium supplemented with growth factors. Furthermore, p75NTR+ cells were found to be more resistant to DDP and exhibited lower 64copper accumulation than p75NTR- cells. CONCLUSION: Our results demonstrated that p75NTR+ cells possess some characteristics of CSCs, namely, self-renewal and chemotherapy resistance. Chemotherapy resistance of p75NTR+ cells may probably be attributable to decreased expression of CTR1.

[Transforming effect of PDGFRA gene mutant on the cell function in gastrointestinal stromal tumor].

OBJECTIVE: To explore the effect of malignant transformation of the L839P, a new mutation site of the PDGFRA gene, on the pathogenesis of gastrointestinal stromal tumors. METHODS: All recombinant plasmids were stably transfected into CHO cells by liposomes. Western blotting was used to detect the expression of PDGFRA protein. The cell growth curve was plotted by cell counting. Flow cytometry was used to detect the cell cycle and apoptosis of CHO cell, respectively. The stably transformed cells were inoculated subcutaneously into the back of nude mice and the mice were used to observe the tumorigenesis. Transient transfection of the mutant-type plasmids of PDGFRA gene and the wild-type plasmids of kit gene into the CHO cells was performed. Western blot was used to detect the expression of kit protein and its phosphorylated forms. RESULTS: PDGFRA protein expressed in the negative control, experimental group and positive control, except the empty vector. The growth curve showed that it was accelerated in the experimental group and positive control. The ratios of cells in proliferative phase were 28.4% (blank), 24.5% (negative control), 43.8% (experimental group) and 40.9% (positive control). Their apoptotic indexes were 1.8%, 1.9%, 1.5% and 1.6%, respectively. After three weeks, tumors were observed in the nude mice of experimental group and positive control, inoculated with the stably transformed cells. Moreover, the expression of phosphorylated protein of kit was enhanced after cotransfection of the mutant-type plasmids of PDGFRA and the wild-type plasmid of kit. CONCLUSION: The PDGFRA mutant L839P is a gain-of-function mutation and has obviously malignant transforming effect on normal cells, and may activate kit protein accelerating the tumorigenesis. Gastrointestinal stromal tumors;

Antitumor effect of curcumin liposome after transcatheter arterial embolization in VX2 rabbits.

BACKGROUND: Hypoxia may affect the therapeutic efficacy of transcatheter arterial embolization (TAE), which is widely used in nonsurgical hepatocellular carcinoma (HCC). Liposomal curcumin can exert anticancer effect. Our purpose is to explore the antitumor effect of liposomal curcumin on the HCC after TAE. METHODS: The HepG2 cells were cultured under hypoxic condition (1% O2) and then treated with curcumin liposome. Cell viability, apoptosis and cell cycle were respectively measured by CCK-8 and a flow cytometry. The VX2 rabbits were randomly distributed into three groups: control group with saline embolization, TAE group with lipiodol embolization and curcumin liposome group with curcumin liposome and lipiodol embolization. MRI and CT perfusion scanning were performed after embolization. The hepatocyte apoptosis was measured by the terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL). The vascular endothelial growth factor (VEGF) and microvessel density (MVD) were measured by immunohistochemical. RT-PCR and Western blot were performed to examine mRNA and protein levels. RESULTS: By regulating the apoptosis-related molecules, curcumin liposome obviously inhibited the cell viability and promoted the apoptosis in G1 phase. Curcumin liposome reduced the tumor size and alleviated neoplasia in VX2 rabbits. Curcumin liposome decreased the expressions of MVD and VEGF and increased the apoptosis of liver tissues. The levels of hypoxia-inducible factor-1α (HIF-1α) and survivin were suppressed by curcumin liposome both in hypoxic cells and liver tissues in the VX2 rabbits. CONCLUSION: Curcumin liposome exerted antitumor effect by regulating the proliferation- and apoptosis-related molecules. Curcumin liposome suppressed the HIF-1α and survivin levels and inhibited the angiogenesis in VX2 rabbits after TAE.

Diagnostic performance in T staging for patients with esophagogastric junction cancer using high-resolution MRI: a comparison with conventional MRI at 3 tesla.

BACKGROUND: To investigate and compare the diagnostic performance in T staging for patients with esophagogastric junction cancer using high-resolution magnetic resonance imaging (HR MRI), as compared with conventional MRI at 3 Tesla. METHODS: A total of 118 patients with pathologically confirmed esophagogastric junction cancer were included and underwent multiparameter HR MRI (Cohort 1, 62 patients) or conventional MRI (Cohort 2, 56 patients). T2-weighted, T1-weighted, diffusion-weighted and contrast-enhanced T1-weighted images of each patient were evaluated by two radiologists who determined the preoperative T staging by consensus. Using pathologic staging as the gold standard, the consistency between HR MRI and pathology and between conventional MRI and pathology in T staging was calculated and compared. The overall accuracy, overstatement and understatement of HR MRI and conventional MRI in T staging of patients with esophagogastric junction cancer were computed and compared. Moreover, the diagnostic performance of HR MRI and conventional MRI in T staging (≤ T1 and ≥ T4) of patients with esophagogastric junction cancer were evaluated. RESULTS: There were no significant differences in age (p = 0.465) and sex (p = 0.175) between Cohorts 1 and 2. Excellent agreement was observed in the T staging of patients with esophagogastric junction cancer between pathology and HR MRI (kappa = 0.813), while moderate agreement was observed between pathology and conventional MRI (kappa = 0.486). Significant differences were observed in overall accuracy (88.7% vs 64.3%, p = 0.002) and understatement (1.6% vs 26.8%, p < 0.001) but not for overstatement (9.7% vs 8.9%, p = 0.889) in T staging between HR MRI and conventional MRI techniques. For differentiating the T stages of ≤ T1 from ≥ T2 and the T stages of ≤ T3 from ≥ T4, no significant differences were observed between the imaging techniques. CONCLUSIONS: HR MRI has good diagnostic performance and may serve as an alternative technique in the T staging of patients with esophagogastric junction cancer in clinical practice.

Therapeutic potential of angiogenin modified mesenchymal stem cells: angiogenin improves mesenchymal stem cells survival under hypoxia and enhances vasculogenesis in myocardial infarction.

BACKGROUND: To examine the effects of angiogenin modified mesenchymal stem cells (MSCs) on ventricular remodeling and cardiac function in a rat model of acute myocardial infarction. METHODS: MSCs were transfected with adenoviral vectors carrying either angiogenin (MSC(AdANG)) or EGFP (MSC(AdEGFP)). Angiogenin gene amplification, protein expression and cell death were assayed after hypoxic treatment. DiI labeled MSC(AdANG) and MSC(AdEGFP) were injected into infracted heart. Six weeks after cell transplantation, echocardiography and histological study were performed. RESULTS: After hypoxia treatment, angiogenin modified MSCs effectively expressed angiogenin for at least 14 days. The death of MSC(AdANG) was one-third of MSCAd(EGFP), and 50% of untreated MSCs. In the infracted myocardium, the number of DiI labeling cells in MSC(AdANG) group with high angiogenin expression was three-fold that in MSC(AdEGFP) group. Echocardiograms suggested that angiogenin modified MSCs significantly improved left ventricular (LV) systolic and diastolic function. Histological study confirmed that ventricular remodeling was attenuated significantly in MSC(AdANG) group. Furthermore, vasculogenesis was enhanced significantly in MSC(AdANG) group as measured by both factor VIII and alpha-SMA staining. CONCLUSION: Angiogenin modified MSCs enhanced the tolerance of engrafted MSCs to hypoxia injury in vitro and improved their viability in infracted hearts, thus helping preserve the LV contractile function and attenuate LV remodeling through vasculogenesis.