Endoscopic resection techniques for colorectal neoplasia:Current developments

Endoscopic polypectomy and endoscopic mucosal resection(EMR) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as on shortening procedure times. Cold snare resection is the emerging standard for the treatment of smaller(< 5 mm) polyps and is possibly also suitable for the removal of noncancerous polyps up to 9 mm. The method avoids thermal damage, has reduced procedure times and probably also a lower risk for delayed bleeding. On the other end of the treatment spectrum, endoscopic submucosal dissection(ESD)offers en bloc resection of larger flat or sessile lesions. The technique has obvious advantages in the treatment of high-grade dysplasia and early cancer. Due to its minimal recurrence rate, it may also be an alternative to fractionated EMR of larger flat or sessile lesions. However, ESD is technically demanding and burdened by longer procedure times and higher costs. It should therefore be restricted to lesions suspicious for high-grade dysplasia or early invasive cancer.The latest addition to endoscopic resection techniques is endoscopic fullthickness resection with specifically developed devices for flexible endoscopy.This method is very useful for the treatment of smaller difficult-to-resect lesions,e.g., recurrence with scar formation after previous endoscopic resections.

Eradication of H pylori for the prevention of gastric cancer

有 H pylori 的感染是与胃的癌症联系的最重要的已知的病因学的因素。当有 H pylori 的胃粘膜的殖民导致活跃、长期的胃炎在时几乎，所有个人感染了，得胃的癌症的可能性取决于环境、细菌的毒力和主人 specific 因素。所有胃的癌症盒子的多数对 H pylori 感染并且因此可归因理论上可防止。从在一个早时间点的 H pylori 的根除能阻止的动物模型有证据胃的癌症开发。然而，使随机化在人在胃的癌症的发生上探索 H pylori 根除的预防效果的临床的审判仍然保持稀少并且让步了冲突结果。为在为 H pylori 的风险的病人的鉴定的更好的标记导致了胃的恶意被需要允许更有效的公共根除策略的发展。同时，屏蔽并且在胃的癌症病人以及某些高风险的人口的一度的亲戚的 H pylori 的治疗可能是有益的。

Orthotopic liver transplantation for giant liver haemangioma: A case report

In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease(lab MELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the lab MELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low lab MELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours.

L1 is a potential marker for poorly-differentiated pancreatic neuroendocrine carcinoma

瞄准：在胰腺的神经内分泌肿瘤决定 L1 的表示并且相关它与这个肿瘤的分类。方法：我们回顾地在原发性瘤或转移的石蜡节上由免疫组织化学在胰腺的神经内分泌肿瘤的 63 种情况中分析了 L1 表示。染色被过氧化物酶技术对人的 L1 与单音的同种细胞的抗体 UJ127.11 执行。所有肿瘤被分类根据分类同样区分得好的神经内分泌肿瘤和癌或糟糕区分的神经内分泌癌。结果：L1 在 5 被检测(7.9%) 63 个胰腺的神经内分泌肿瘤。(44.4%) 四 9 糟糕区分的癌表示了 L1。相反，仅仅(1.9%) 1 为 L1 54 个区分得好的肿瘤或癌是积极的。没有表示在正常胰腺的织物的 Langerhans 小岛房间被发现。生气桌子分析显示出在 L1 表示和胰(P【0.01 ) 的神经内分泌肿瘤的分类之间的一个重要协会。结论：L1 明确地在被知道有最糟的预后的糟糕区分的胰腺的神经内分泌癌被表示。L1 可能是为与胰腺的神经内分泌癌诊断的病人的风险预言的一个标记。

The role of LIN28B in tumor progression and metastasis in solid tumor entities

LIN28B is an RNA-binding protein that targets a broad range of microRNAs and modulates their maturation and activity.Under normal conditions,LIN28B is exclusively expressed in embryogenic stem cells,blocking differentiation and promoting proliferation.In addition,it can play a role in epithelial-to-mesenchymal transition by repressing the biogenesis of let-7 microRNAs.In malignancies,LIN28B is frequently overexpressed,which is associated with increased tumor aggressiveness and metastatic properties.In this review,we discuss the molecular mechanisms of LIN28B in promoting tumor progression and metastasis in solid tumor entities and its potential use as a clinical therapeutic target and biomarker.

Necrosis zone depth after bipolar plasma vaporization and resection in the human prostate

Objectives:To compare the depth of thermal necrosis after use of bipolar resection and vaporization technique comparing intra-individually bipolar loop and bipolar button electrodes.Methods:Transurethral resection and vaporization of the prostate was performed in 55 male patients(260 specimens in total).In a standardized procedure,a bipolar resection loop was used for resection,and a bipolar button electrode was used for vaporization.Both electrodes were applied in each patient,either in the left or in the right lateral lobe.The depth of necrotic zones in the resected or vaporized tissue of each patient was measured in a standardized way by light microscopy.Results:The mean depth with standard deviation of thermal injury caused by the loop electrode was 0.0495±0.0274 mm.The vaporization electrode caused a mean thermal depth with standard deviation of 0.0477±0.0276 mm.The mean difference of necrosis zone depths between the two types of electrodes(PlasmaButtoneresection loop)was 0.0018 mm(p=0.691).Conclusion:For the first time,we present directly measured values of the absolute necrosis zone depth after application of plasma in the transurethral treatment of benign prostatic hyperplasia.The measured values were lower than in all other transurethral procedures.Standardized procedures of measurement and evaluation allow a statistically significant statement that the low necrosis depth in bipolar procedures is independent of the applied electrodes.

Cyclosporine versus tacrolimus in patients with HCV infection after liver transplantation:Effects on virus replication and recurrent hepatitis

瞄准：决定 calcineurin 禁止者， cyclosporine 和 tacrolimus 的效果，在丙肝上，在病人的周期性的丙肝的病毒(HCV ) 复制和活动张贴肝移植。方法：在我们的中心为在 1999 和 2003 之间的联系 HCV 的肝肝硬化收到了肝移植的 107 个病人的一个队的数据回顾地被分析。浆液 HCV-RNA 的水平和周期性的肝炎的活动在作为主要抑制免疫力的代理人和没在移植以后在开始的 12 瞬间以内导致胆汁的复杂并发症的不那样类似的抑制免疫力的政体收到了 cyclosporine 或 tacrolimus 的 47 个病人之间被比较。结果：HCV-RNA 在移植以后在 3 瞬间以内增加了，但是 cyclosporine 组和 tacrolimus 组之间的差别是不足道的(在 12 瞬间的 P=0.49 ) 。另外，由浆液 transaminases 决定了的周期性的肝炎并且门发炎和纤维变性的组织学的分级没在 12 瞬间(P=0.34 ) 以后显示出有效差量。结论：一个主要抑制免疫力的代理人不在肝移植以后在感染 HCV 的病人影响周期性的肝炎的正式就职或严厉的 Cyclosporine 或 tacrolimus。

Development of early gastric cancer 4 and 5 years after complete remission of Helicobacter pyloriassociated gastric low-grade marginal zone B-cell lymphoma of MALT type

AIM To report 3 of 120 patients on the German MALT lymphoma trial with H. pYlori-associated gastric MALT Iymphoma who developed early gastric cancer 4 and 5 years, after complete Iymphoma remission following cure of H. pylori infection.PATIENTS AND RESULTS Three patients (two men, 74 and 70 years; one women, 77 years)with H. pylori -associated low-grade MALTlymphoma achieved complete lymphoma remission after being cured. Surveillance endoscopies were performed twice a year in accordance to the protocol. Four years aftercomplete lymphoma remission in two patients,and after 5 years in the other, early gastric adenocarcinoma of the mucosa-type, type Ⅱ a and type Ⅱ c, respectively, was detetcted,which were completely removed by endoscopic mucosa resection. in one patient, the gastric cancer was diagnosed at the same location as the previous. MALT lymphoma, in the other patients it was detected at different sites of the stomach distant from location of the previous MALT lymphoma. The patients were H. pylori negative during the whole follow-up time.CONCLUSION These findings strengthen the importance of regular long-term follow-up endoscopies in patients with complete remission of gastric MALT lymphoma after cure of H.pylori infection. Furthermore, gastric adenocarcinoma may develop despite eradication of H. pylori.

Predictive value of Ki67 and p53 in locally advanced rectal cancer:Correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy

AIM: To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase (TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuvant treatment regimen.METHODS: Formalin fixed, paraffin embedded pre-therapeutical tumor biopsies (n = 22) and post-therapeutical resection specimens (n = 40) from patients with rectal adenocarcinoma (clinical UICC stage Ⅱ/Ⅲ) receiving standardized neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy were studied for Ki67 and p53 expression by immunohistochemistry and correlated with TS mRNA expression by quantitative TaqMan real-time PCR after laser microdissection. The results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system.RESULTS: Responders (patients with high tumor regression) showed a significantly lower Ki67 expression than non-responders in the pre-therapeutical tumor biopsies (81.2% vs 16.7%; P < 0.05) as well as in the post-therapeutical resection specimens (75.8% vs 14.3%; P < 0.01). High TS mRNA expression was significantly correlated with a high Ki67 index and low TS mRNA expression was significantly correlated with a low Ki67 index in the pre-therapeutical tumor biopsies (corr. coef. = 0.46; P < 0.01) as well as in the post-therapeutical resection specimens (corr. coef. = 0.40; P < 0.05). No significant association was found between p53 and TS mRNA expression or tumor regression.CONCLUSION: Ki67 has, like TS, predictive value in rectal cancer patients after neoadjuvant 5-FU based chemoradiotherapy. The close correlation between Ki67 and TS indicates that TS is involved in active cell cycle processes.

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases

AIM:To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (PPARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD).METHODS:DNA from a total of 622 specimens including 259 blood samples of healthy blood donors and 363 histologically categorized liver biopsies of patients with NAFLD (n=263) and AFLD (n=100) were analyzed by Real-time polymerase chain reaction using allele-specific probes.RESULTS:In the NAFLD and the AFLD collective,3% of the patients showed homozygous occurrence of the Ala12 PPARγ2-allele,differing from only 1.5% cases in the healthy population.In NAFLD patients,a high incidence of the Ala12 mutant was not associated with the progression of fatty liver disease.However,we observed a significantly higher risk (odds ratio=2.50,CI:1.05-5.90,P=0.028) in AFLD patients carrying the mutated Ala12 allele to develop inflammatory alterations.The linkage of the malfunctioning Ala12-positive PPARγ2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of PPARγ2 in progression of AFLD than of NAFLD.CONCLUSION:In AFLD patients,the Pro12Ala single nuclear polymorphism should be studied more extensively in order to serve as a novel candidate in biomarker screening for improved prognosis.

Invasive front of colorectal cancer:Dynamic interface of pro-/anti-tumor factors

Tumor-host interaction at the invasive front of colorectal cancer represents a critical interface encompassing a dynamic process of de-differentiation of colorectal carci-noma cells known as epithelial mesenchymal transition (EMT). EMT can be identified histologically by the presence of "tumor budding" ,a feature which can be highly specific for tumors showing an inf iltrating tumor growth pattern. Importantly,tumor budding and tumor border configuration have generated considerable interest as additional prognostic factors and are also recognized as such by the International Union Against Cancer. Evidence seems to suggest that the presence of tumor budding or an infiltrating growth pattern is inversely correlated with the presence of immune and inflammatory responses at the invasive tumor front. In fact,several tumor-associated antigens such as CD3,CD4,CD8,CD20,Granzyme B,FOXP3 and other immunological or inflammatory cell types have been identified as poten-tially prognostic in patients with this disease. Evidence seems to suggest that the balance between protumor (including budding and inf iltrating growth pattern) and anti-tumor (immune response or certain inflammatory cell types) factors at the invasive front of colorectal cancer may be decisive in determining tumor progression and the clinical outcome of patients with colorectal cancer. On one hand,the inf iltrating tumor border configuration and tumor budding promote progression and dissemination of tumor cells by penetrating the vascular and lymphatic vessels. On the other,the host attempts to fend off this attack by mounting an immune response to protect vascular and lymphatic channels from invasion by tumor buds. Whereas standard pathology reporting of breast and prostate cancer involves additional prognostic features,such as the BRE and Gleason scores,the ratio of pro-and anti-tumor factors could be a promising approach for the future development of a prognostic score for patients with colorectal cancer which could complement tumor node metastasis staging to improve the clinical management of patients with this disease.

Therapy of gastric mucosa associated lymphoid tissue lymphoma

Gastric mucosa associated lymphoid tissue (MALT) lymphoma has recently been incorporated into the World Health Organization (WHO) lymphoma classification, termed as extranodal marginal zone B-cell lymphoma of MALT-type. In about 90% of cases this lymphoma is associated with H pylori infection which has been clearly shown to play a causative role in lymphomagenesis. Although much knowledge has been gained in defining the clinical features, natural history, pathology, and molecular genetics of the disease in the last decade, the optimal treatment approach for gastric MALT lymphomas, especially locally advanced cases, is still evolving. In this review we focus on data for the therapeutic, stage dependent management of gastric MALT lymphoma. Hence, the role of eradication therapy, surgery, chemotherapy and radiotherapy is critically analyzed. Based on these data, we suggest a therapeutic algorithm that might help to better stratify patients for optimal treatment success.

Local Proinflammatory Effects of Repeated Skin Exposure to Warfarin, An Anticoagulant Rodenticide in Rats

Objective： To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods： Rats were exposed to warfarin by applying 10 μg of warfarin‐sodium to 10‐12 cm 2 skin （range 0.8‐1 μg per 1 cm 2 ） for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results： Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury （increased malondialdehyde, MDA, production, evident histo‐morphological changes in epidermis and dermis depicting cell injury and death）. Increased numbers of proliferating cell nuclear antigen （PCNA ＋ ） cells indicated reparative processes in injured skin. Infiltration of CD3 ＋ cells （T lymphocytes） along with the increased production of tumor necrosis factor‐α （TNF‐α） by epidermal cells from warfarin‐treated skin and their co‐stimulatory effect in an in vitro T‐cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion： Presented data have documented tissue damage associated with immune/ inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.

Protective effects of ischemic preconditioning and application of lipoic acid prior to 90 min of hepatic ischemia in a rat model

AIM: To compare different preconditioning strategies to protect the liver from ischemia/reperfusion injury focusing on the expression of pro- and anti-apoptotic proteins. Interventions comprised different modes of ischemic preconditioning (IP) as well as pharmacologic pretreatment by α-lipoic acid (LA). METHODS: Several groups of rats were compared: sham operated animals, non-pretreated animals (nt), animals receiving IP (10 min of ischemia by clamping of the portal triad and 10 min of reperfusion) prior to sustained ischemia, animals receiving selective ischemic preconditioning (IPsel, 10 min of ischemia by selective clamping of the ischemic lobe and 10 min of reperfusion) prior to sustained ichemia, and animals receiving 500 μmol α-LA injected i.v. 15 min prior to the induction of 90 min of selective ischemia. RESULTS: Cellular damage was decreased only in the LA group. TUNEL-positive hepatocytes as well as necrotic hepatocyte injury were also decreased only by LA (19 ± 2 vs 10 ± 1, P < 0.05 and 29 ± 5 vs 12 ± 1, P < 0.05). Whereas caspase 3- activities in liver tissue were unchanged, caspase 9- activity in liver tissue was decreased only by LA pretreatment (3.1 ± 0.3 vs 1.8 ± 0.2, P < 0.05). Survival rate as the endpoint of liver function was increased after IP and LA pretreatment but not after IPsel. Levels of lipid peroxidation (LPO) in liver tissue were decreased in the IP as well as in the LA group compared to the nt group. Determination of pro- and anti-apoptotic proteins showed a shift towardsanti-apoptotic proteins by LA. In contrast, both our IP strategies failed to influence apototic cell death. CONCLUSION: IP, consisting of 10 min of ischemia and 10 min of reperfusion, protects only partly against ischemia/reperfusion injury of the liver prior to 90 min of selective ischemia. IPsel did not influence ischemic tolerance of the liver. LA improved tolerance to ischemia, possibly by downregulation of pro-apoptotic Bax.

Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients

AIM:To investigate whether the evaluation of tumor budding can complement K-RAS analysis to improve the individualized prediction of response to anti-epidermal growth factor receptor based therapies in metastatic colorectal cancer (mCRC) patients. METHODS:Forty-three patients with mCRC treated with cetuximab or panitumumab were entered into this study. According to the Response Evaluation Criteria in Solid Tumors criteria, 30 patients had stable or progressive disease (non-responsive), while 13 patients had a partial response. Tumor buds were evaluated from whole tissue sections stained for pan-cytokeratin, evaluated in the densest region using a 40 × objective and "high-grade" tumor budding was defi ned as 15 buds/high-power f ield.RESULTS: Tumor buds and K-RAS mutation both correctly classif ied 68% of patients. All patients with K-RAS mutation (n=7) or high-grade tumor budding (n=11) were non-responsive, of which 4 patients had both features. All 13 partial responders were K-RAS wild-type with low-grade tumor budding. Combined, the predictive value of K-RAS and tumor budding was 80%. Additionally, high-grade tumor budding was significantly related to worse progression-free survival [HR (95% CI): 2.8 (1.3-6.0, P=0.008)].CONCLUSION: If confirmed in larger cohorts, the addition of tumor budding to K-RAS analysis may represent an effective approach for individualized patient management in the metastatic setting.

Reduction of ischemia reperfusion injury after liver resection and hepatic inflow occlusion by α-lipoic acid in humans

AIM: To evaluate the protective effects of precondition- ing by α-lipoic acid (LA) in patients undergoing hepatic resection under inflow occlusion of the liver. METHODS: Twenty-four patients undergoing liver re- section for various reasons either received 600 mg LA or NaCl 15 min before transection performed under inflow occlusion of the liver. Blood samples and liver wedge bi- opsy samples were obtained after opening of the abdo- men immediately after inflow occlusion of the liver, and 30 min after the end of inflow occlusion of the liver. RESULTS: Serum levels of aspartate transferase and alanine transferase were reduced at all time points in patients who received LA in comparison to those who received NaCL. This was accompanied by reduced histo- morphological features of oncosis. We observed TUNEL- positive hepatocytes in the livers of the untreated patients, especially after 30 min of ischemia. LA attenu- ated this increase of TUNEL-positive hepatocytes. Under preconditioning with LA, ATP content was significantly enhanced after 30 min of ischemia and after 30 min of reperfusion. CONCLUSION: This is the first report on the poten- tial for LA reducing ischemia/reperfusion injury (IRI) of the liver in humans who were undergoing liver surgery. Beside its simple and rapid application, side effects did not occur. LA might therefore represent a new strategy against hepatic IRI in humans.

Is there an association of microscopic colitis and irritable bowel syndrome-A subgroup analysis of placebo-controlled trials

TO THE EDITOR With great interest we read the recent retrospectice study by Barta et al (1) dealing with the clinical presentation of patients with microscopic colitis. They investigated in a cohort of 53 patients with microscopic colitis (46 with collagenous colitis, 7 with lymphocytic colitis)the relationship between microscopic colitis and both constipation and diarrhea. One of their mean finding was that abdominal pain, diarrhea and constipation was a common symptom complex of patients with microscopic colitis, thus the face of microcopic colitis resembles the subgroups of irritable bowel syndrome (IBS).

Hepatitis C virus genotypes in Serbia and Montenegro: The prevalence and clinical signifi cance

AIM: To investigate the prevalence of hepatitis C virus (HCV) genotypes in Serbia and Montenegro and their in? uence on some clinical characteristics in patients with chronic HCV infection.METHODS: A total of 164 patients was investigated. Complete history, route of infection, assessment of al-cohol consumption, an abdominal ultrasound, standard biochemical tests and liver biopsy were done. Gene se-quencing of 5’ NTR type-specifi c PCR or commercial kits was performed for HCV genotyping and subtyping. The SPSS for Windows (version 10.0) was used for univariate regression analysis with further multivariate analysis. RESULTS: The genotypes 1, 2, 3, 4, 1b3a and 1b4 were present in 57.9%, 3.7%, 23.2%, 6.7%, 6.7% and 1.8% of the patients, respectively. The genotype 1 (mainly the subtype 1b) was found to be independent of age in sub-jects older than 40 years, high viral load, more severe necro-in? ammatory activity, advanced stage of fi brosis, and absence of intravenous drug abuse. The genotype 3a was associated with intravenous drug abuse and the age below 40. Multivariate analysis demonstrated age over 40 and intravenous drug abuse as the positive pre-dictive factors for the genotypes 1b and 3a, respectively. CONCLUSION: In Serbia and Montenegro, the geno-types 1b and 3a predominate in patients with chronic HCV infection. The subtype 1b is characteristic of older patients, while the genotype 3a is common in drug abus-ers. Association of the subtype 1b with advanced liverdisease, higher viral load and histological activity sug-gests earlier infection with this genotype and eventually its increased pathogenicity.

Pivotal role of long non-coding ribonucleic acid-X-inactive specific transcript in regulating immune checkpoint programmed death ligand 1 through a shared pathway between miR-194-5p and miR-155-5p in hepatocellular carcinoma

BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.

Helicobacter pylori and gastric cancer: current status of the Austrian-Czech-German gastric cancer prevention trial (PRISMA-Study)

AIM To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease.METHODS It is a prospective, randomized,double-blind, placebo-controlled multinational multicenter trial. Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacterpylori gastritis are randomized to receive a 7-day course of omeprazole 2 × 20 mg,clarithromycin 2 × 500 mg, and amoxicillin 2 ×lg for 7 days, or omeprazole2 × 20mg plusplacebo. Follow - up endoscopy is scheduled 3months after therapy, and thereafter in one-year intervals. Predefined study endpoints are gastric cancer, precancerous lesions (dysplasia, adenoma), other cancers, anddeath.RESULTS Since March 1998, 1524 target patients have been screened, 279 patients (18.3%) had a corpus-dominant type of H.pylori gastritis, and 167 of those were randomized (58.8%). In the active treatment group (n -- 86), H. pylori infection infection was cured in 88.9% of patients. Currently, thecumulative follow-up time is 3046 months (253.8patient-years, median follow-up 16 months). So far, none of the patients developed gastric cancer or any precancerous lesion. Three(1.8%) patients reached study endpoints other than gastric cancer.CONCLUSION Among men between 55 and 65years of age, the gastric cancer phenotype of H.pylori gastritis appears to be more common than expected. Further follow- up and continuing recruitment are necessary to fulfil the main aim of the study.