GSH-activated Porphyrin Sonosensitizer Prodrug for Fluorescence Imaging-guided Cancer Sonodynamic Therapy.

Sonodynamic therapy (SDT), which uses ultrasound to trigger a sonosensitizer to generate reactive oxygen species (ROS), is a promising form of cancer therapy with outstanding tissue penetration depth. However, the sonosensitizer may inevitably spread to surrounding healthy tissue beyond the tumor, resulting in undesired side effects under an ultrasound stimulus. Herein, as glutathione (GSH) is overexpressed in the tumor microenvironment, a GSH-activatable sonosensitizer prodrug was designed by attaching a quencher to tetraphydroxy porphyrin for tumor therapy. The prodrug exhibited poor fluorescence and low ROS generation capacity under ultrasound irradiation but it can be activated by GSH to simultaneously switch on fluorescence emission and ROS generation in tumor site. Compared with the non-quenched sonosensitizer, the designed prodrug exhibited significantly higher tumor/healthy organ fluorescence ratios, due to the specific fluorescence and ROS activation by overexpressed GSH in the tumor. Finally, the prodrug exhibited efficient tumor growth inhibition under ultrasound irradiation, further demonstrating its promise as a GSH-activated sonosensitizer prodrug for highly effective cancer treatment.

Ultrasmall iron-quercetin metal natural product nanocomplex with antioxidant and macrophage regulation in rheumatoid arthritis.

Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.

The combination of eddy thermal effect of biodegradable magnesium with immune checkpoint blockade shows enhanced efficacy against osteosarcoma.

Osteosarcoma (OS) patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis. Magnetic hyperthermia therapy (MHT) combined with immunotherapy is an effective strategy to treat solid and metastatic tumors. Here, we combined biodegradable magnesium (Mg) macroscale rods, which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field, and immunotherapy to achieve a radical cure for OS. The eddy thermal effect (ETE) of the Mg rods (MgR) showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells (DCs), and the mild MHT induced the immunogenic cell death (ICD) in the OS cells. Combined with immune checkpoint blockade (ICB) therapy, we obtained an excellent curative effect against OS, and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages. Interestingly, the biodegradable MgR also promoted bone osteogenesis. Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment (TME), which would inspire the application of MHT for the effective treatment of OS.

Oxygen-Deficient Molybdenum Oxide Nanosensitizers for Ultrasound-Enhanced Cancer Metalloimmunotherapy.

Oxygen-deficient molybdenum oxide (MoOX ) nanomaterials are prepared as novel nanosensitizers and TME-stimulants for ultrasound (US)-enhanced cancer metalloimmunotherapy. After PEGylation, MoOX -PEG exhibits efficient capability for US-triggered reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Under US irradiation, MoOX -PEG generates a massive amount of ROS to induce cancer cell damage and immunogenic cell death (ICD), which can effectively suppress tumor growth. More importantly, MoOX -PEG itself further stimulates the maturation of dendritic cells (DCs) and triggeres the activation of the cGAS-STING pathway to enhance the immunological effect. Due to the robust ICD induced by SDT and efficient DC maturation stimulated by MoOX -PEG, the combination treatment of MoOX -triggered SDT and aCTLA-4 further amplifies antitumor therapy, inhibits cancer metastases, and elicits robust immune responses to effectively defeat abscopal tumors.

Oxygen-Deficient Tungsten Oxide (WOx) Nanobelts with pH-Sensitive Degradation for Enhanced Sonodynamic Therapy of Cancer.

The further bioapplications of sonodynamic therapy (SDT) were hindered by the inadequate efficiency and poor degradability of sonosensitizers and the hypoxic tumor microenvironment (TME). Therefore, it is ideal to develop pH-sensitive sonosensitizers that generate abundant reactive oxygen species (ROS) and rapidly degrade in a neutral environment while slowly degrading in an acidic environment to reduce their long-term toxicity. Herein, the defective tungsten oxide nanobelts (WOx NBs) were developed as a type of pH-sensitive and biodegradable sonosensitizers with a high SDT efficiency and low toxicity for enhanced SDT. The defective oxygen sites of WOx NBs could inhibit the recombination of electrons and holes, making WOx NBs promising sonosensitizers that could generate abundant ROS under ultrasound (US) irradiation. Enhanced by the catalase (CAT) that reacted with H2O2 to generate O2, the WOx NBs exhibited better SDT performance against 4T1 cells in both normoxic and hypoxic environments. In addition, the WOx NBs could degrade by releasing protons (H+), resulting in intracellular acidification and inhibited cell motility that further enhanced the therapeutic effects of SDT. Assisted with CAT and ALG for hypoxia refinement and better retention, the WOx NBs enabled effective SDT and antimetastasis against 4T1 tumors in vivo. Most importantly, the WOx NBs could degrade rapidly in normal tissues but slowly in an acidic TME, which was favorable for their fast clearance, without any obvious long-term toxicity. Our work developed defective WOx NBs with a high SDT efficiency and pH-sensitive degradation for enhanced SDT, which extended the biomedical application of tungsten-based nanomaterials and the further development of SDT.

HX V2 O5 Nanocatalysts Combined with Ultrasound for Triple Amplification of Oxidative Stress to Enhance Cancer Catalytic Therapy.

Multiple amplification of tumor oxidative stress has been demonstrated as efficient strategy to enhance the reactive oxygen species (ROS)-mediated cancer therapy. Herein, vanadium-based nanocatalysts, hydrogen vanadium bronzes (HX V2 O5 , for short HVO), were constructed and employed as novel biocatalysts for amplifying tumor oxidative stress and enhancing cancer catalytic therapy. Such HVO nanocatalysts harboring multivalent V element possessed multi-functional catalytic activity in decomposing H2 O2 into ⋅OH and depleting endogenous glutathione (GSH) to dually amplify tumor oxidative stress. Meanwhile, HVO nanocatalysts could also be activated by ultrasound to further triply amplify oxidative stress. The massive intracellular ROS caused mitochondrial dysfunction, DNA damage, cell cycle arrest, and cell proliferation inhibition, further realizing cancer cell death and tumor growth inhibition. Collectively, HVO nanocatalysts highlight the remarkable value of ROS-mediated cancer therapies.

yggS Encoding Pyridoxal 5'-Phosphate Binding Protein Is Required for Acidovorax citrulli Virulence.

Bacterial fruit blotch, caused by seed-borne pathogen Acidovorax citrulli, poses a serious threat to the production of cucurbits globally. Although the disease can cause substantial economic losses, limited information is available about the molecular mechanisms of virulence. This study identified that, a random transposon insertion mutant impaired in the ability to elicit a hypersensitive response on tobacco. The disrupted gene in this mutant was determined to be Aave_0638, which is predicted to encode a YggS family pyridoxal phosphate-dependent enzyme. YggS is a highly conserved protein among multiple organisms, and is responsible for maintaining the homeostasis of pyridoxal 5'-phosphate and amino acids in cells. yggS deletion mutant of A. citrulli strain XjL12 displayed attenuated virulence, delayed hypersensitive response, less tolerance to H2O2 and pyridoxine, increased sensitivity to antibiotic ß-chloro-D-alanine, and reduced swimming. In addition, RNA-Seq analysis demonstrated that yggS was involved in regulating the expression of certain pathogenicity-associated genes related to secretion, motility, quorum sensing and oxidative stress response. Importantly, YggS significantly affected type III secretion system and its effectors in vitro. Collectively, our results suggest that YggS is indispensable for A.citrulli virulence and expands the role of YggS in the biological processes.

Galectin-1 promotes vasculogenic mimicry in gastric adenocarcinoma via the Hedgehog/GLI signaling pathway.

BACKGROUND: Galectin-1 (GAL-1), which is encoded by LGALS1, promotes vasculogenic mimicry (VM) in gastric cancer (GC) tissue. However, the underlying mechanism remains unclear. METHODS: Immunohistochemical (IHC) and CD34-periodic acid-Schiff (PAS) double staining were used to investigate Glioma-associated oncogene-1(GLI1) expression and VM in paraffin-embedded sections from 127 patients with GC of all tumor stages. LGALS1 or GLI1 were stably transduced into MGC-803 cells and AGS cells, and western blotting, IHC, CD34-PAS double staining and three-dimensional culture in vitro, and tumorigenicity in vivo were used to explore the mechanisms of GAL-1/ GLI1 promotion of VM formation in GC tissues. RESULTS: A significant association between GAL-1 and GLI1 expression was identified by IHC staining, as well as a significant association between GLI1 expression and VM formation. Furthermore, overexpression of LGALS1 enhanced expression of GLI1 in MGC-803 and AGS cells. GLI1 promoted VM formation both in vitro and in vivo. The effects of GLI1 on VM formation were independent of LGALS1. Importantly, the expression of VM-related molecules, such as MMP2, MMP14 and laminin5γ2, was also affected upon GLI1 overexpression or silencing in GC cell lines. CONCLUSION: GAL-1 promotes VM in GC through the Hh/GLI pathway, which has potential as a novel therapeutic target for treatment of VM in GC.

High versus low ligation of inferior mesenteric artery during laparoscopic radical resection of rectal cancer: A retrospective cohort study.

Laparoscopic radical resection is standard treatment for resectable rectal cancer. However, whether high or low inferior mesenteric artery (IMA) ligation should be performed remains controversial. This retrospective cohort study compared the advantages and disadvantages of low vs high IMA ligation in patients undergoing laparoscopic total mesorectal excision for rectal cancer.Rectal cancer patients (n = 322) undergoing total mesorectal excision at our institution in 2010 to 17 were enrolled; 174 underwent high IMA ligation group and 148 low IMA ligation (LIMAL group). Baseline data on patients, operative indices, economic indices, pathology findings, perioperative complications, and survival in the 2 groups were analyzed retrospectively.The low IMA ligation group had significantly higher anus retention ratio (P = .022), shorter hospital stay (P = .025), lower medical expenses (P = .032), fewer cases of anastomotic leakage (P = .023) and anastomotic stricture (P < .001), and lower incidence of postoperative genitourinary dysfunction (P = .003). Cox regression analysis indicated that local recurrence, distant metastasis, tumor differentiation, and tumor-node-metastasis stage were independently associated with survival.Low ligation of the IMA during laparoscopic radical resection of rectal cancer appears to be associated with a lower risks for anastomotic leakage, anastomotic stricture, and genitourinary dysfunction, a shorter hospital stay, and lower costs. In contrast, the rate of lymph node harvest, tumor recurrence rate, metastasis, or mortality was not found to be related with the level of IMA ligation.

Galectin-1 Promotes Vasculogenic Mimicry in Gastric Cancer by Upregulating EMT Signaling.

Background: Galectin-1 (Gal-1) expression was positively associated with vasculogenic mimicry (VM) in primary gastric cancer (GC) tissue, and that both Gal-1 expression and VM in GC tissue are indicators of poor prognosis. However, whether Gal-1 promotes VM, and by what mechanismsremains unknown. Methods: To investigate the underlying mechanisms,wound healing assay, proliferation assay, invasion assay, and three-dimensional culture were used to evaluate the invasion, metastasis and promoted VM formation effects of the Gal-1. We monitored the expression level of sociated proteins in GC tissues, cell lines in vitro and nude mice tumorigenicity in vivo by immunohistochemistry and western blot. Results: Gal-1 overexpression significantly promoted the proliferation, invasion, migration, and VM formation of MGC-803 cells. Gal-1 was associated with E-cadherin and vimentin in vitro and in clinical samples. The epithelial-to-mesenchymal transition (EMT) induced in MGC-803 cells by TGF-ß1 was accompanied by Gal-1 activation and promotion of VM formation, while knockdown of Gal-1 reduced the response to TGF-ß1, suggesting that Gal-1 promotes VM formation by activating EMT signaling. Overexpression of Gal-1 accelerated subcutaneous xenograft growth and facilitated pulmonary metastasis in athymic mice, enhanced the expression of EMT markers, and promoted VM formation in vivo. Conclusion: Our results indicated that Gal-1 promotes VM in GC by upregulating EMT signaling; thus, Gal-1 and this pathway are potential novel targets to treat VM in GC.

Isotactic-Polypropylene/Atactic-Polystyrene Miktoarm Star Copolymers: Synthesis and Aggregation Morphology.

In this work, a series of isotactic-polypropylene/atactic-polystyrene (iPP/aPS) miktoarm star copolymers, PxSy, was synthesized via an arm-first approach. Varied star macromolecule architectures were fabricated by designing the arm length and the arm numbers (x and y). These miktoarm stars were able to form micelles in selective solvent (N,N'-dimethylformamide (DMF)), in which the insoluble iPP arms formed the core and the soluble aPS arms formed the shell. The miktoarm polymers aggregated to micro-nanoscale binary structures (MNBSes) in the casting process, and their morphologies, including the MNBS shape and size, were greatly influenced by the PxSy architectures. The MNBSes endowed the material surface with superhydrophobic performance with a water contact angle of 157.0° and a sliding angle of 1.5°.

Single vs. double purse-string anastomosis during laparoscopic low anterior rectal resection (SINGLE-DOUBLE trial): study protocol for a randomized controlled trial.

BACKGROUND: An inappropriate anastomosis method during laparoscopic anterior rectal resection can increase the risk of anastomotic complications and affect surgical, economic, and oncological outcomes. The aim of this study is to compare the incidence of anastomotic complications and the surgical, economic, and oncological outcomes following single versus double purse-string anastomosis during laparoscopic total mesorectal excision (TME) for low rectal cancer. METHODS/DESIGN: This randomized controlled trial (the SINGLE-DOUBLE study) will randomly assign middle and low rectal adenocarcinoma patients to receive either single or double purse-string anastomosis during laparoscopic low anterior rectal resection. Patients will be eligible for inclusion only if they (1) have adenocarcinoma confirmed by preoperative colonoscopy and biopsy, (2) have a tumor situated less than 12 cm from the anal verge, (3) do not have the anal sphincter involved, and (4) do not have distant metastases. The primary endpoint measure will be the incidence of anastomotic complications (leakage, narrowing, and bleeding). The secondary endpoints will be surgical, economic, and oncological outcomes. A total of 500 patients will be enrolled in the study. Sample size calculation was based on previous reports and our retrospective analysis. DISCUSSION: This randomized single-center controlled trial is expected to demonstrate which anastomosis method (single or double purse-string anastomosis) is better for reducing complications and improving prognosis in rectal cancer patients undergoing laparoscopic TME for low or middle rectal cancer. TRIAL REGISTRATION: Registration number: ChiCTR 1800016116 . Protocol Registration Receipt: May 13, 2018.

Aberrant Cytokeratin 20 mRNA Expression in Peripheral Blood and Lymph Nodes Indicates Micrometastasis and Poor Prognosis in Patients With Gastric Carcinoma.

Several studies suggest that peripheral blood and lymph node micrometastases may be a causative factor for gastric cancer recurrence. Cytokeratin 20 shows enriched expression in intestinal epithelial cells. This study aimed to evaluate the clinical utility of monitoring cytokeratin 20 levels in peripheral blood and lymph nodes of patients with gastric cancer for detecting micrometastasis and predicting prognosis. We detected messenger RNA levels of cytokeratin 20 in gastric cancer cell lines and in the peripheral blood of 125 patients (85 patients with gastric cancer and 40 patients with benign neoplasm) by fluorescence quantitative real-time polymerase chain reaction both before and after radical resection. In all, 1586 lymph node samples from 85 patients with gastric cancer were evaluated for cytokeratin 20 expression using real-time polymerase chain reaction, as well as by immunohistochemistry staining with anti-pan-keratin and anti-cytokeratin 20 antibodies. All patients underwent follow-up until cancer-related death or for more than 3 years after tumor resection. We found that elevated cytokeratin 20 expression in peripheral blood as detected by quantitative real-time polymerase chain reaction closely correlates with poor clinicopathological characteristics. Detecting cytokeratin 20 messenger RNA in the lymph nodes by quantitative real-time polymerase chain reaction enabled more accurate determination of the clinicopathological staging of gastric cancer, best treatment approach, and prognosis. Our findings show that patients with increased cytokeratin 20 messenger RNA expression in the peripheral blood or lymph nodes have a shorter time to recurrence and poorer overall survival.

[Application of double-pouch anastomosis in laparoscopic radical resection of rectal cancer assisted by small incision].

OBJECTIVE: To explore the feasibility, safety and the economical efficiency of double-pouch anastomosis in laparoscopic radical rectal cancer assisted by small incisions. METHODS: Clinical data of 224 patients undergoing gastrointestinal surgery at Taizhou People's Hospital of Jiangsu Province from January 2011 to December 2017 were retrospectively analyzed. Indusion criteria: patients were diagnosed as primary rectal adenocarcinoma by preoperative enteroscopy pathology, the distance of the tumor to anal margin was from 4 to 15 cm, and patients were treated with laparoscopic total mesorectal excision(TME) through small incision. Patients were divided into two groups according to different anastomosis method, double-pouch group(108 cases) and single-pouch group (116 cases). The surgical indexes, tumor safety indexes, short-term efficacy and economic indexes were compared between the two groups. RESULTS: There was no significant difference between two groups in baseline data, operative time, blood loss, number of lymph nodes dissection, average length of proximal and distal bowel, or incidence of urination and sexual dysfunction (all P>0.05). Compared with the single-pouch group, the double-pouch group presented lower anastomotic secondary bleeding rate [0.9%(1/108) vs. 6.0% (7/116), χ²=4.238, P=0.040], lower incidence of anastomotic leakage[1.9%(2/108) vs. 7.8%(9/116), χ²=4.179, P=0.041], lower incidence of anastomotic stricture [1.9% (2/108) vs. 8.6% (10/116), χ²=5.054, P=0.025], shorter hospital stay [(13.4±3.9) days vs. (15.9±9.8) days, t=2.524, P=0.013] and less average hospitalization costs [(34 000±7 000) yuan vs. (46 000±23 000) yuan, t=5.047,P<0.001]. There was no significant difference in local recurrence, distant metastasis or overall survival between the two groups during mean follow-up of 33 months (all P>0.05). CONCLUSION: Laparoscopic TME assisted by small incision with double-pouch anastomosis is a safe, feasible and economical method.

Galectin-1 Promotes Metastasis in Gastric Cancer Through a Sphingosine-1-Phosphate Receptor 1-Dependent Mechanism.

BACKGROUND/AIMS: Increased expression of galectin-1 (Gal-1) in gastric cancer (GC) promotes metastasis and correlates with poor prognosis. The mechanisms by which Gal-1 promotes GC metastasis remain unknown. METHODS: Gal-1and Sphingosine-1-phosphate receptor 1 (S1PR1) were determined by immunohistochemistry(IHC) and quantitative real time polymerase chain reaction (qRT-PCR) in GC specimens. Stably transfected Gal-1 or S1PR1 into SGC7901 and MGC-803 cells, western blot and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. RESULTS: Overexpression of Gal-1 enhanced expression of S1PR1 in SGC-7901 cells, and increased cell invasion, while knockdown Gal-1 in MGC-803 cells reduced S1PR1 expression and diminished invasion. Simultaneous knockdown of Gal-1 and overexpression of S1PR1 in MGC803 cells rescued invasive ability of MGC803 cells. S1PR1 was associated with expression of epithelial-to-mesenchymal transition (EMT) markers in vitro and in clinical samples. EMT induced in MGC-803 cells by TGF-ß1 was accompanied by S1PR1 activation, while knockdown of S1PR1 reduced response to TGF-ß1, suggest that Gal-1 promotes GC invasion by activating EMT through a S1PR1-dependent mechanism. Overexpression of S1PR1 promoted subcutaneous xenograft growth and pulmonary metastases, and enhanced expression of EMT markers. CONCLUSION: Galectin-1 promotes metastasis in gastric cancer through a S1PR1- dependent mechanism, our results indicate that targeting S1PR1 may be a novel strategy to treat GC metastasis.

Zusanli (ST36) Acupoint Injection with Neostigmine for Paralytic Postoperative Ileus following Radical Gastrectomy for Gastric Cancer: a Randomized Clinical Trial.

Background: The Zusanli (ST36) acupoint has been associated with treatment of various gastrointestinal conditions. There have been no studies of acupuncture therapy for paralytic postoperative ileus (PPOI). Materials and methods: Patients with PPOI following gastrectomy for gastric cancer were randomized to receive ST36 acupoint injection with neostigmine, gluteal intramuscular injection with 1.0 mg neostigmine, ST36 acupuncture alone, or standard therapy. The main outcome was the effectiveness rate for recovery of peristalsis. Secondary outcomes were time to bowel sound recovery, time to first flatus, and time to first defecation. Tertiary outcomes were drug-related adverse events, including abdominal pain, diarrhea, nausea, vomiting, tearing, delirium, seizure, and anxiety. Results: ST36 acupoint injection with neostigmine and gluteal intramuscular injection of neostigmine gave a higher rate of peristalsis recovery, and the ST36 acupoint injection group showed significantly higher total effectiveness rate than that of the intramuscular injection group. These interventions gave significantly shorter times to bowel sound recovery, shorter times to first flatus and first defecation compared with ST36 acupuncture and standard post-operative therapy (P < 0.01). ST36 acupoint injection group gave shorter time to bowel sound recovery, shorter time to first flatus and first defecation than those of the intramuscular injection group (P < 0.01). Drug-related adverse events in the intramuscular injection group were more serious than in the ST36 acupoint injection group (P < 0.05). Conclusion: ST36 acupoint injection with neostigmine is safe and effective for treatment of PPOI.

Prognostic significance of galectin-1 and vasculogenic mimicry in patients with gastric cancer.

INTRODUCTION: We evaluated the expression of galectin-1 (Gal-1) and vasculogenic mimicry (VM) in gastric cancer (GC) and investigated their relationships with the clinicopathological factors and prognostic significance in GC. MATERIALS AND METHODS: Immunohistochemical (IHC) staining and CD34-periodic acid-Schiff double stain were used to investigate Gal-1 expression and VM in paraffin-embedded sections from 127 patients with GC of all tumor stages. The relationships between Gal-1 expression and VM, clinicopathological variables, and survival were analyzed. P < 0.05 was considered statistically significant. RESULTS: Among the 127 cases, 86 (67.7%) were positive for Gal-1; VM was detected in 29 cases (22.8%). There was a significant association between VM and the Gal-1 IHC staining; all cases with VM were positive for Gal-1 staining. Gal-1 expression and VM in primary GC tissue were associated with tumor size, differentiation, depth of tumor invasion, stage, lymph node metastases, and tumor emboli in microvessels (all, P < 0.05). Kaplan-Meier analysis revealed that the overall survival time was 52.56 ± 2.44 months (95% confidence interval [CI]: 47.77-57.35) for patients with Gal-1-negative and VM-negative primary GC tissue, 43.83 ± 2.17 months (95% CI: 39.58-48.08) for patients with Gal-1-positive but VM-negative primary GC tissue, and 23.97 ± 2.44 months (95% CI: 19.18-28.76) for patients with Gal-1-positive and VM-positive primary GC tissue (χ2 = 60.21, P < 0.01). Gal-1 expression was positively associated with VM in primary GC tissue. CONCLUSION: Both Gal-1 expression and VM in primary GC tissue are indicators of poor prognosis for GC after gastrectomy, and Gal-1 may be a novel target for treating VM in GC.

[Clinical study of preserving left colic artery during laparoscopic total mesorectal excision for the treatment of rectal cancer].

OBJECTIVE: To evaluate the feasibility, safety, radicality and short-term outcome of preserving left colic artery (LCA) during laparoscopic total mesorectal excision (TME) for the treatment of rectal cancer. METHODS: From January 2013 to December 2016,136 patients with mid-lower rectal cancer received laparoscopic TME in the Gastrointestinal Surgery Department of Taizhou People's Hospital of Jiangsu Province. Patients with rectal tumor within 10 cm to the anal verge were enrolled into the study. All the enrolled patients had complete data of pathology and follow-up. Those receiving neoadjuvant chemoradiotherapy, with severe base diseases, multifocal tumor, tumor invasion of surrounding tissues, fixation of tumor, recurrent tumor, complications such as acute ileus, bleeding, perforation were excluded. In this study, 72 patients did not undergo preservation of LCA (high ligation group) and 64 patients underwent preservation of LCA (low ligation group). Operative parameters, clinicopathological data and short-term outcome were collected and compared between two groups. RESULTS: The baseline data including gender, age, body mass index, tumor stage, and distance of tumor from anal verge of two groups were comparable (P>0.05). The differences between two groups about the mean time of operation and the operative blood loss were not significant [(164.0±12.6) min vs. (167.3±9.4) min, (30.0±3.6) ml vs. (30.1±3.0) ml, all P>0.05]. There was no operative death in both groups. Differences in the lymph node dissection (13.7±2.6 vs. 13.3±2.1) and the specimen length of proximal resection margin [(16.4±1.9) cm vs. (16.7±2.1) cm] or distal resection margins [(3.9±0.6) cm vs. (4.1±0.9) cm] between high and low ligation groups were not significant (all P>0.05). Compared with high ligation group, the low ligation group had higher rate of sphincter preservation [92.2% (59/64) vs. 79.2% (57/72), χ2=4.580, P=0.032], lower rate of anastomotic leakage [1.6% (1/64) vs. 9.7% (7/72), χ2=4.075, P=0.044], anastomotic stenosis [3.1% (2/64) vs. 12.5%(9/72), χ2=4.006, P=0.045], and voiding and sexual dysfunction [6.3%(4/64) vs. 18.1%(13/72), χ2=4.317, P=0.038]. Mean time of follow-up was 19 months. In high ligation group, the local recurrent rate was 5.56%, distant metastasis rate was 13.89%, overall survival rate was 90.28%, disease-free survival rate was 80.56%, while in low ligation group, the local recurrence rate was 4.69%, distant metastasis rate was 12.50%, overall survival rate was 90.63%, disease-free survival rate was 82.81%, whose differences between two groups were not significant (all P>0.05). CONCLUSION: Preservation of LCA during laparoscopic TME for the treatment of rectal cancer is safe and feasible, which can reduce the incidence of anastomotic leakage and stenosis, and voiding and sexual dysfunction.

miR-7 Increases Cisplatin Sensitivity of Gastric Cancer Cells Through Suppressing mTOR.

MicroRNAs have been reported to play an important role in diverse biological processes and cancer progression. MicroRNA-7 has been observed to be downregulated in human gastric cancer tissues, but the function of microRNA-7 in gastric cancer has not been well investigated. In this study, we demonstrate that the expression of microRNA-7 was significantly downregulated in 30 pairs of human gastric cancer tissues compared to adjacent normal tissues. Enforced expression of microRNA-7 inhibited cell proliferation and migration abilities of gastric cancer cells, BGC823 and SGC7901. Furthermore, microRNA-7 targeted mTOR in gastric cancer cells. In human clinical specimens, mTOR was higher expressed in gastric cancer tissues compared with adjacent normal tissues. More interestingly, microRNA-7 also sensitizes gastric cancer cells to cisplatin (CDDP) by targeting mTOR. Collectively, our results demonstrate that microRNA-7 is a tumor suppressor microRNA and indicate its potential application for the treatment of human gastric cancer in future.

[Clinical significance of No.12 lymph node dissection for advanced gastric cancer].

OBJECTIVE: To evaluate the clinical significance of No.12 lymph node dissection for advanced gastric cancer with D2 lymphadenectomy. METHODS: Clinicopathologic data and No.12 lymph node dissection of 256 advanced gastric cancer patients undergoing radical operation in our department between January 2005 and December 2010 were retrospectively summarized and the influence factors of metastasis in No.12 lymph nodes were analyzed. RESULTS: Of 256 patients, 179 were male and 77 were female with the average age of 59.2 years. Tumor located in the upper of stomach in 24 cases, middle of stomach in 41 cases, lower of stomach in 174 cases, multi-focus or diffuse distribution of stomach in 17 cases. Tumor diameter was <3 cm in 39 cases, 3 to 5 cm in 100 cases, >5 cm in 117 cases. Serum carcinoembryonic antigen (CEA) level increased in 61 cases, serum carbohydrate antigens (CA)72-4 increased in 56 cases and CA19-9 increased in 61 cases. The number of No.12 lymph nodes resected from all the patients was 1 152, and the average number was 4.5±1.9. The metastasis rate of No.12 lymph nodes was 9.4%(24/256) after hematoxylin eosin staining (positive group). All the patients received effective follow-up to December 2015, and the average follow-up time was 101.2 months. The median survival time of positive No.12 group (24 cases) was 29.8 months and of negative No.12 group (232 cases) was 78.2 months, whose difference was statistically significant (χ2=21.715, P=0.000). Univariate analysis found that No.12 lymph node metastasis was not associated with age, gender, tumor differentiation (all P>0.05), but was associated with tumor location, tumor diameter, invasive depth (all P<0.05), and was closely associated with Borrmann type, outside metastatic lymph nodes of No.12 and high levels of serum CEA, CA72-4 and CA19-9 (all P=0.000). Multivariate regression analysis found that tumor location (RR=2.452, 95%CI:1.537 to 3.267, P=0.000), Borrmann type (RR=1.864, 95%CI:1.121 to 3.099, P=0.016) and number of outside metastatic lymph nodes of No.12 (RR=2.979, 95%CI: 2.463 to 3.603, P=0.000) were the independent risk factors of the No.12 metastasis (P<0.05). CONCLUSIONS: Metastasis in No.12 lymph nodes indicates poorer prognosis. The No.12 lymph nodes of advanced gastric cancer patients with curative resection, especially those with the tumor located in the lower part, Borrmann type IIII(, outside metastatic lymph nodes of No.12, should be regularly cleaned.