Absent in melanoma 2 attenuates proliferation and migration and promotes apoptosis of human colorectal cancer cells by activating P38MAPK signaling pathway.

Colorectal cancer (CRC) stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally. Absent in melanoma 2 (AIM2), a constituent of the interferon-inducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family, contributes to both cancer progression and inflammasome activation. Despite this understanding, the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive. Consequently, this study endeavors to assess AIM2's expression levels, explore its potential antitumor effects, elucidate associated cancer-related processes, and decipher the underlying signaling pathways in CRC. Our findings showed a reduced AIM2 expression in most CRC cell lines. Elevation of AIM2 levels suppressed CRC cell proliferation and migration, altered cell cycle by inhibiting G1/S transition, and induced cell apoptosis. Further research uncovered the participation of P38 mitogen-activated protein kinase (P38MAPK) in AIM2-mediated modulation of CRC cell apoptosis and proliferation. Altogether, our achievements distinctly underscored AIM2's antitumor role in CRC. AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway, indicating AIM2 as a prospective and novel therapeutic target for CRC.

Mendelian randomization study of causal link from gut microbiota to colorectal cancer.

Recent studies have shown the relevance of gut microbiota in the occurrence and development of colorectal cancer (CRC), but the causal relationship remains unclear in the human population. The present study aims to assess the causal relationship from the gut microbiota to CRC and to identify specific causal microbe taxa via genome-wide association study (GWAS) summary statistics based two-sample Mendelian randomization (MR) analyses. Microbiome GWAS (MGWAS) in the TwinsUK 1,126 twin pairs was used as discovery exposure sample, and MGWAS in 1,812 northern German participants was used as replication exposure sample. GWAS of CRC in 387,156 participants from the UK Biobank (UKB) was used as the outcome sample. Bacteria were grouped into taxa features at both family and genus levels. In the discovery sample, a total of 30 bacteria features including 15 families and 15 genera were analyzed. Five features, including 2 families (Verrucomicrobiaceae and Enterobacteriaceae) and 3 genera (Akkermansia, Blautia, and Ruminococcus), were nominally significant. In the replication sample, the genus Blautia (discovery beta=-0.01, P = 0.04) was successfully replicated (replication beta=-0.18, P = 0.01) with consistent effect direction. Our findings identified genus Blautia that was causally associated with CRC, thus offering novel insights into the microbiota-mediated CRC development mechanism.

Retraction Note to: Lupeol induces apoptosis and inhibits invasion in gallbladder carcinoma GBC-SD cells by suppression of EGFR/MMP-9 signaling pathway.

[This retracts the article DOI: 10.1007/s10616-014-9763-7.].

[Retracted] Aberrant expression of B7­H3 in gastric adenocarcinoma promotes cancer cell metastasis.

Following the publication of the above paper, an interested reader drew to the authors' attention that the scratch­wound assay data featured in Fig. 5A on p. 2090 appeared to contain some overlapping data comparing between the panels, such that these data, which were intended to show the results from differently performed experiments, may have been derived from the same original source. After having re­examined their original data, the authors conceded that the figure had been assembled incorrectly (specifically, four of the images selected out of the nine data panels included in this figure part had been chosen erroneously). Furthermore, the first author on the paper (Wei Dai) also acknowledged that several of the named authors had not given their prior consent to be included as such as authors on the paper, and therefore a request was made that the paper be retracted from the publication. In view of these admissions, the Editor of Oncology Reports has accepted the authors' request that the paper be retracted from the journal. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 32: 2086­2092, 2014; DOI: 10.3892/or.2014.3405].

The Feasibility and Potential Advantages of Laparoscopic Management of Incarcerated Obturator Hernia Over the Open Approach.

PURPOSE: The purpose of this study was to explore the feasibility and potential advantages of laparoscopic surgery in the treatment of incarcerated obturator hernia (IOH). MATERIALS AND METHODS: Clinical data of 23 patients with IOH who underwent emergency surgery at our hospital from June 2015 to October 2020 were retrospectively analyzed. The clinical characteristics and surgery outcomes were compared between the laparoscopic group, open group, and the previously published data. RESULTS: Twelve patients with IOH were treated by laparoscopic management, while 11 patients with IOH underwent open surgery. There was no statistically significant difference in preoperative general data between the 2 groups, while the laparoscopic group had less intraoperative blood loss, shorter postoperative hospital stay, and lower postoperative complications compared with open group. Furthermore, when compared with the open group reported in previous literature, which showed similar conclusions. CONCLUSION: Laparoscopic surgery for IOH showed more favorable advantages including less intraoperative blood loss, shorter postoperative hospital stay, and lower postoperative complications compared with an open approach, which is a safe and feasible minimally invasive strategy and has certain advantages.

Retraction: Oxymatrine Synergistically Potentiates the Antitumor Effects of Cisplatin in Human Gastric Cancer Cells.

[This retracts the article DOI: 10.7150/jca.28532.].

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer.

Gallbladder cancer is one of the most common malignant tumors in the biliary tract. In recent years, the chemotherapy treatment for gallbladder carcinoma has exhibited obvious characteristics of drug resistance and insensitivity, and one of the main factors is the existence of cancer stem cells. Here in this study, the effect of Bufalin on gallbladder cancer (GBC-SD) cells and the related mechanism were studied. The results indicated that Bufalin could inhibit the growth of gallbladder carcinoma both in vivo and in vitro. According to the biological behavior analysis, Bufalin induced apoptosis, inhibited the propagation, migration and invasion of GBC-SD cells, and blocked cell cycle at the G2/M stage. Besides, Bufalin inhibited the tumor sphere formation capability of gallbladder carcinoma in matrigel, reduced the expression of multiple stemness-associated proteins, including Oct4, Sox2 and the stem cell-surface marker proteins CD133 and CD44. Western blot assay showed that Bufalin inhibited MEK/ERK and PI3-K/AKT signaling pathways by inhibiting the expression of p-c-Met, which in turn affected the expression of apoptosis-related protein Mcl-1, and the invasion-associated proteins E-cadherin, MMP9 and Snail. Bufalin was found to have an inhibitory effect on the GBC-SD cell growth and reduce the self-renewal and characteristic of gallbladder cancer stem cells. It enhanced the chemotherapeutic sensitivity and reduced the metastasis of gallbladder carcinoma. In conclusion, Bufalin can be used as a new promising anticancer drug for gallbladder cancer patients who are resistant to traditional chemotherapy.

Laparoscopic diagnosis and extraction of an ingested fish bone that penetrated the stomach: A case report.

RATIONALE: Foreign body ingestion is a common clinical event, but serious complication such as perforation is uncommon. Here we present a case of gastrointestinal perforation caused by fish bone, which was treated effectively and successfully by totally laparoscopic management. PATIENT CONCERNS: A 63-year-old man who was admitted to our hospital with epigastric pain for 1 month. Computed tomography of the abdomen at the local hospital revealed a linear, hyperdense, foreign body in the lesser curvature of gastric antrum that had penetrated through the posterior wall of the gastric antrum. DIAGNOSIS: The laparoscopic exploration found that a 2.5 cm × 0.3 cm fish bone had penetrated through the posterior wall of the gastric antrum. INTERVENTIONS: A totally laparoscopic surgery was performed to remove the foreign body and repair the perforation eventually. OUTCOMES: After surgery, the patient underwent uneventful recovery and was discharged on postoperative day 7. During the 3 months of follow-up visit, the patient appeared healthy and did not report abdominal symptoms. LESSONS: In this case, the advantages of laparoscopic techniques in the diagnosis and treatment of gastrointestinal perforation caused by foreign body was confirmed, and which may be considered as the primary choice in similar cases.

S-Adenosylmethionine synergistically enhances the antitumor effect of gemcitabine against pancreatic cancer through JAK2/STAT3 pathway.

Gemcitabine (GEM) has been widely used for pancreatic cancer (PC) treatment but limited by the development of drug resistance. The agents that reverse its resistance and improve the chemo-sensitivity are urgently needed. S-Adenosylmethionine (SAM) is a precursor for polyamine biosynthesis in mammalian cells and plays a key role in biological transmethylation events. It is reported that SAM could be used as a therapeutic reagent for cancer treatments. In this study, we investigated the chemo-sensitization of SAM to potentiate the antitumor effect of GEM in PC. After treating PC cells with GEM and/or SAM, different subsequent experiments were performed. Results showed that SAM plus GEM could significantly inhibit the growth and proliferation of PC cells, and SAM acts synergistically with GEM. The combinative treatment could induce cell apoptosis and inhibit invasion and migration through JAK2/STAT3 inactivation. Inhibition of JAK2/STAT3 pathway significantly enhanced the pro-apoptotic effect of SAM, suggesting the key roles of JAK2/STAT3 in the process. Moreover, co-treatment with GEM and SAM exhibited more efficient inhibition of tumor weight and volume on PANC-1 xenograft mouse model compared to GEM or SAM alone and has no significant effect on the function of the liver and kidney. In general, this study indicated that SAM synergistically enhanced the antitumor effect of GEM against PC through suppressed JAK2/STAT3 pathway, and SAM is applicable as a promising agent to improve the sensitivity of PC to GEM.

Comparative study of outcomes of Roux-en-Y reconstruction and Billroth â reconstruction performed after radical distal gastrectomy.

BACKGROUND: Billroth Ⅰ (BⅠ) reconstruction and Roux-en-Y (RY) reconstruction are both commonly performed after distal gastrectomy (DG). We conducted a retrospective study to evaluate which is the better option. METHODS: Included in our study were 162 patients who, between April 2011 and October 2015, underwent DG followed by BⅠ reconstruction (n = 93) or RY reconstruction (n = 69). All patients were followed up for at least 1 year. We compared perioperative outcomes, postoperative complications, gastrointestinal (GI) symptoms, endoscopic findings, and nutritional status between the 2 groups of patients. RESULTS: Patient characteristics did not differ between the 2 groups, with the exception of the incidence of gastric body tumors, which was significantly higher in the RY group (73.9% vs. 19.4%; p < 0.001). Operation time was significantly longer in the RY reconstruction group (p < 0.001). There was no significant between-group difference in the grades of GI dysfunction (p = 0.122).The endoscopically determined RGB (Residual food, Gastritis, Bile reflux)scores were significantly better in the RY reconstruction group than in the BI reconstruction group (p = 0.027, p < 0.001,p < 0.001,respectively).There was also no significant between-group difference in the change (1-year postoperative value/preoperative value) in body weight, body mass index, serum albumin concentration, or total cholesterol concentration (p = 0.484,p = 0.613,p = 0.760,p = 0.890, respectively). CONCLUSIONS: RY reconstruction appears not to be advantageous over BⅠ reconstruction in terms of GI function or nutritional status 1 year after surgery. RY reconstruction does appear to be superior in terms of preventing bile reflux but takes more operation time.

TIGAR knockdown enhanced the anticancer effect of aescin via regulating autophagy and apoptosis in colorectal cancer cells.

Our previous study showed that TP53-induced glycolysis and apoptosis regulator (TIGAR) regulated ROS, autophagy, and apoptosis in response to hypoxia and chemotherapeutic drugs. Aescin, a triterpene saponin, exerts anticancer effects and increases ROS levels. The ROS is a key upstream signaling to activate autophagy. Whether there is a crosstalk between TIGAR and aescin in regulating ROS, autophagy, and apoptosis is unknown. In this study, we found that aescin inhibited cell viability and colony formation, and induced DNA damage, cell cycle arrest, and apoptosis in cancer cell lines HCT-116 and HCT-8 cells. Concurrently, aescin increased the expression of TIGAR, ROS levels, and autophagy activation. Knockdown of TIGAR enhanced the anticancer effects of aescin in vitro and in vivo, whereas overexpression of TIGAR or replenishing TIGAR downstream products, NADPH and ribose, attenuated aescin-induced apoptosis. Furthermore, aescin-induced ROS elevation and autophagy activation were further strengthened by TIGAR knockdown in HCT-116 cells. However, autophagy inhibition by knockdown of autophagy-related gene ATG5 or 3-methyladenine (3-MA) exaggerated aescin-induced apoptosis when TIGAR was knocked down. In conclusion, TIGAR plays a dual role in determining cancer cell fate via inhibiting both apoptosis and autophagy in response to aescin, which indicated that inhibition of TIGAR and/or autophagy may be a junctional therapeutic target in treatment of cancers with aescin.

Oxymatrine Synergistically Potentiates the Antitumor Effects of Cisplatin in Human Gastric Cancer Cells.

Cisplatin (CDDP) has been extensively used for gastric cancer (GC) treatment but limited by drug resistance and severe toxicity. The chemo-sensitizers that enhance its efficiency and overcome its limitation are urgently needed. Oxymatrine (OMT), a primary active ingredient from the dry roots of Sophora favescens, has shown powerful anti-cancer property with little side-effect. In this study, we explored the chemo-sensitization of OMT to potentiate the anti-tumor effect of CDDP. GC cell lines were dealt with OMT and/or CDDP and then subjected to different experimental methods. We found that OMT could significantly potentiate the CDDP-caused BGC-823 and SGC7901 cells viability loss, and OMT acts synergistically with CDDP. The combinative treatment could arrest cell cycle in G0/G1 phase by increasing p21, p27 and decreasing cyclin D1, and induced apoptosis by ROS generation and AKT/ERK inactivation. Inhibition of ROS respectively reversed the cell death induced by OMT and/or CDDP, suggesting the pivotal roles of ROS in the process. Moreover, OMT enhanced the antitumor effects of CDDP in nude mice bearing BGC823 tumor xenografts in vivo. Taken together, this study highlights that the co-treatment with OMT and CDDP exerted synergistic antitumor effects in GC cells, and that these effects may be mediated by ROS generation and inactivation of the AKT/ERK pathways.

Oct4 promotes cancer cell proliferation and migration and leads to poor prognosis associated with the survivin/STAT3 pathway in hepatocellular carcinoma.

Octamer­binding transcription factor 4 (Oct4) has been identified as a novel transcription factor associated with tumorigenesis, acquisition and maintenance of cancer stem cell characteristics and poor prognosis in tumors. However, the role of Oct4 in tumorigenesis and progression of hepatocellular carcinoma (HCC) has not yet been fully elucidated. In our present study, we observed that the Oct4 expression level was upregulated in HCC specimens as well as in different HCC cell lines. In in vitro experiments, decreased expression of Oct4 by shRNA inhibited the viability and mobility of HCC cells. Furthermore, the loss of Oct4 inhibited HCC cell malignant progression accompanied by downregulated expression of the survivin/signal transducer and activator of transcription 3 (STAT3) pathway. Liver cancer patients with high expression of Oct4 exhibited significantly shorter overall and disease­free survival. These findings demonstrated that Oct4 plays a vital role in the malignant progression of HCC cells through the survivin/STAT3 signaling pathway, and it may prove to be a novel biomarker associated with patient prognosis and survival.

Aescin-induced reactive oxygen species play a pro-survival role in human cancer cells via ATM/AMPK/ULK1-mediated autophagy.

Aescin, a natural mixture of triterpene saponins, has been reported to exert anticancer effect. Recent studies show that aescin increases intracellular reactive oxygen species (ROS) levels. However, whether the increased ROS play a role in the anticancer action of aescin remains to be explored. In this study, we demonstrated that aescin (20-80 µg/mL) dose-dependently induced apoptosis and activated mammalian target of rapamycin (mTOR)-independent autophagy in human hepatocellular carcinoma HepG2 cells and colon carcinoma HCT 116 cells. The activation of autophagy favored cancer cell survival in response to aescin, as suppression of autophagy with ATG5 siRNAs or 3-methyladenine (3-MA), a selective inhibitor of autophagy, promoted aescin-induced apoptosis in vitro, and significantly enhanced the anticancer effect of aescin in vivo. Meanwhile, aescin dose-dependently elevated intracellular ROS levels and activated Ataxia-telangiectasia mutated kinase/AMP-activated protein kinase/UNC-51-like kinase-1 (ATM/AMPK/ULK1) pathway. The ROS and ATM/AMPK/ULK1 pathway were upstream modulators of the aescin-induced autophagy, as N-acetyl-L-cysteine (NAC) or ATM kinase inhibitor (KU-55933) remarkably suppressed aescin-induced autophagy and consequently promoted aescin-induced apoptosis, whereas overexpression of ATG5 partly attenuated NAC-induced enhancement in aescin-induced apoptosis. In conclusion, this study provides new insights into the roles of aescin-mediated oxidative stress and autophagy in cancer cell survival. Our results suggest that combined administration of the antioxidants or autophagic inhibitors with aescin might be a potential strategy to enhance the anticancer effect of aescin.

Rottlerin upregulates DDX3 expression in hepatocellular carcinoma.

Rottlerin has been reported to exert its anti-tumor activity in various types of human cancers. However, the underlying molecular mechanism has not been fully elucidated. In the current study, we explored whether rottlerin exhibits its tumor suppressive function in hepatocellular carcinoma cells. Our MTT assay results showed that rottlerin inhibited cell growth in hepatocellular carcinoma cells. Moreover, we found that rottlerin induced cell apoptosis and caused cell cycle arrest at G1 phase. Furthermore, our wound healing assay result demonstrated that rottlerin retarded cell migration in hepatocellular carcinoma cells. Additionally, rottlerin suppressed cell migration and invasion. Notably, we found that rottlerin upregulated DDX3 expression and subsequently downregulated Cyclin D1 expression and increased p21 level. Importantly, down-regulation of DDX3 abrogated the rottlerin-mediated tumor suppressive function, whereas overexpression of DDX3 promoted the anti-tumor activity of rottlerin. Our study suggests that rottlerin exhibits its anti-cancer activity partly due to upregulation of DDX3 in hepatocellular carcinoma cells.

Oxymatrine induces apoptosis and inhibits invasion in Gallbladder carcinoma via PTEN/PI3K/AKT pathway.

Oxymatrine extracted from Sophora flavescens Ait as a natural polyphenolic phytochemical has been demonstrated to exhibit anti-tumor effects on various cancers, including Gallbladder carcinoma (GBC). However, its underlying mechanisms of function are largely unknown in GBC cells. The present study is conducted to investigate the anti-tumor effects and the underlying mechanisms of oxymatrine on GBC cells in vitro and in vivo. The results showed that oxymatrine inhibited cell viability, metastatic ability and induced cell apoptosis in dose-dependent manners. Furthermore, we found that the expression of p-AKT, MMP-2, MMP-9 and the ratio of Bcl-2/Bax were significantly down-regulated, while the expression of PTEN was up-regulated in GBC cells. In addition, pretreatment with a specific PI3K/AKT activator (IGF-1) significantly antagonized the oxymatrine-mediated inhibition of GBC-SD cells. Subsequently, our in vivo studies showed that administration of oxymatrine induced a significant dose-dependent decrease in tumor growth. In conclusion, these findings indicated that the inhibition of cells proliferation, migration, invasion and the induction of apoptosis in response to oxymatrine in GBC cells, may function through the suppression of PTEN/PI3K/AKT pathway, which was considered as the vital signaling pathway in regulating tumorigenesis. These results suggested that oxymatrine might be a novel effective candidate as chemotherapeutic agent against GBC.

Downregulation of MACC1 inhibits the viability, invasion and migration and induces apoptosis in esophageal carcinoma cells through the phosphatase and tensin homolog/phosphoinositide 3-kinase/protein kinase B signaling pathway.

As an oncogene, MACC1 serves an important function in cancer progression and metastasis. However, the effect of MACC1 in esophageal carcinoma (EC) remains to be fully understood. The present study assessed the association between MACC1 expression and the progression of EC cells. A small interfering (si)RNA was delivered into EC cells to downregulate MACC1 expression. The MTT assay demonstrated that EC cell viability was reduced by siRNA-MACC1. Decreasing MACC1 expression increased the apoptotic rate of EC cells compared with control cells. Transwell and Matrigel assays demonstrated that EC cell migration and invasion, respectively, were downregulated by siRNA-MACC1. Furthermore, knocking down MACC1 suppressed the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway by upregulating the expression of phosphatase and tensin homolog (PTEN), a tumor suppressor. The results of the present study revealed that MACC1 expression affected cellular functions of the EC cells through the PTEN/PI3K/Akt signaling pathway. Therefore, MACC1 may potentially serve as a novel biomarker and therapeutic target for EC.