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The current treatment strategy for rectal cancer is a comprehensive treatment centered on surgery. The application of total mesorectal excision (TME) has significantly reduced the local recurrence rate and improved the survival prognosis, but a series of pelvic organ dysfunction caused by pelvic autonomic nerve injury during the operation will reduce the postoperative quality of life of patients. Pelvic autonomic nerve preserving (PANP) radical proctectomy has emerged, but the biggest challenge in the implementation process of this technology is the accurate identification of nerves. A series of studies have shown that pelvic intraoperative autonomic monitoring (pIONM) can effectively assist surgeons to identify nerves, The purpose of this article is to introduce the function of pelvic autonomic nerve, the clinical manifestation of postoperative pelvic dysfunction and its relationship with nerve injury, the key points of implementing PANP, and the current situation and research progress of pIONM technology application.

Background: Malnutrition is common in colorectal cancer patients. Malnutrition is recognized as a risk factor for adverse postoperative outcomes, yet there are no consistent diagnostic criteria for it. Thus, the Global Leadership Initiative on Malnutrition published new universal criteria. We aimed to investigate the prevalence of malnutrition with the application of Global Leadership Initiative on Malnutrition criteria, and explore the correlations between Global Leadership Initiative on Malnutrition-defined malnutrition and postoperative clinical outcomes in colorectal cancer patients., Methods: We included a cohort of 918 patients who underwent radical resection surgery for colorectal cancer from July 2014 to October 2019. Malnutrition was diagnosed based on the Global Leadership Initiative on Malnutrition criteria. The associations between nutritional status and postoperative clinical outcomes were analyzed by the Kaplan-Meier method, logistic and Cox regression analyses., Results: Among the included patients, 23.6% were diagnosed as malnutrition based on Global Leadership Initiative on Malnutrition criteria. Global Leadership Initiative on Malnutrition-defined malnutrition was associated with total postoperative complications [odds ratio: 1.497 (1.042-2.152), P = 0.029]. Further, Global Leadership Initiative on Malnutrition-diagnosed malnutrition was an independent risk factor for overall survival [hazard ratio: 1.647 (1.048-2.587), P = 0.030] and disease-free survival [hazard ratio: 1.690 (1.169-2.441), P = 0.005]., Conclusions: The Global Leadership Initiative on Malnutrition criteria is effective to assess malnutrition. Preoperative malnutrition is associated with postoperative complications, overall survival and disease-free survival in colorectal cancer patients after radical resection surgery., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Patients with gastric cancer after gastrectomy often suffer from a decline in their quality of life (QoL), but the relationship between body composition (BC) and physical function on QoL has rarely been studied. This study aims to evaluate and determine the changes in QoL after gastrectomy and the impact of BC and physical function on QoL., Methods: A total of 311 gastric cancer patients completed EORTC QLQ-C30 and EORTC QLQ-STO22 questionnaires before and 1, 3, 6 months post-surgery. Data including BC, handgrip strength (HGS) and 6-m gait speed (GS) were collected prospectively. Multiple linear regression analysis was used to determine the correlation between QoL and BC, HGS and GS., Results: Patients had significantly worse scores after surgery on most function and symptom scales ( p < 0.001), but most of these scales recovered within 6 months after surgery. A higher subcutaneous fat area (SFA)was associated with increased symptom scores 1 month after surgery. A higher GS is associated with a better global health status symptom., Conclusion: Patients suffer from a decline in their QoL after gastrectomy for gastric cancer. Intervention strategies aiming at reducing SFA and improving GS may improve the QoL in patients underwent gastrectomy for gastric cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Song, Huang, Luo, Cai, Yan, Chen, Xing, Dong and Chen.)

Despite the amazing progress in the treatment of gastric cancer (GC), it is still the third leading cause of cancer death in the world. This study explored the key genes that are related to the prognosis and pathogenesis of GC. Data from the cancer genome atlas (TCGA) and Oncomine were applied to evaluate the expression of cystatin 2 (CST2) in GC samples. Kaplan-Meier plotter was carried out to detect the overall survival of GC patients with different expression levels of CST2. Gene Set Enrichment Analysis (GSEA) was carried out to investigate the functions and pathways connected with CST2 expression. Quantitative real-time polymerase chain reaction (qPCR) and Western blot assays were used to assess CST2 expression. The biological properties of GC cells were assessed with the support of cell proliferation and Transwell assays. Important proteins involved in the regulation of CST2 in GC cell behaviors were evaluated by Western blot. Through analysis of the database, we found that CST2 expression was significantly upregulated in GC samples and actively related to GC patients' poor outcomes. Importantly, the analysis of GSEA showed that GST2 expression was closely connected with the proliferation and migration of cells, as well as the TGF-β1 signaling pathway. In addition, biological assays illustrated that over-expression of CST2 strengthened the activity and metastasis of GC cells. After the upregulation of CST2, the expression of cyclin D1, N-cadherin, vimentin, TGF-β1, and Smad4 increased, and E-cadherin expression decreased. Our findings revealed that over-expression of CST2 enhanced the growth, migration, and invasion of GC cells through modulating the epithelial-mesenchymal transition (EMT) and TGF-β1 signaling pathway, affording a possible biomarker for the treatment of GC., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

Objective: To provide biomarkers related to the radiation response of patients to avoid unnecessary side effects on those who were not sensitive to radiotherapy., Patients and Methods: In the present study, we compared the different four proteins (PDIA3, Vimentin, Galectin3, Dhe3) patterns in rectal tumor tissue before and after radiation therapy by using 2-D PAGE, mass spectrometry, and bioinformatics analysis., Results: The protein level of Galectin3 and PDIA3 were downregulated in rectal cancer patients before and after radiotherapy (1.42 folds); while Dhe3 protein and Vimentin were upregulated (1-2 folds), and we also revealed Vimentin as its role in the negative regulation of the well-known transcription factor ATF4., Conclusions: Our study showed that four candidate proteins, including PIDA3, Galectin3, Dhe3, and Vimentin, might be the potential biomarkers in the identification of radiation response in rectal cancer.

Introduction: Parastomal hernia is a common complication after stoma formation. The definitive risk factors for parastomal hernia development remain unclear., Aim: This study evaluated the risk factors through computed tomography (CT) scan of patients with parastomal hernia., Material and Methods: All patients who underwent an operation at our institution from January 2008 to February 2014 were included. We recorded patient-related and operation-related variables, and CT scans were checked. All the variables were analyzed with SPSS 19 to identify the risk factors for parastomal hernia formation., Results: Of the 128 patients who underwent colostomy, 49 (38.3%) developed a parastomal hernia during a median follow-up period of 20.1 months (range: 4-84 months). Hernia development was significantly associated with the thickness of subcutaneous fat in the abdominal wall, the location of the stoma, anteroposterior diameter and horizontal diameter of the body. The defect size of the abdominal wall is another risk factor. The larger the defect size of the abdominal wall, the larger is the parastomal stoma (3.79 ±1.51 vs. 2.13 ±0.74 cm horizontally and 4.90 ±2.25 vs. 2.94 ±0.73 cm vertically, p < 0.001). The hernia contents protrude into the hernial sac through the path of the inner side more than the outer side (77.6% vs. 12.2%)., Conclusions: Our findings in Chinese patients with parastomal hernia match those from Western countries: obesity, the location of the stoma, and the defect size of the abdominal wall are significant risk factors for parastomal hernia formation. The mesenteric region is a weak area, which is a site prone to parastomal hernia, and should be protected., Competing Interests: The authors declare no conflict of interest.

The distribution of peripheral blood lymphocyte subsets were compared between patients with colorectal cancer and healthy controls. The number of natural killer(NK) cells and CD(8)(+)T cells and the percentage of naive CD(4)(+) T cells were all decreased significantly in patients. On the contrary, the percentages of memory CD(4)(+) T cells, HLA-DR(+) CD(8)(+) T cells and CD(38)(+) CD(8)(+) T cells were significantly increased. It suggests that the tumor killing effect of cytotoxic lymphocytes in peripheral blood is impaired in patients with colorectal cancer, whereas the immune response is over stimulated.

Background: PSMA expression in the prostate epithelium is controlled by a cis-element, PSMA enhancer (PSME). PSME contains multiple binding sites for Sox proteins, and in this study, we identified Sox7 protein as a negative regulator of PSMA expression through its interaction with PSME., Methods: The statistical correlation between Sox7 and PSMA mRNA expression was evaluated using five prostate cancer studies from cBioportal. In vitro and in vivo interaction between Sox7 and PSME was evaluated by chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), and luciferase reporter assay. Synthetic oligonucleotides were generated to define the sites in PSME that interact with Sox7 protein. Sox7 mutants were generated to identify the region of this protein required to regulate PSMA expression. Sox7 was also stably expressed in LNCaP/C4-2 and 22Rv1 cells to validate the regulation of PSMA expression by Sox7 in vivo., Results: Sox7 mRNA expression negatively correlated with PSMA/FOLH1 and PSMAL/FOLH1B mRNA expression in Broad/Cornell, TCGA and MSKCC studies, but not in two studies containing only metastatic prostate tumors. PC-3 cells mostly expressed the 48.5 KDa isoform 2 of Sox7, and the depletion of this isoform did not restore PSMA expression. Ectopic expression of canonical, wild-type Sox7 in C4-2 and 22Rv1 cells suppressed PSMA protein expression. ChIP assay revealed that canonical Sox7 protein preferentially interacts with PSME in vivo, and EMSA identified the SOX box sites #2 and #4 in PSME as required for its interaction. Sox7 was capable of directly binding to PSME and suppressed PSME-mediated transcription. The NLS regions of Sox7, but not its β-catenin interacting motif, are essential for this suppressing activity. Furthermore, restoration of wild-type Sox7 expression but not Sox7-NLS mutant in Sox7-null prostate cancer cell lines suppressed PSMA expression., Conclusions: The inactivation of canonical Sox7 is responsible for the upregulated expression of PSMA in non-metastatic prostate cancer., (© 2018 Wiley Periodicals, Inc.)

Objective: Cell autophagy reduces the sensitivity of cancer cells to therapeutic reagents in various types of human cancer. Therefore, the aim of our study was to use human colorectal cancer HCT116 cells to explore whether inhibition of autophagy by 3-Methyladenine (3-MA, an autophagy inhibitor) is able to enhance hypoxia-induced apoptosis in vitro., Materials and Methods: HCT116 cells were treated with 3-MA, hypoxia, or 3-MA plus hypoxia, and the autophagy, apoptosis and proliferation of the HCT116 cells were investigated. Western blot analysis was used to detect autophagy specificity protein microtubule-associated protein light chain 3 (LC3) expression. Effects on apoptosis were evaluated by using flow cytometry (JC-1 staining to measure mitochondrial membrane potential) and annexin V-propidium iodide (PI) staining., Results: The results showed that the treatment of HCT116 cells in vitro with hypoxia alone increased autophagy as well as apoptosis, whereas combination treatment with 3-MA and hypoxia markedly inhibited hypoxia-induced autophagy, but increased hypoxia-induced cell apoptosis., Conclusions: Autophagy might play a role as a self-defense mechanism in hypoxia-treated colon cancer cells, and its inhibition could be a promising strategy for the adjuvant chemotherapy of colon cancer.

Background/aims: Bromodomain-containing protein 4 (BRD4) and phosphatidylinositol 3-kinase (PI3K) are key oncogenic cascades in colorectal cancer (CRC). SF1126 is a novel and potent PI3K-BRD4 dual inhibitor., Methods: CRC cells and human colon epithelial cells were treated with SF1126. Cell survival was tested by MTT and soft agar colony formation assays. Cell proliferation was tested by BrdU ELISA method. Cell apoptosis was tested by a TUNEL staining method and Histone DNA ELISA. Western blotting was utilized to test the signaling proteins. A HT-29 xenograft mice model was established to study the anti-tumor activity of SF1126 in vivo., Results: SF1126 potently inhibited the survival, proliferation, and progression of the cell cycle in an established CRC cell line (HT-29) and primary human colon cancer cells. Significant activation of apoptosis was detected in SF1126-treated CRC cells. In CRC cells, SF1126 blocked Akt-mammalian target of rapamycin (mTOR) complex1/2 signaling and downregulated BRD4 target proteins (Myc and cyclin D1). Further studies showed that SF1126 activated p38 signaling in CRC cells. In contrast, the p38 inhibitors or p38 short hairpin RNA inhibited SF1126-induced cytotoxicity and apoptosis in CRC cells. In vivo, subcutaneous administration of SF1126 significantly inhibited HT-29 xenograft tumor growth in nude mice., Conclusion: SF1126 inhibits CRC cell growth possibly by targeting PI3K-Akt-mTOR, BRD4, and p38 signaling., Competing Interests: The authors declare that no conflicts of interest exist., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

The p53-inducible gene 3 (PIG3) is one of the p53-induced genes at the onset of apoptosis, which plays an important role in cell apoptosis and DNA damage response. Our previous study reported an oncogenic role of PIG3 associated with tumor progression and metastasis in non-small cell lung cancer (NSCLC). In this study, we further analyzed PIG3 mRNA expression in 504 lung adenocarcinoma (LUAD) and 501 lung squamous cell carcinoma (LUSC) tissues from The Cancer Genome Atlas database and we found that PIG3 expression was significantly higher in LUAD with lymph node metastasis than those without, while no difference was observed between samples with and without lymph node metastasis in LUSC. Gain and loss of function experiments were performed to confirm the metastatic role of PIG3 in vitro and to explore the mechanism involved in its oncogenic role in NSCLC metastasis. The results showed that PIG3 knockdown significantly inhibited the migration and invasion ability of NSCLC cells, and decreased paxillin, phospho-focal adhesion kinase (FAK) and phospho-Src kinase expression, while its overexpression resulted in the opposite effects. Blocking FAK with its inhibitor reverses PIG3 overexpression-induced cell motility in NSCLC cells, indicating that PIG3 increased cell metastasis through the FAK/Src/paxillin pathway. Furthermore, PIG3 silencing sensitized NSCLC cells to FAK inhibitor. In conclusion, our data revealed a role for PIG3 in inducing LUAD metastasis, and its role as a new FAK regulator, suggesting that it could be considered as a novel prognostic biomarker or therapeutic target in the treatment of LUAD metastasis., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Escin, a triterpene saponin isolated from horse chestnut seed, has been used to treat encephaledema, tissue swelling and chronic venous insufficiency. Recent studies show that escin induces cell cycle arrest, tumor proliferation inhibition and tumor cell apoptosis. But the relationship between escin-induced DNA damage and cell apoptosis in tumor cells remains unclear. In this study, we investigated whether and how escin-induced DNA damage contributed to escin-induced apoptosis in human colorectal cancer cells. Escin (5-80 μg/mL) dose-dependently inhibited the cell viability and colony formation in HCT116 and HCT8 cells. Escin treatment induced DNA damage, leading to p-ATM and γH2AX upregulation. Meanwhile, escin treatment increased the expression of p62, an adaptor protein, which played a crucial role in controlling cell survival and tumorigenesis, and had a protective effect against escin-induced DNA damage: knockdown of p62 apparently enhanced escin-induced DNA damage, whereas overexpression of p62 reduced escin-induced DNA damage. In addition, escin treatment induced concentration- and time-dependent apoptosis. Similarly, knockdown of p62 significantly increased escin-induced apoptosis in vitro and produced en escin-like antitumor effect in vivo. Overexpression of p62 decreased the rate of apoptosis. Further studies revealed that the functions of p62 in escin-induced DNA damage were associated with escin-induced apoptosis, and p62 knockdown combined with the ATM inhibitor KU55933 augmented escin-induced DNA damage and further increased escin-induced apoptosis. In conclusion, our results demonstrate that p62 regulates ATM/γH2AX pathway-mediated escin-induced DNA damage and apoptosis.

Background: Recent studies have shown that laminin subunit alpha 4 (LAMA4) plays an important role in carcinogenesis. However, its molecular biological function in triple-negative breast cancer (TNBC) has not been entirely clarified. This study investigated the expression of LAMA4 in TNBC and its effect on cell proliferation, migration and invasion. Furthermore, we also identified the potential miRNA directly targeting LAMA4., Methods: Western blot, Real-time quantitative PCR (qPCR) and immunohistochemical staining (IHC) were used to detect the expression of LAMA4 in TNBC. The effects of LAMA4 on TNBC cell proliferation, migration and invasion were also explored in vitro. The potential miRNA that targets LAMA4 was determined by dual luciferase reporter assay and verified by qPCR and western blot analysis., Results: Our study showed LAMA4 mRNA (p = 0.001) and protein (p = 0.005) expression in TNBC tissue samples were elevated compared with adjacent normal tissue samples, and LAMA4 was mainly expressed in the cytoplasm of breast carcinoma cells. Knockdown of LAMA4 inhibited TNBC cell proliferation, migration and invasion in vitro. Moreover, further study revealed that LAMA4 was a putative target of miR-539, and miR-539 negatively regulated LAMA4 expression by directly targeting its 3'-UTR., Conclusions: Our study suggested that miR-539 suppressed the expression of LAMA4. LAMA4 plays an important role in tumor progression and may be an important target in treatment of TNBC.

The objective of this work was to develop a simple, selective, and sensitive LC-MS/MS method for the quantitation of the mepivacaine in Chinese biological matrix. The calibration curve of mepivacaine ranged from 0.5 to 2000 ng/mL with the lower limit of quantitation being 0.5 ng/mL. This sensitivity was high enough to describe the profile of blood mepivacaine level versus time. Thereby it was very desirable for the pharmacokinetic study because of its high sensitivity and accuracy. The study used a single-dose two-period crossover design principle. For the pharmacokinetic analysis of plasma, the mean (SD) values obtained were as follows: t 1/2 , 1.63 (0.43) h; C max , 435.3 (67.4) ng/ml; AUC 0-t , 1546.9 (339.7) ng/ml·h; AUC 0-∞ , 1982.3 (421.4) ng/ml·h; T max , 0.62 (0.31) h. The validated method has been successfully applied to assess the pharmacokinetic study of mepivacaine after a single administration to Chinese volunteers.

Aim: To assess the efficacy of a modified approach with transanal total mesorectal excision (taTME) using simple customized instruments in male patients with low rectal cancer., Methods: A total of 115 male patients with low rectal cancer from December 2006 to August 2015 were retrospectively studied. All patients had a bulky tumor (tumor diameter ≥ 40 mm). Forty-one patients (group A) underwent a classical approach of transabdominal total mesorectal excision (TME) and transanal intersphincteric resection (ISR), and the other 74 patients (group B) underwent a modified approach with transabdominal TME, transanal ISR, and taTME. Some simple instruments including modified retractors and an anal dilator with a papilionaceous fixture were used to perform taTME. The operative time, quality of mesorectal excision, circumferential resection margin, local recurrence, and postoperative survival were evaluated., Results: All 115 patients had successful sphincter preservation. The operative time in group B (240 min, range: 160-330 min) was significantly shorter than that in group A (280 min, range: 200-360 min; P = 0.000). Compared with group A, more complete distal mesorectum and total mesorectum were achieved in group B (100% vs 75.6%, P = 0.000; 90.5% vs 70.7%, P = 0.008, respectively). After 46.1 ± 25.6 mo follow-up, group B had a lower local recurrence rate and higher disease-free survival rate compared with group A, but these differences were not statistically significant (5.4% vs 14.6%, P = 0.093; 79.5% vs 65.1%, P = 0.130)., Conclusion: Retrograde taTME with simple customized instruments can achieve high-quality TME, and it might be an effective and economical alternative for male patients with bulky tumors., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest.

Here, we assessed the anti-colorectal cancer (CRC) cell activity of cinobufagin (CBG). We found that CBG exerted potent cytotoxic and anti-proliferative activity against CRC lines (HCT-116 and HT-29) and primary human CRC cells. Meanwhile, it activated apoptosis, and disrupted cell-cycle progression in the cells. At the signaling level, CBG treatment in CRC cells provoked endoplasmic reticulum stress (ER stress), the latter was evidenced by caspase-12 activation, CHOP expression, as well as PERK and IRE1 phosphorylations. Contrarily, the ER stress inhibitor salubrinal, the caspase-12 inhibitor and CHOP shRNA remarkably attenuated CBG-induced CRC cell death and apoptosis. Further, CBG in-activated mammalian target or rapamycin complex 1 (mTORC1), which appeared responsible for proliferation inhibition in CRC cells. Introduction of a constitutively-active S6K1 ("ca-S6K1") restored proliferation of CBG-treated CRC cells. Finally, CBG intraperitoneal injection suppressed HCT-116 xenograft tumor growth in the nude mice. CHOP upregulation and mTORC1 in-activation were also noticed in CBG-treated HCT-116 tumors. The results of this preclinical study suggest that CBG could be tested as promising anti-CRC agent.

Background: Circulating cell-free DNA (ccf-DNA) in plasma may contain both specific and non-specific of tumor markers. The concentration and integrity of ccf-DNA may be clinical useful for detecting and predicting cancer progression., Methods: Plasma samples from 40 healthy controls and 73 patients with gastric cancers (two stage 0, 17 stage I, 11 stage II, 33 stage III, and 10 stage IV according to American Joint Committee on Cancer stage) were assessed respectively. qPCR targeting the Alu repeats was performed using two different sets of primers amplifying the long and short segments. DNA integrity was calculated as a ratio of the long to the short fragments of Alu repeats., Results: Plasma DNA concentration was significantly higher in patients with stage III and IV gastric cancers than in healthy controls (p = 0.028 and 0.029 respectively). The receiver operating characteristic (ROC) curve for discriminating patients with stage III and IV gastric cancers from healthy controls had an area under the curve (AUC) of 0.744 (95% CI, 0.64 to 0.85). Circulating cell-free DNA concentration increased within 21 days following surgery and dropped by 3 months after surgery., Conclusions: Concentration of ccf-DNA is a promising molecular marker for assessing gastric cancer progression., Trial Registration: Current Controlled Trials ChiCTR-DDT-12002848 , 8 October 2012.

The gastrointestinal tract, especially the small intestine, is particularly sensitive to radiation, and is prone to radiation-induced injury as a result. Neurogenic differentiation factor (NeuroD) is an evolutionarily-conserved basic helix-loop-helix (bHLH) transcription factor. NeuroD contains a protein transduction domain (PTD), which allows it to be exogenously delivered across the membrane of mammalian cells, whereupon its transcription activity can be unleashed. Whether NeuroD has therapeutic effects for radiation-induced injury remains unclear. In the present study, we prepared a NeuroD-EGFP recombinant protein, and explored its protective effects on the survival and intestinal damage induced by ionizing radiation. Our results showed that NeuroD-EGFP could be transduced into small intestine epithelial cells and tissues. NeuroD-EGFP administration significantly increased overall survival of mice exposed to lethal total body irradiation (TBI). This recombinant NeuroD also reduced radiation-induced intestinal mucosal injury and apoptosis, and improved crypt survival. Expression profiling of NeuroD-EGFP-treated mice revealed upregulation of tissue inhibitor of metalloproteinase 1 (TIMP-1), a known inhibitor of apoptosis in mammalian cells. In conclusion, NeuroD confers protection against radiation-induced intestinal injury, and provides a novel therapeutic clinical option for the prevention of intestinal side effects of radiotherapy and the treatment of victims of incidental exposure.

Tumor‑associated macrophages (TAMs), a major component of the tumor microenvironment, are crucial to the processes of tumor growth, infiltration and metastasis, and contribute to drug resistance. The importance of TAMs in radiation resistance of colorectal cancer remains unclear. To investigate the effects of autophagy regulation of TAMs on the radiosensitivity of colorectal cancer cells, the current study induced TAM formation from THP‑1 monocyte cells. Sequential treatment of THP‑1 cells with PMA for 72 h and human recombinant interleukin‑4 for 24 h was used to stimulate THP‑1 differentiation to TAMs. Expression of the cell surface markers CD68, CD204 and CD206, and changes to cell morphology were used to confirm successful differentiation. The TAMs were stimulated to promote or inhibit autophagy during co‑culture with LoVo colorectal adenocarcinoma cells. The cells were irradiated, with subsequent measurement of LoVo colony formation and apoptosis. Additionally, the expression of p53, Bcl‑2, survivin and Smac proteins was assessed by western blotting. Monodansylcadaverin staining was used to analyze the presence of autophagic vacuoles in TAM, and western blot analysis was used to assess the expression of Beclin‑1, LC3B I and II, ATG‑3, ‑5 and ‑7. The results demonstrated TAM autophagy to be markedly altered by rapamycin and bafilomycin A1 treatment. Following co‑culture with TAMs, the colony formation rate and survival fraction of LoVo cells were significantly higher than those in the control group (P<0.05). It was further demonstrated that the regulation of autophagy in TAMs was able to inhibit the colony formation of LoVo colorectal cancer cells. Upregulation of TAM autophagy using rapamycin exhibited more effective inhibition of LoVo colony formation than autophagy downregulation. Notably, apoptosis was significantly increased in LoVo cells when co‑cultured with TAMs only, or with rapamycin‑mediated autophagy upregulated TAMs, compared with LoVo cells cultured alone (P<0.01). Expression of Bcl‑2, survivin and p53 were reduced in LoVo cells co‑cultured with TAMs, compared with the control group (P<0.05), whereas Smac expression was increased in the co‑culture groups (P<0.01). It was demonstrated that rapamycin‑mediated autophagy stimulation in TAMs led to reduced expression levels of survivin and Bcl‑2, however, Smac expression was increased. The upregulation of autophagy in TAMs inhibited proliferation and induced apoptosis in colon cancer cells, and altered the expression of radiosensitivity‑associated proteins. This data indicated that the radiosensitivity of colorectal cancer cells is associated with autophagy of TAM, and that stimulating TAM autophagy may increase the radiosensitivity of colorectal cancer cells.

Colorectal cancer (CRC) is still one of the most important neoplasias causing human death. Multidisciplinary therapy has won consensus in the management of CRC, of which, radiotherapy occupies an important position. However, radioresistance is still a major obstacle in local control of CRC. Overexpression of long non-coding RNA HOTAIR has been found to correlate with tumorigenesis and poor prognosis in several types of cancer. In the present study, we analyzed HOTAIR expression levels of 53 CRC patients in tumor and adjacent normal tissue by real-time quantitative PCR. Knockdown of HOTAIR by RNA interference was performed to explore its roles in cell proliferation, migration, invasion, apoptosis and radiosensitivity. Results showed that CRC patients had higher HOTAIR expression in tumor tissues compared with adjacent normal tissues. In vitro, downregulation of HOTAIR reduced proliferation, migration and invasiveness while enhanced apoptosis and radio-sensitivity of CRC cells. Taken together, our findings suggest that long non-coding RNA HOTAIR expression is closely associated with tumor invasion and radiosensitivity, indicating the potential role in diagnostics and therapeutics of CRC.

Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. This study aimed to investigate the radioprotective effects of CAPE on X-ray irradiation induced intestinal injury in rats. Rats were intragastrically administered with 10 μmol/kg/d CAPE for 7 consecutive days before exposing them to a single dose of X-ray irradiation (9Gy) to abdomen. Rats were sacrificed 72 h after exposure to radiation. We found that pretreatment with CAPE effectively attenuated intestinal pathology changes, apoptosis, oxidative stress, bacterial translocation, the content of nitric oxide and myeloperoxidase as well as the concentration of plasma tumor necrosis factor-α. Pretreatment with CAPE also reversed the activation of p38MAPK and the increased expression of intercellular cell adhesion molecule-1 induced by radiation in intestinal mucosa. Taken together, these results suggest that pretreatment with CAPE could be a promising candidate for treating radiation-induced intestinal injury., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The aim of the present study was to investigate the effects of small interfering RNA‑mediated inhibition of Class III phosphoinositide 3‑kinase (PI3K) signal transduction on the proliferation, apoptosis and autophagy of SGC7901 gastric cancer cells. The present study also aimed to examine the contribution of autophagic inhibition to the antitumor effects of 5‑fluorouracil (5‑FU). A PI3K(III)‑RNA interference (i)‑green fluorescent protein (GFP) recombinant replication adenovirus (AD) and the negative control (NC)‑RNAi‑GFP control AD were constructed and infected into SGC7901 cells. A methyl thiazolyl tetrazolium assay was used to determine the growth rate of the SGC7901 cells. Immunofluorescent staining was used to detect microtubule‑associated protein 1 light chain 3 expression. The mitochondrial membrane potential was measured using the JC‑1 fluorescent probe. Autophagic expression was monitored with MDC staining and transmission electron microscopy. The results revealed that following combination treatment of the SGC7901 gastric cancer cells with 5‑FU + PI3K(III)‑RNAi‑AD, the optical density absorbance values at 24, 48 and 72 h were 0.17 ± 1.64, 0.13 ± 4.64 and 0.11 ± 3.56%, respectively, with cell viability inhibition ratios of 45.89 ± 6.67, 72.57 ± 9.48 and 87.51 ± 4.65%, respectively. As compared with the other treatment groups, the inhibition rate in the combined treatment group was significantly higher (P<0.05). The percentages of the cells with green fluorescence in the combined treatment group were 74.4 ± 3.86 (24 h), 82.3 ± 1.84 (48 h) and 92.5 ± 1.1% (72 h), which were larger than those of the other groups. The percentage of cells with green fluorescence became larger, which indicated that the mitochondrion membrane potential had been reduced to a greater extent. MDC staining revealed that the number of autophagic vacuoles in the cells (measured at 24, 48 and 72 h) decreased gradually with time, with more autophagic vacuoles observed in the cells in the control group at 24 h than those in the other treatment groups. Fewest autophagic vacuoles were identified in the combined treatment group. Using a fluorescence microscope, the immune fluorescence expression of microtubule‑associated proteins 1A/1B light chain 3A, which is the specific protein of autophagy, in the combined treatment group was observed to be significantly downregulated, as compared with the other groups. As determined by transmission electron microscopic observation of the SGC7901 gastric cancer cells, the degree of autophagy in the combined treatment group was significantly reduced, as compared with that of the other treatment groups. In conclusion, following combined treatment with 5‑FU and an inhibitor of class III PI3K signal transduction, the proliferation of SGC7901 cells was significantly suppressed, the mitochondrion membrane potentials were significantly reduced and the expression levels of autophagic markers were significantly downregulated.

Objectives: To compare laparoscopic extraperitoneal colostomy with transperitoneal colostomy for construction of a permanent stoma by measuring the incidence of parastomal hernia, and other postoperative complications related to colostomy., Methods: The meta-analysis was carried out in the General Surgery Department of the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China in 2014. A literature search of Medline, EMBASE, Cochrane database, and the Chinese Biomedical Literature Database (CBM) from the years 1990 to 2014 was performed. The literature searches were carried out using medical subject headings and free-text words: extraperitoneal colostomy, transperitoneal colostomy, laparoscopic extraperitoneal colostomy, rectal cancer,  laparoscopic abdominoperineal resection, parastomal hernia, permanent stoma, and colostomy-related complications. Two different reviewers carried out the search and evaluated studies independently., Results: One randomized controlled trial and 6 retrospective studies were included. A total of 378 patients (209 extraperitoneal colostomy and 169 transperitoneal colostomy) were identified. Our analysis showed that there was a significantly lower rate of parastomal hernia (odds ratio 0.10; 95% confidence interval 0.03-0.29, p&lt;0.0001) in the extraperitoneal colostomy group. However, the other stoma-related complications were not significantly different between the 2 groups., Conclusion: Colostomy construction via the extraperitoneal route using a laparoscopic approach can largely reduce the incidence of parastomal hernia. Laparoscopic permanent sigmoid stoma creation through the extraperitoneal route should be the first choice after laparoscopic abdominoperineal resection.

The prognosis of radioresistant colorectal cancer (CRC) is generally poor. Abnormal expression of microRNAs (miRNAs) is involved in the radiosensitivity of various tumor cells as these RNAs regulate biological signaling pathways. However, radioresistance-associated miRNAs in CRC have not yet been identified. In this study, we filtered out HCT116 and CCL-244 from seven CRC cell lines that showed the highest difference in radiosensitivity in a clonogenic assay. MiRNA sequencing identified 33 differentially expressed miRNAs (13 up-regulated and 20 down-regulated) in CCL-244 and 37 in HCT116 (20 up-regulated and 17 down-regulated) cells. MiR-100 was significantly down-regulated in CCL-244 cells after X-ray irradiation but not in HCT116 cells. Quantitative real-time PCR showed that the expression of miR-100 in CRC tissues was significantly lower than that in normal tissues. Thus, miR-100 seems to be involved in the radioresistance of CCL-244 cells. MiR-100 up-regulation sensitized CCL-244 cells to X-ray irradiation, which probably led to apoptosis and DNA double-strand breaks in these. In conclusion, to our knowledge, this is the first study to show that miR-100 may play an important role in regulating the radiosensitivity of CRC, and it may act as a new clinical target for CRC radiotherapy.

The study aimed to investigate the bio-distribution and radio-immuno-imaging features of [(131)I]-herceptin in nude mice with BT-474 breast carcinoma. [(131)I]-Herceptin was administrated by tail intravenous injection to the nude mice with BT-474 breast carcinoma. Radiocounting was performed at 4, 12, 24, 48, and 96 h after administration. The activity ratio in the tumor tissue and non-tumor tissue (T/NT) and the radiocounting percentage per gram tissue to the injected dose (%ID/g) were calculated. The nude mice with BT-474 breast carcinoma were also visualized continuously by single photon emission computed tomography at 2, 4, 8, 12, 24, 48, and 96 h after the injection of [(131)I]-herceptin. Nude mice with MDA-MB-231 used as the control group were subjected to the same analyses. Clear tumor images were obtained after the injection of [(131)I]-herceptin in nude mice with BT-474 breast carcinoma. The images were the clearest at 24 h after the injection and remained clear even at 96 h. The T/NT ratio and %ID/g in the tumor tissues of nude mice with BT-474 were both significantly higher than those of the control group (P < 0.01). [(131)I]-Herceptin displays tumors clearly in the nude mice with BT-474 and accumulates well in the tumor tissues.

The aim of this study was to investigate the effects of the adenoviral-mediated autophagy gene, damage-regulated autophagy regulator (DRAM), on the proliferation and autophagy of SGC7901 human gastric cancer cells in vitro . The recombinant adenovirus, AdMax-pDC315-DRAM-EGFP, working as a virus vector of DRAM was constructed and infected into the SGC7901 human gastric cancer cell line. The MTT assay was used to determine the growth rate of the SGC7901 cells. Activation of autophagy was monitored with monodansylcadaverin (MDC) staining following AdMax-pDC315-DRAM-EGFP treatment. Immunofluorescent staining was used to examine the expression of microtubule-associated protein 1 light chain 3 (LC3), and western blotting was used to examine the expression of apoptosis- and autophagy-associated proteins, including Beclin1, p53, p21 and B-cell lymphoma 2 (Bcl-2), in the culture supernatant. The viability of the SGC7901 cells was activated by AdMax-pDC315-DRAM-EGFP treatment. The AdMax-pDC315-DRAM-EGFP-treated cells exhibited positive LC3 expression detected by immunoreactivity and MDC staining. Inductions in the expression of the apoptosis-related proteins, p53 and p21, and the autophagic protein, Beclin1, were revealed by western blot analysis. By contrast, downregulation of the apoptosis-related protein, Bcl-2, following AdMax-pDC315-DRAM-EGFP treatment was identified. In conclusion, the present study demonstrated that AdMax-pDC315-DRAM-EGFP treatment resulted in upregulation of the level of autophagy and induction of cell proliferation in the SGC7901 human gastric cancer cell line in vitro .

Autophagy, type II nonapoptotic cell death, is characterized by the formation of double-membrane cytosolic vesicles, the recycling of damaged cytoplasmic content and the maintenance of genetic stability and cellular homeostasis, under conditions of nutrient starvation, hypoxia or other therapeutic stress. In the present study, we comprehensively discuss its indispensable role in the formation of vasculogenic mimicry (VM), capillary-like tubes consisting of cells from the tumor itself instead of vascular endothelial cells. A short hairpin RNA (shRNA) to silence beclin1, an autophagy-specific gene, was designed, synthesized and subcloned into a vector to establish an autophagy-inhibited group, while negative control and blank groups were also established using human gastric cancer SGC7901 cells. We then investigated the VM formation ability of these three groups and detected changes in gene expression, survival and invasion correspondingly. The results showed that, following the formation of VM, the expression of pluripotent genes (c-myc, oct3/4, sox-2) and autophagy-specific genes (beclin1, ATG5, ATG7) were increased, which was consistent with the negative control cell group. However, the autophagy inhibited cell group did not form VM, and the expression of pluripotent genes was decreased. Moreover, the inhibition of autophagy reduced the survival and invasive ability of cancer cells under stress. We suggest that during the formation of VM, the stable expression of genes and the maintenance of survival and invasion are indispensable. Under a stress environment, autophagy is activated to maintain the stability of gene expression, maintain survival and invasive ability and facilitate VM formation, which can provide nutrients, oxygen and invasive channels to tumors, facilitating survival and development under stress.

Introduction: In the previous study, we found that the inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 induced SGC7901 cell death in vitro. We did not know whether SN50, which is a specific inhibitor of nuclear factor κB (NF-κB), could increase the cell death induction of gastric cancer of LY294002 in vitro, and we also wanted to know the mechanism of it, which might be applied to clinical tumor therapy., Material and Methods: The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the cytotoxic effects of the drugs. Mitochondrial membrane potential was measured using the fluorescent probe JC-1. Hoechst 33258 staining was used to detect apoptosis and necrosis morphological changes after LY294002 and/or SN50 treatment. Expression of p53, PUMA and Beclin1 were determined with real-time polymerase chain reaction (RT-PCR) analysis. We used transmission electron microscopy to identify ultrastructural changes in SGC7901 cells after LY294002 and/or SN50 treatment., Results: In this study, we found that treating the human gastric cancer cells SGC7901 with SN50 could significantly enhance the effects of LY294002 on inducing cell death after 24 h, compared to the control group (p < 0.05). Detection of mitochondrial potential and transmission electron microscopic examination indicated that the rate of cell death increased progressively. The expression of p53, PUMA and Beclin1 was up-regulated., Conclusions: The NF-κB inhibitor SN50 could enhance the role of LY294002 on inducing cell death of human gastric cancer cells SGC7901, which might be a promising new approach to gastric cancer therapy.

Objective: To compare proximal gastrectomy (PG) with total gastrectomy (TG) for proximal gastric carcinoma, through the 5-year survival rate, recurrence rate, postoperative complications, and long-term life quality., Methods: The meta-analysis was carried out in the General Surgery Department of the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. We searched Medline, EMBASE, and the Cochrane Library from June to November 2012. The literature searches were carried out using medical subject headings and free-text word: `proximal gastrectomy` `total gastrectomy` `partial gastrectomy` `stomach neoplasms` and `gastric cancer`. Two different reviewers carried out the search and evaluated studies independently., Results: Two randomized controlled trials and 9 retrospective studies were included. A total of 1364 patients were included in our study. Our analysis showed that there is no statistically significant difference in 5-year survival rate between PG and TG (60.9% versus 64.4%). But, the recurrence is higher in the PG group than the TG (38.7% versus 24.4%). The anastomotic stenosis rate is also higher in the PG than the TG (27.4% versus 7.4%)., Conclusion: Proximal gastrectomy is an option for upper third gastric cancer in terms of safety. However, it is associated with high risk of reflux symptoms and anastomotic stenosis. Therefore, TG should be the first choice for proximal gastric cancer to prevent reflux symptoms.

Objective: To investigate the correlation of single nucleotide polymorphisms (SNP) of XRCC1 gene to hereditary susceptibility of colorectal cancer., Methods: XRCC1 genotypes in 124 colorectal cancer patients and 214 matched healthy people as control were analyzed by SnaP Shot SNP-typing technique. Five different inheritance models including codominant, dominant, recessive, overdominant and log-additive were analyzed using logistic regression model. The haplotype distribution was estimated with phase and its correlation with the risk of colorectal cancer was evaluated., Results: The frequencies of mutant 25487G-A, 25489C-T and 1799782C-T alleles were 0.20, 0.11, 0.32 respectively in the patients, and 0.23, 0.13, 0.34 in the controls. There was no significant correlation of polymophisms of XRCC1 gene to the risk of colorectal cancer in 5 different inheritance models (P>0.05). GCT, GCC, ACC and GTC were the most common haplotypes and the odds ratios were 1, 1.35, 0.90 and 0.84 respectively. There was no significant difference of distribution between 2 groups in haplotypes., Conclusion: Polymorphisms of XRCC1 gene, including rs25487, rs25489, rs1799782, are not associated with to the risk of colorectal cancer.

Purpose: To study the molecular mechanisms of colorectal cancer liver metastasis., Methods: Cecal wall implantation was performed in nude mice to subclone a highly liver metastatic human colorectal cancer clone (SW1116-M) from SW1116. In vivo and in vitro assays were adopted to confirm the proliferation and metastasis potential. The human tumor metastasis PCR microarrays were used to analyze the differential gene expressions. The results were confirmed further by real-time quantitative PCR., Results: SW1116-M and SW1116-S5, two human colon cancer cell clones with different metastatic potential, were subcloned from SW1116. In SW1116-M, in vitro invasion, migration and in vivo metastatic potential were higher, and in vitro proliferation rate was lower than SW1116-S5. In tumor metastasis PCR microarray, 24 genes related to cell invading, adhesion, cellular growth and differentiation were found with a twofold difference between SW1116-S5 and SW1116-M. Sixteen of these, including E-cadherins, MTSS1, TRAIL and TRPM1, were up-regulated; eight genes including cathepsin L, EphB2, HGF, MET, MCAM and RORβ were down-regulated., Conclusions: We have established a highly liver metastatic clone. The subsequent metastasis PCR microarray analysis identified a procedure of cellular differentiation and mesenchymal to epithelial transition (MET) in liver metastasis. The colonization to from macrometastasis is not a switch from cell cycle arrest but a result of cell differentiation and MET.

Objective: To investigate the effect of recombinant adenovirus (phosphatidylinositol-3-kinases(PI3K)(I()-RNAi-AD which blocks the class I( PI3K signaling pathway on gastric carcinoma cells xenografts in nude mice., Methods: Subcutaneous tumor models of nude mice were established with SGC7901 cells and randomly divided into PI3K(I()-RNAi-AD group, NC-RNAi-GFP-AD group and control group. The tumor size and the inhibitory rate of tumor growth on days 3, 6, and 9 after cell transplantation were measured. The expression of TNF-α, COX2, P53, PCNA, E-cadherin and nm23/DNPK in tumor tissues were detected by immunohistochemistry., Results: Tumor growth was significantly inhibited in the PI3K(I()-RNAi-AD group(14.2%, 21.0%, and 28.1%) on days 3, 6, 9 compared with NC-RNAi-GFP-AD group(1.3%, 1.9%, and 2.0%, all P<0.05). The expressions of TNF-α, P53, E-cadherin and nm23/DNPK were up-regulated, and the expressions of COX2 and PCNA were down-regulated in the PI3K(I()-RNAi-AD group by immunohistochemical staining(all P<0.05)., Conclusions: PI3K(I()-RNAi-AD can inhibit the growth of SGC7901 cell transplantation tumor in vivo in nude mice by inhibiting cell growth, reducing the capacity of tumor invasion and inhibiting tumor angiogenesis.

Aim: To investigate the effects of small interfering RNA (siRNA)-mediated inhibition of Class I phosphoinositide 3-kinase (Class I PI3K) signal transduction on the proliferation, apoptosis, and autophagy of gastric cancer SGC7901 and MGC803 cells., Methods: We constructed the recombinant replication adenovirus PI3K(I)-RNA interference (RNAi)-green fluorescent protein (GFP) and control adenovirus NC-RNAi-GFP, and infected it into human gastric cancer cells. MTT assay was used to determine the growth rate of the gastric cancer cells. Activation of autophagy was monitored with monodansylcadaverine (MDC) staining after adenovirus PI3K(I)-RNAi-GFP and control adenovirus NC-RNAi-GFP treatment. Immunofluorescence staining was used to detect the expression of microtubule-associated protein 1 light chain 3 (LC3). Mitochondrial membrane potential was measured using the fluorescent probe JC-1. The expression of autophagy was monitored with MDC, LC3 staining, and transmission electron microscopy. Western blotting was used to detect p53, Beclin-1, Bcl-2, and LC3 protein expression in the culture supernatant., Results: The viability of gastric cancer cells was inhibited after siRNA targeting to the Class I PI3K blocked Class I PI3K signal pathway. MTT assays revealed that, after SGC7901 cancer cells were treated with adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition reached 27.48% ± 2.71% at 24 h, 41.92% ± 2.02% at 48 h, and 50.85% ± 0.91% at 72 h. After MGC803 cancer cells were treated with adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition reached 24.39% ± 0.93% at 24 h, 47.00% ± 0.87% at 48 h, and 70.30% ± 0.86% at 72 h (P < 0.05 compared to control group). It was determined that when 50 MOI, the transfection efficiency was 95% ± 2.4%. Adenovirus PI3K(I)-RNAi-GFP (50 MOI) induced mitochondrial dysfunction and activated cell apoptosis in SGC7901 cells, and the results described here prove that RNAi of Class I PI3K induced apoptosis in SGC7901 cells. The results showed that adenovirus PI3K(I)-RNAi-GFP transfection induced punctate distribution of LC3 immunoreactivity, indicating increased formation of autophagosomes. The results showed that the basal level of Beclin-1 and LC3 protein in SGC7901 cells was low. After incubating with adenovirus PI3K(I)-RNAi-GFP (50 MOI), Beclin-1, LC3, and p53 protein expression was significantly increased from 24 to 72 h. We also found that Bcl-2 protein expression down-regulated with the treatment of adenovirus PI3K(I)-RNAi-GFP (50 MOI). A number of isolated membranes, possibly derived from ribosome-free endoplasmic reticulum, were seen. These isolated membranes were elongated and curved to engulf a cytoplasmic fraction and organelles. We used transmission electron microscopy to identify ultrastructural changes in SGC7901 cells after adenovirus PI3K(I)-RNAi-GFP (50 MOI) treatment. Control cells showed a round shape and contained normal-looking organelles, nucleus, and chromatin, while adenovirus PI3K(I)-RNAi-GFP (50 MOI)-treated cells exhibited the typical signs of autophagy., Conclusion: After the Class I PI3K signaling pathway has been blocked by siRNA, the proliferation of cells was inhibited and the apoptosis of gastric cancer cells was enhanced.

Background: Apoptosis may be induced after Bcl-2 expression is inhibited in proliferative cancer cells. This study focused on the effect of autophagy activation by ABT737 on anti-tumor effects of epirubicin., Methods: Cytotoxic effects of ABT737 on the HepG2 liver cancer cell line were assessed by MTT assay and cell apoptosis through flow cytometry. Mitochondrial membrane potential was measured by fluorescence microscopy. Monodansylcadaverin (MDC) staining was used to detect activation of autophagy. Expression of p53, p62, LC3, and Beclin1, apoptotic or autophagy related proteins, was detected by Western blotting., Results: ABT737 and epirubicin induced growth inhibition in HepG2 cells in a dose- and time-dependent manner. Both ABT737 and epirubicin alone could induce cell apoptosis with a reduction in mitochondrial membrane potential as well as increased apoptotic protein expression. Further increase of apoptosis was detected when HepG2 cells were co- treated with ABT373 and epirubicin. Furthermore, our results demonstrated that ABT373 or epirubicin ccould activate cell autophagy with elevated autophagosome formation, increased expression of autophagy related proteins and LC3 fluorescent puncta., Conclusions: ABT737 influences cancer cells through both apoptotic and autophagic mechanisms, and ABT737 may enhance the effects of epirubicin on HepG2 cells by activating autophagy and inducing apoptosis.

Objective: To evaluate the recurrence and fecal incontinence of anal fistula plug versus conventional surgical treatment for anal fistulas., Methods: This meta-analysis was carried out in the General Surgery Department of the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. We searched the Medline, EMBASE, and Cochrane Library from June 2011 to April 2012. The literature searches were carried out using medical subject headings and free-text word: anal fistula, fibrin adhesive, fibrin sealant, and fistula plug., Results: Two randomized controlled trials and 3 retrospective controlled studies were included. A total of 428 patients were included in our study. The recurrence rate was higher in those patients who accept fistula plug treatment (62.1% versus 47%) (p=0.004)., Conclusion: Anal fistula plug has a moderate probability of success with little risk of incontinence, but the recurrence rate is significantly higher than the conventional surgical treatment. This treatment is minimally invasive, repeatable, and sphincter-sparing. This meta-analysis failed to find a statistically significant difference in incontinence rate between conservative treatment and conventional surgical treatment.

Objective: To investigate the effects of damage-regulated autophagy modulator (DRAM) on radiosensitivity and the related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice., Methods: Nude mice were randomly divided into model control group, radiotherapy group, and DRAM treatment group and radiotherapy combined with DRAM treatment group. When volume of transplantation tumor were 1.0 cm(3), radiotherapy, DRAM treatment was given. On days 3, 6 and 9 after treatment, the inhibition rate of tumor growth, pathological changes in tumor specimens, expression levels of P53, proliferating cell nuclear antigen(PCNA), C-myc, Fas-L, as well as apoptosis indexes in tumor samples were observed., Results: Inhibition rates of tumor in DRAM combined with radiotherapy were 9.3%, 14.1%, 16.7% on day 3, 6 and 9, respectively, all significantly higher than those in the radiotherapy group(5.0%, 8.8%, 6.5%, P<0.05). The expressions of PCNA and C-myc protein were down-regulated, while the expressions of P53 and Fas-L were upregulated., Conclusion: Damage-regulated autophagy modulator gene may promote cell apoptosis and inhibit cell growth to enhance the radiosensitivity of transplanted gastric tumor in vivo in nude mice.

Objective: To investigate the expression of cyclooxygenase-2(COX-2) and CEA in the tissues adjacent to the tumor within different distances., Methods: A total of 42 colorectal cancer tissues were collected.The adjacent tissues within 3 cm to the tumor were procured every 1 cm. Normal tissue was also collected. RNA was extracted and the expression of CEA and COX-2 was detected by RT-PCR., Results: The CEA mRNA levels of the tumor, the tissues of every 1 cm adjacent to the tumor, and the normal tissue were 135.2 ± 23.3, 78.2 ± 17.3, 75.9 ± 16.5, 56.2 ± 10.7, 52.3 ± 12.8, 18.2 ± 7.9, 16.2 ± 6.5, and 16.6 ± 7.0. The levels of COX-2 mRNA in above positions were 134.9 ± 31.1, 79.2 ± 20.2, 77.0 ± 20.5, 62.7 ± 21.9, 58.0 ± 18.1, 21.2 ± 10.3, 18.3 ± 7.6, and 17.1 ± 6.3. These data showed a decreasing trend of CEA and COX-2 as the distance increased from the tumor. The CEA mRNA levels showed positive correlation with the levels of COX-2 mRNA(r=0.725, P<0.01)., Conclusion: CEA and COX-2 may be considered to be used as biomarkers for the study of molecular resection margin of colorectal cancer.

Objective: To investigate the effect of phosphatidylinositol 3-kinase inhibitor LY294002 combined with NF-κB P65 nuclear translocation inhibitor SN50 on the tumor cell growth and apoptosis using a nude mouse model of gastric cancer., Methods: Human gastric cancer cell strain SGC7901 was transplanted subcutaneously to nude mice to establish tumor models. Model mice were randomly divided into the control group, the LY294002 treatment group, the SN50 treatment group, and the LY294002+SN50 treatment group, with 5 in each group. After being treated for 10 days, the inhibition rate of tumor growth was ascertained by measuring the size of tumor. Immunohistochemical method was used to detect the expression levels of Bcl-2, P53 and Bax proteins and transmission electron microscopy to investigate the apoptosis of tumor cells., Results: On the 10th day after treatment, the inhibition rate of gastric cancer cellular growth in the LY294002+SN50 group was (49.2±2.5)%, which was significantly higher than that in the LY294002 group(29.4±1.5)% and SN50 group (19.7±1.6)%(P<0.05). In comparison with the other two groups, LY294002+SN50 group exhibited more severe apoptosis, with expression of Bcl-2 decreased and that of P53 and Bax increased more significantly(P<0.05)., Conclusion: LY294002 combined with SN50 inhibits the growth of SGC7901 transplanted tumor and aggravates the apoptosis of gastric cancer cells in nude mice model.

Background/aims: To compare transanal endoscopic microsurgery (TEM) with conventional radical surgery (CRS) for T1 rectal cancer focusing on safety, feasibility and efficacy of both procedures., Methodology: An online search of Ovid, Medline, Embase, Pubmed and Cochrane Controlled Trials Register was undertaken to identify studies comparing TEM with CRS published in English between 1984 and March 2010. Only studies comparing TEM with CRS for T1 rectal cancer treatment and with a minimum of 20 cases were included. The parameters compared were postoperative complications, hospital mortality, recurrence rate and 5-year survival., Results: Five studies met screening criteria and 397 patients were enrolled in the meta-analysis; 216 were treated with TEM and the rest received CRS. Complications were observed in 16/196 in the TEM group and 77/163 in the CRS group. The difference was significant (p=0.01). The rate of mortality was 3.68% in CRS group, and 0 in TEM group (p=0.01). The 5-year survival was similar (p=0.84), the TEM group was 80.1% and the CRS group was 81.0%. However, there was more recurrence in the TEM group compared to CRS group (p=0.0004). TEM group was 12.0%, while CRS group was 0.5%., Conclusion: Compared with CRS, TEM had significant shorter hospital stay and fewer postoperative complications. TEM is a safe, feasible and effective option for T1 rectal cancer. Though TEM had a slightly higher rate of recurrence than CRS, no significant difference on 5-year survival was observed.

Aim: To investigate the anti-tumor effects of nuclear factor-κB (NF-κB) inhibitor SN50 and related mechanisms of SGC7901 human gastric carcinoma cells., Methods: MTT assay was used to determine the cytotoxic effects of SN50 in gastric cancer cell line SGC7901. Hoechst 33258 staining was used to detect apoptosis morphological changes after SN50 treatment. Activation of autophagy was monitored with monodansylcadaverine (MDC) staining after SN50 treatment. Immunofluorescence staining was used to detect the expression of light chain 3 (LC3). Mitochondrial membrane potential was measured using the fluorescent probe JC-1. Western blotting analysis were used to determine the expression of proteins involved in apoptosis and autophagy including p53, p53 upregulated modulator of apoptosis (PUMA), damage-regulated autophagy modulator (DRAM), LC3 and Beclin 1. We detected the effects of p53-mediated autophagy activation on the apoptosis of SGC7901 cells with the p53 inhibitor pifithrin-α., Results: The viability of SGC7901 cells was inhibited after SN50 treatment. Inductions in the expression of apoptotic protein p53 and PUMA as well as autophagic protein DRAM, LC3 and Beclin 1 were detected with Western blotting analysis. SN50-treated cells exhibited punctuate microtubule-associated protein 1 LC3 in immunoreactivity and MDC-labeled vesicles increased after treatment of SN50 by MDC staining. Collapse of mitochondrial membrane potential Δψ were detected for 6 to 24 h after SN50 treatment. SN50-induced increases in PUMA, DRAM, LC3 and Beclin 1 and cell death were blocked by the p53 specific inhibitor pifithrin-α., Conclusion: The anti-tumor activity of NF-κB inhibitors is associated with p53-mediated activation of autophagy.

Umbilical metastases from intraperitoneal malignancies are universally referred to Sister Mary Joseph's nodule (SMJN). The most frequent primary tumor sites include the stomach and ovaries. SMJN caused by colon cancer is uncommon. Likewise, carcinoma of the right side colon metastasizing to inguinal lymph nodes is considered almost impossible. To the best of our knowledge, there is no report of right side colon cancer synchronously involving both the umbilicus and inguinal lymph nodes in the literature. We present a case of right side colon cancer (RSCC) metastasizing to the umbilicus and inguinal lymph nodes, which was confirmed by routine pathological evaluation and immuohistochemistry.

Aim: To investigate the effects of class I phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 on the invasiveness and related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice., Methods: Nude mice were randomly divided into model control groups and LY294002 treatment groups. On days 5, 10 and 15 after treatment, the inhibitory rate of tumor growth, pathological changes in tumor specimens, expression levels of matrix metalloproteinase (MMP)-2, MMP-9, CD34 [representing microvessel density (MVD)] and vascular endothelial growth factor (VEGF), as well as apoptosis indexes in tumor samples were observed., Results: In this study, we showed that treating the tumors with LY294002 could significantly inhibit carcinoma growth by 11.3%, 29.4% and 36.7%, after 5, 10 and 15 d, respectively, compared to the control group. Hematoxylin & eosin staining indicated that the rate of inhibition increased progressively (23.51% +/- 3.11%, 43.20% +/- 3.27% and 63.28% +/- 2.10% at 5, 10 and 15 d, respectively) along with apoptosis. The expression of MMP-2 was also downregulated (from 71.4% +/- 1.6% to 47.9% +/- 0.7%, 31.9% +/- 0.9% and 7.9% +/- 0.7%). The same effects were observed in MMP-9 protein expression (from 49.4% +/- 1.5% to 36.9% +/- 0.4%, 23.5% +/- 0.9% and 7.7% +/- 0.6%), the mean MVD (from 51.2% +/- 3.1% to 41.9% +/- 1.5%, 30.9% +/- 1.7% and 14.9% +/- 0.8%), and the expression of VEGF (from 47.2% +/- 3.1% to 25.9% +/- 0.5%, 18.6% +/- 1.2% and 5.1% +/- 0.9%) by immunohistochemical staining., Conclusion: The class I PI3K inhibitor LY294002 could inhibit the invasiveness of gastric cancer cells by downregulating the expression of MMP-2, MMP-9, and VEGF, and reducing MVD.

Objective: To screen the radiosensitivity-related genes of colorectal cancer cells., Methods: Gene expression profiles of two different radiosensitivity cells(colorectal cancer cell line Lovo and SW480) were obtained by cDNA array and the differences of gene expression profiles between the two cells were analyzed., Results: Genes of more than 2-fold expressive differentiation were screened. In Lovo cells, 908 up-regulated genes were found, including higher expression genes CEACAM5, THBS1, SERPINE2, ARL7, HPGD, while 1312 genes were down-regulated. In SW480 cells, higher expression genes were SCD, NQ01, LYZ, KRT20 and ATP1B1., Conclusion: Gene profiles can reflect the radiosensitivity of colorectal cancer cells, which will provide the choice for the further study of radiosensitivity in colorectal cancer.

Aim: To study the effects of LY294002, an inhibitor of class I phosphatidylinositol 3-kinase (PI3K), on proliferation and apoptosis of SGC7901 gastric cancer cells., Methods: The MTT assay was used to determine the cytotoxic effects of LY294002. Cell cycle distribution was analyzed using flow cytometry and apoptosis was assessed using flow cytometry analysis after staining DNA with propidium iodide. Mitochondrial membrane potential was measured using the fluorescent probe JC-1. Expression of p53 and PUMA was determined using real-time RT-PCR and Western blotting analysis., Results: The viability of SGC7901 cells was significantly reduced by LY294002 treatment. Expression of p53 and PUMA was induced, and mitochondrial membrane potential collapsed after treatment with LY294002. LY294002 induced apoptotic cell death., Conclusion: Activation of the p53 pathway is involved in LY294002-induced SGC7901 cell death.

Background: Hypoxia-inducible factor-1alpha (HIF-1alpha), a subunit of hypoxia-inducible factor-1 (HIF-1), furnishes tumor cells with the means of adapting to stress parameters, such as tumor hypoxia, and promotes critical steps in tumor progression and aggressiveness by inducing angiogenesis and regulating energy metabolism. In this study, we investigated the relationship between HIF-1alpha and vascular endothelial growth factor (VEGF) and clinicopathologic characteristics, and evaluated the role of HIF-1alpha expression in patients with rectal adenocarcinoma., Patients and Methods: The immunohistochemical expression of HIF-1alpha and VEGF was evaluated in 30 formalin-fixed, paraffin-embedded postoperative rectal adenocarcinoma tissue samples. Correlations with clinicopathologic characteristics were determined by cross-tabulations. The impact of the immunoreactivity of HIF-1alpha with regard to the overall survival and local control endpoints was determined by univariate analyses., Results: Increased HIF-1alpha expression was strongly associated with VEGF positivity (P = 0.002), Dukes stage (P = 0.017), and lymph node metastasis (P = 0.001). No correlation was found between the level of HIF-1alpha expression and histologic grade (P = 0.63). The Kaplan-Meier curves showed a significantly shorter overall survival (P = 0.0087) and local control (P = 0.0438) for patients with high HIF-1alpha expression., Conclusion: These results show that HIF-1alpha might represent an important biologic marker evaluating the prognosis of patients with rectal adenocarcinoma.