Applications of gastric peroral endoscopic myotomy in the treatment of upper gastrointestinal tract disease

Gastric peroral endoscopic myotomy(G-POME)is an emerging minimally invasive endoscopic technique involving the establishment of a submucosal tun-nel around the pyloric sphincter.In 2013,Khashab et al used G-POME for the first time in the treatment of gastroparesis with enhanced therapeutic efficacy,prov-iding a new direction for the treatment of gastroparesis.With the recent and rapid development of G-POME therapy technology,progress has been made in the treatment of gastroparesis and other upper digestive tract diseases,such as congenital hypertrophic pyloric stenosis and gastric sleeve stricture,with G-POME.This article reviews the research progress and future prospects of G-POME for the treatment of upper digestive tract gastrointestinal diseases.

The receptor for β2GPⅠon membrane of hepatocellular carcinoma cell line SMMC-7721 is annexin Ⅱ

AIM: To evaluate the receptor protein which can specifically bind to β2GPⅠon the membrane of hepatocellular carcinoma (HCC) cell line SMMC-7721, and to study the biological function of the receptor.METHODS: Through β2GPⅠ-affinity chromatography column, the peptid-polysome-mRNA complex, which can specially bind to β2GPⅠ, stayed with the column and was separated from the whole polysome of liver cells, and then eluted and collected. Using cDNA synthesis kit and cDNA PCR kit, the corresponding cDNA was obtained and sequenced. RT-PCR was used to amplify annexinⅡ, and flow cytometry was used to study the competitive binding of annexinⅡ with β2GPⅠto SMMC-7721.RESULTS: A total of 1.1 kb of the cDNA fragment of the specific binding protein of β2GPⅠon liver cell membrane was obtained. The sequence of cDNA shared high homology with human annexinⅡ (98%). AnnexinⅡ was expressed on the membrane of SMMC-7721, and could compete with β2GPⅠfor combining with SMMC-7721.CONCLUSION: The receptor for β2GPⅠon membrane of SMMC-7721 cells is annexinⅡ, which might bridge HBV to infect hepatocytes.

Comprehensive treatment and a rare presentation of Cronkhite–Canada syndrome: Two case reports and review of literature

BACKGROUND Cronkhite–Canada syndrome(CCS)is a rare sporadic polyposis syndrome that presents with gastrointestinal and ectodermal symptoms in addition to nutritional deficiencies.CCS combined with hypothyroidism is an even rarer condition,with no standard treatment guidelines.CASE SUMMARY The present study described 2 patients with CCS:A 67-year-old woman with concomitant hypothyroidism and 68-year-old man treated with endoscopic mucosal resection(EMR).Both patients had multiple gastrointestinal symptoms and ectodermal changes,along with multiple gastrointestinal polyps.Microscopic examination showed that the mucosa in both patients was hyperemic and edematous,with pathologic examination showing distorted,atrophic,and dilated glands.Patient 1 had concomitant hypothyroidism and was treated with levothyroxine.Due to her self-reduction of hormone dose,her disease relapsed.Patient 2 underwent EMR,but refused further hormonal or biological treatments.Subsequently,he was treated with an oral Chinese medical preparation.CONCLUSION Pharmacotherapy can induce and maintain remission in CCS patients,with adjuvant EMR,long-term follow-up,and endoscopic surveillance being necessary.Case 1:Based on the aforementioned findings,Patient 1 was diagnosed with CCS and hypothyroidism.Case 2:Based on the aforementioned findings,Patient 2 was diagnosed with CCS.

Malignant solitary fibrous tumor of the greater omentum: A case report and review of literature

BACKGROUND Malignant solitary fibrous tumors(SFTs)account for 15%-20%of all SFTs,and malignant SFTs arising from the greater omentum are extremely rare.Most malignant SFTs of the greater omentum are diagnosed via pathological examinations after surgery.In this study,we report a case of malignant omental SFT and review the published literature on this rare malignancy.CASE SUMMARY A 64-year-old female presented with an abdominal mass,and underwent exploratory surgery,during which a huge tumor originating from the greater omentum and intraperitoneal implants were identified and resected.The results of the pathological examination,immunohistochemistry staining,and gene sequencing led to the diagnosis of malignant SFT of the greater omentum.The patient died one and a half years later due to tumor recurrence and metastasis.CONCLUSION This is the first report of the application of gene sequencing in the diagnosis of malignant SFTs of the greater omentum.

Knockdown of STAT3 by iRNA Inhibiting Migration and Invasion of Epithelial Ovarian Cancer Cells

Signal transducer and activator of transcription 3（STAT3） is a dual functional transcription factor with the functions of signal transduction and transcription regulation. It is reported that the expression of STAT3 in ovarian cancer is significantly higher and STAT3 can facilitate ovarian cancer growth and metastasis. To clarify the definite effect and molecular mechanism of STAT3 involved in ovarian cancer growth and metastasis, STAT3 expression was significantly downregulated by transfecting ovarian cancer model SK-OV-3 cells with the plasmid vector which express specific RNAi that targets human STAT3. The downregulated STAT3 not only decreased the invasion and migration but also inhibited the proliferation of SK-OV-3 cells. Western blot assay shows that the expression of vascular endothelial growth factor（VEGF） and that of Survivin were reduced in the cells with the plasma vector expressing specific RNAi that targets human STAT3. These results demonstrate that STAT3 involved in the invasion and migration of SK-OV-3 regulates the expression of VEGF and Survivin. In addition, VEGF and Survivin could play an important role in ovarian cancer growth and metastasis.

Inhibition of Dual Specific Oncolytic Adenovirus on Esophageal Cancer via Activation of Caspases by a Mitochondrial-dependent Pathway

We investigated the anti-tumor effects of dual cancer specific-oncolytic adenovirus Ad-VP on esophageal cancer（EC）. The anti-tumor activity of Ad-VP was compared with that of the control recombinant adenoviruses （Ad-GP, Ad-Apoptin, Ad-EGFP） in human esophageal cancer cell EC-109 and human normal liver cell L02 in vitro. In 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assays, the growth of EC-109 cells was slightly inhibited by Ad-GP, Ad-Apoptin and Ad-EGFE However, Ad-VP induced a significant cytotoxic effect. Infection of EC-109 cells with Ad-VP resulted in a significant induction of apoptosis of them in vitro, detected by 4＇,6-diamidino-2-phenylindole（DAPI） or acridine orange and ethidium bromide staining. The results of Western blot and flow cytometric assay indicate the loss of mitochondrial membrane potential（Aψm）, the release of eytochrome c and the activation of caspase-3, 6 and 7 in Ad-VP infected EC-109 cells. In contrast, all these assays show almost no effects of the recombinant adenoviruses on L02 cells. These results demonstrate that the treatment of tumors with Ad-VP selectively inhibits tumor growth and induces apoptosis of esophageal cancer cells. Ad-VP may provide a novel and powerful strategy for cancer gene therapy.

Silencing of signal transducer and activator of transcription 3 expression by RNA interference suppresses growth of human hepatocellular carcinoma in tumor-bearing nude mice

AIM:To explore the effect of silencing of signal transducer and activator of transcription 3(STAT3) expression by RNA interference(RNAi) on growth of human hepatocellular carcinoma(HCC) in tumor-bearing nude mice in vivo.METHODS:To construct the recombinant plasmid of pSilencer 3.0-H1-STAT3-siRNA-GFP(pSH1-siRNA-STAT3) and establish the tumor-bearing nude mouse model of the HCC cell line SMMC7721,we used intratumoral injection together with electroblotting to transfect the recombinant plasmid pSH1-siRNA-STAT3 into the transplanted tumor.The weight of the nude mice and tumor volumes were recorded.STAT3 gene transcription was detected by semi-quantitative reverse transcription polymerase chain reaction(RTPCR).Level of protein expression and location of STAT3 were determined by Western blotting and immunohistochemical staining.STAT3-related genes such as survivin,c-myc,VEGF,p53 and caspase3 mRNA and protein expression were detected in tumor tissues at the same time.The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay was used to detect apoptosis of tumor cells.RESULTS:The weight of the treated nude mice increased,and the tumor volume decreased markedly compared with those of the mock-treated and negative control groups(P < 0.01).The results of RT-PCR and Western blotting showed that mRNA and protein levels of STAT3 declined markedly in the treated group.The change in STAT3-related gene expression in tumor tissues at the mRNA and protein level also varied,the expression of survivin,VEGF and c-myc were obviously reduced,and expression of p53 and caspase3 increased(P < 0.01).Most of the tumor tissue cells in the treated group developed apoptosis that was detected by TUNEL assay.CONCLUSION:Silencing of STAT3 expression by RNAi significantly inhibits expression of STAT3 mRNA and protein,and suppresses growth of human HCC in tumor-bearing nude mice.The mechanism may be related to down-regulation of survivin,VEGF and c-myc and up-regulation of p53 and caspase3 expression.Accordingly,the STAT3 gene may act as an important and effective target in gene therapy of HCC.

Anti-tumor Effects of a Recombinant Fowlpox Virus Expressing Apoptin on Human Cervical Carcinoma in Vivo and in Vitro

Apoptin is a chicken anemia virus-derived,p53-independent,bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis of various human tumor cells,but not of normal diploid cells.To explore the application of apoptin in tumor gene therapy,we used a recombinant fowlpox virus expressing apoptin protein （vFV-Apoptin） to investigate the anti-tumor effectes of vFV-Apoptin on human cervical carcinoma（HeLa） cells in vivo and in vitro through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide（MTT） assay,acridine orage/ethidium bromide（AO/EB） and annexin V staining test,respectively.The results show that vFV-Apoptin inhibites the proliferation of HeLa cells in vitro through inducing the apoptosis of HeLa cells,and the inhibition effect of vFV-Apoptin has a dose-effect and time-effect relationship.The results of animal models show that vFV-Apoptin significantly inhibits tumor growth,extends the lifespan of animals and improves the mean survival.Experimental results indicate that vFV-Apoptin has a potential application in the tumor gene therapy.

Anticancer Effects of Fusion Protein CAtin on DMBA-induced Carcinogenesis in Buccal Pouch of Chinese Hamster

Aberrant expression of carcinoembryonic antigen（CEA） is a common feature for multiple types of cancer,which makes it an attractive target for anticancer therapy.CAtin is a novel dual cancer-specific fusion protein,composed of an anti-CEA single-chain disulfide-stabilized Fv antibody（scdsFv） and Apoptin,a tumor-specific apoptosis-inducing protein.Oral squamous cell carcinoma（OSCC） is an important healthcare problem in the clinic.To evaluate the anticancer effects of CAtin on OSCC,7,12-dimethylbenz[a]anthracene（DMBA） was used to induce oral carcinogenesis and premalignant lesions in the buccal pouch of Chinese hamster,and the antitumor effects of CAtin were determined in pre-cancer,cancer and post-operatative cancer models,respectively.The results show that the administration of CAtin delayed the malignant transformation of early stage cancerous lesions,inhibited the growth of established solid oral tumors and reduced the post-operatative relapse of lesions,with no significant systemic toxicity.This study demonstrates that CAtin may have potential for the treatment of OSCC,and the development of preventive strategies based on CAtin may offer a practical approach for the treatment of human oral tumors.

Induction of Effective Antitumor Immune Response by Combined Administration of hIL-18 and NDV HN

To analyze the antitumor potential and mechanism of action of simultaneous Newcastle disease virus （NDV） hemagglutinin-neuraminidase（HN） and human interleukin 18（hIL-18） gene transfer in C57BL/6 mice with H22 hepatoma,the mouse model with H22 hepatoma was established in C57BL/6 mice, and the antitumor effects of the combined application of NDV HN and hIL-18 were evaluated in vivo. The results show that the growth of established tumors in mice immunized with adenovirus（Ad）-HN in conjunction with Ad-hIL-18 was significantly inhibited compared with that in mice immunized with Ad-HN, Ad-hIL-18 alone, or the empty vector（Ad-mock）. Furthermore, the immunization of mice with Ad-HN in conjunction with Ad-hIL-18 elicited strong natural killer activity and H22 tumor-specific cytotoxic T lymphocyte（CTL） responses in vivo. In addition, T cells from the lymph nodes of mice immunized with Ad-hIL-18 or Ad-HN＋Ad-hIL-18 secreted high levels of the Th1 cytokine IL-2 and interferon-γ （IFN-γ）, indicating that the regression of tumor cells is related to a Th1-type dominant immune response. These results demonstrate that vaccination with NDV HN together with hIL-18 may be a novel and powerful strategy for cancer immunotherapy.

A Novel Schiff Base Zinc Coordination Compound Inhibits Proliferation and Induces Apoptosis of Human Osteosarcoma Cells

Various kinds of schiff base metal complexes have been proven to induce apoptosis of tumor cells. However,it remains largely unknown whether schiff base zinc complexes induce apoptosis in human cancer cells. Here,we synthesized a novel schiff base zinc coordination compound（SBZCC） and investigated its effects on the growth,proliferation and apoptosis of human osteosarcoma MG-63 cells. A novel SBZCC was synthesized by chemical processes and used to treat MG-63 cells. The cell viability was determined by CCK-8 assay. The cell cycle progression,mitochondrial membrane potential and apoptotic cells were analyzed by flow cytometry. The apoptosis-related proteins levels were determined by immunoblotting. Treatment of MG-63 cells with SBZCC resulted in inhibition of cell proliferation and cell cycle arrest at G1 phase. Moreover,SBZCC significantly reduced the mitochondrial membrane potential and induced apoptosis,accompanied with increased Bax/Bcl-2 and Flas L/Fas expression as well as caspase-3/8/9 cleavage. Our results demonstrated that the synthesized novel SBZCC could inhibit the proliferation and induce apoptosis of MG-63 cells via activating both the mitochondrial and cell death receptor apoptosis pathways,suggesting that SBZCC is a promising agent for the development as anticancer drugs.

Photoswitchable semiconducting polymer dots with photosensitizer molecule and photochromic molecule loading for photodynamic cancer therapy

Photodynamic therapy(PDT)is a new and rapidly developing treatment modality for dinical cancer therapy.Semiconductor polymer dots(Pdots)doped with photosensitizers have been successfully applied to PDT,and have made progress in the field of tumor therapy.However,the problems of severe photosensitivity and limited tisue penetration depth are needed to be solved during the implementation process of PDT.Here we developed the Pdots doped with photosensitizer molecule Chlorin e6(Ce6)and photochromic molecule 1,2-bis(2,4-dimethy1-5 phenyl-3-thiophene)-3,3,4,5-hexafuoro-1-cyclopentene(BTE)to construct a photoswitchable nanoplatform for PDT.The Ce6-BTE-doped Pdots were in the green region,and the tissue penetration depth was increased compared with most Pdots in the blue region.The reversible conversion of BTE under different light irradiation was utilized to regulate the photodynamic effect and solve the problem of photosensitivity.The prepared Ce6-BTE-doped Pdots had small size,excellent optical property,efficient ROS generation and good photoswitchable ability.The cellular uptake,cytotoxicity,and photodynamic effect of the Pdots were detected in human colon tumor cells.The experiments in vitro indicated that Ce6-BTE-doped Pdots could exert excellent photodynamic effect in ON state and reduce photosensitivity in OFF state.These results demonstrated that this nanoplatform holds the potential to be used in clinical PDT.

Ubiquitin-like modifier activating enzyme 2 promotes cell migration and invasion through Wnt/β-catenin signaling in gastric cancer

AIM To investigate the function and mechanism of ubiquitinlike modifier activating enzyme 2(Uba2) in progression of gastric cancer(GC) cells.METHODS Uba2 level in patients with GC was analyzed by Western blotting and immunohistochemistry. MTT and colony formation assays were performed to examine cell proliferation.Flow cytometry was used for cell cycle analysis.Wound healing and Transwell assays were conducted to examine the effects of Uba2 on migration and invasion.Expression levels of cell cycle-related proteins, epithelial-mesenchymal transition(EMT) biomarkers, and involvement of the Wnt/β-catenin pathway was assessed by Western blotting. Activation of the Wnt/β-catenin pathway was confirmed by luciferase assay.RESULTS Uba2 expression was higher in GC than in normal tissues.Increased Uba2 expression was correlated with tissue differentiation, Lauren's classification, vascular invasion,and TNM stage, as determined by the analysis of 100 GC cases(P < 0.05). Knock-down of Uba2 inhibited GC cell proliferation, induced cell cycle arrest, and altered expression of cyclin D1, P21, P27, and Bcl-2, while upregulation of Uba2 showed the opposite effects. The wound healing and Transwell assays showed that Uba2 promoted GC cell migration and invasion. Western blotting revealed alterations in EMT biomarkers, suggesting the role of Uba2 in EMT. Furthermore, the luciferase reporter assay indicated the involvement of the Wnt/β-catenin signaling pathway as a possible modulator of Uba2 oncogenic functions.CONCLUSION Uba2 plays a vital role in GC cell migration and invasion,possibly by regulating the Wnt/β-catenin signaling pathway and EMT.

Antitumor Effects of Newcastle Disease Virus Hemagglutinin-neuraminidase Used as a Molecular Adjuvant

Gene therapy is a potentially powerful tool used in cancer therapy. The strength of immune responses in- duced by some strategies is usually low, therefore, the development of agents capable of enhancing these responses is highlighted. The authors investigated the potential of an approach based on the hemagglutinin-neuraminidase（HN） of Newcastle disease virus（NDV） as a potential immune adjuvant. It was found that recombinant adenovirus（Ad） in- fected SGC7901 cells expressing HN exhibited both hemagglutinin（HA） and neuraminidase（NA） activities. It was demonstrated that administration of HN induced higher levels of the effector cytokines TNF-a, IFN-a and IFN-y and increased natural killer（NK） cell activity. Based on the therapeutic tumor model, the results show that the administra- tion of HN with Apoptin led to improved survival and tumor suppression. In conclusion, this study indicates that HN stimulates innate immune responses to make the activity of NK cells increased, which highlights the potential adju- vant activity of HN in cancer gene therapy.

Semiconducting polymer dots with photosensitizer loading and peptide modification for enhanced cell penetration and photodynamic effect

This letter describes semiconducting polymer dots （Pdots） doped with a photosensitizer and modified with a cell penetrating peptide for photodynamic therapy （PDT）. The resulting Pdots exhibited efficient singlet oxygen （^1O2） generation mediated by intraparticle energy transfer. Experimental results indicated that the peptide-coated Pdots could promote the cellular uptake and increase the penetration efficiency in vitro, and effectively suppressed tumor growth and enhanced the photodynamic effect in vivo. Our results demonstrate that Pdots with photosensitizer loading and peptide modification hold great promise for cancer therapy.