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| 1 | Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25显示文摘堵住抗体 ipilimumab 的细胞毒素的 T 淋巴细胞 antigen-4 (CTLA-4 ) 在很少的病人导致变形黑瘤的调停免疫者的长期的控制。尽管 ipilimumab 无疑经由 immunostimulation 施加它的治疗学的效果,这样远的临床上有用的、 immunologically 相关的 biomarkers 预言治疗效率是逃犯的。这里,我们显示出 IL-2 的那中立化或堵住 α并且 βIL-2 受体的子单元(CD25 和 CD122,分别地) 否则在现出症状之前的潜的老鼠模型由 CTLA-4 封锁导致了,废除了 antitumor 效果和 intratumoral T 受动器对规章的房间(Tregs ) 的比率的伴随的改进,它是。CTLA-4 封锁导致了在失去了 FoxP3 表示并且在 regressing 肿瘤积累了的 IL-2-producing 受动器房间与伴随物上升表示 Lag3, ICOS, IL-10 和 Egr2 的一个镇压 CD4 + T 房间子集的减小。当 recombinant IL-2 改进了 CTLA-4 封锁的治疗学的功效时,圈套 IL-2 受体 α(IL-2Rα, sCD25 ) 禁止了 CTLA-4 的 anticancer 效果封锁。在收到 ipilimumab 的 262 个变形黑瘤病人, sCD25 的基线浆液集中代表了全面幸存的独立指示物,与预言到治疗的抵抗的高水平。总的来说,这些结果解开为在 CTLA-4 的 anticancer 活动的 IL-2 和 IL-2 受体的一个角色封锁。重要地,我们的学习提供第一 immunologically 相关的 biomarker,也就是提高的浆液 sCD25,那与黑瘤在病人预言抵抗到 CTLA-4 封锁。 | Dalil Hannani Marie Vetizou David Enot Sylvie Rusakiewicz Nathalie Chaput David Klatzmann Melanie Desbois Nicolas Jacquelot Nadege Vimond Salem Chouaib Christine Mateus James P Allison Antoni Ribas Jedd D Wolchok Jianda Yuan Philip Wong Michael Postow Andrzej Mackiewicz Jacek Mackiewicz Dirk Schadendorff Dirk Jaeger Alan J Korman Keith Bahjat Michele Maio Luana Calabro Michele WL Teng Mark J Smyth Alexander Eggennont Caroline Robert Guido Kroemer Laurence Zitvogel | 2015 | Cell Research2015，25，2： | 14 |
| 2 | Negative capsule endoscopy in patients with obscure gastrointestinal bleeding reliable: Recurrence of bleeding on long-term follow-up显示文摘AIM: To assess the rate of recurrent bleeding of the small bowel in patients with obscure bleeding already undergone capsule endoscopy (CE) with negative results. METHODS: We reviewed the medical records related to 696 consecutive CE performed from December 2002 to January 2011, focusing our attention on patients with recurrence of obscure bleeding and negative CE. Evaluating the patient follow-up, we analyzed the recurrence rate of obscure bleeding in patient with a negative CE. Actuarial rates of rebleeding during follow-up were calculated, and factors associated with rebleeding were assessed through an univariate and multivariate analysis. A P value of less than 0.05 was regarded as statistically significant. The sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of negative CE were calculated. RESULTS: Two hundred and seven out of 696 (29.7%) CE studies resulted negative in patient with obscure/overt gastrointestinal bleeding. Overall, 489 CE (70.2%) were positive studies. The median follow-up was 24 mo (range 12-36 mo). During follow-up, recurrence of obscure bleeding was observed only in 34 out of 207 negative CE patients (16.4%); 26 out of 34 with obscure overt bleeding and 8 out of 34 with obscure occult bleeding. The younger age (< 65 years) and the onset of bleeding such as melena are independent risk factors of rebleeding after a negative CE (OR = 2.6703, 95%CI: 1.1651-6.1202, P = 0.0203; OR 4.7718, 95%CI: 1.9739-11.5350, P = 0.0005). The rebleeding rate (CE+ vs CE-) was 16.4% vs 45.1% (χ 2 test, P = 0.00001). The sensitivity, specificity, and PPV and NPV were 93.8%, 100%, 100%, 80.1%, respectively. CONCLUSION: Patients with obscure gastrointestinal bleeding and negative CE had a significantly lower rebleeding rate, and further invasive investigations can be deferred. | Maria Elena Riccioni Riccardo Urgesi Rossella Cianci Gianluca Rizzo Luca D'Angelo Riccardo Marmo Guido Costamagna | 2013 | World Journal of Gastroenterology2013，19，28： | 14 |
| 3 | Nano albumin bound-paclitaxel in pancreatic cancer: Current evidences and future directions显示文摘Pancreatic cancer(PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor. Recently PDAC stroma has been addressed as a potential therapeutic target. Nano albumin bound(Nab)-paclitaxel is an innovative molecule depleting tumor stroma, through interaction between albumin and secreted protein acidic and rich in cysteine. Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate vs gemcitabine alone in the MPACT phase Ⅲ study. This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules. Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC. In this article, we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research. Furthermore, we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials. | Guido Giordano Massimo Pancione Nunzio Olivieri Pietro Parcesepe Marianna Velocci Tania Di Raimo Luigi Coppola Giuseppe Toffoli Mario Rosario D’Andrea | 2017 | World Journal of Gastroenterology2017，23，32： | 7 |
| 4 | Bcl-2 degradation is an additional pro-apoptotic effect of polo-like kinase inhibition in cholangiocarcinoma cells显示文摘AIM To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeuticallyapproach for cholangiocellular cancer treatment. METHODS As most cholangiocarcinomas are chemotherapyresistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma(CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases(PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators. Here, cells were treated with PLK inhibitor BI6727(Volasertib), Cisplatin, and in combination of both compounds. Cell viability was assessed by MTT; apoptosis was measured by DAPI staining and caspase-3/-7 assay. Western blot and q RT-PCR were used to measure expression levels of apoptosis-related molecules Bax and Bcl-2. RESULTS The cell viability in the CCA cell lines KMCH-1 and Mz-Ch-1 was reduced in all treatment conditions compared to vehicle-treated cells. Co-treatment with BI6727 and cisplatin could even enhance the cytotoxic effect of cisplatin single treatment. Thus, co-treatment of cisplatin with BI6727 could slightly enhance the cytotoxic effect of the cisplatin in both cell lines whereas there was evidence of increased apoptosis induction solely in Mz-Ch-1 as compared to KMCH-1. Moreover, PLK inhibition decreases protein levels of Bcl-2; an effect that can be reversed by the proteasomal degradation inhibitor MG-132. In contrast, protein levels of Bax were not found to be altered by PLK inhibition. These findings indicate that cytotoxic effects of Cisplatin in Mz-Ch-1 cells can be enhanced by co-treatment with BI6727.CONCLUSION In conclusion, BI6727 treatment can sensitize CCA cells to cisplatin-induced apoptosis with proteasomal Bcl-2 degradation as an additional pro-apoptotic effect. | Svenja Sydor Sami Jafoui Lena Wingerter Sandra Swoboda Joachim C Mertens Guido Gerken Ali Canbay Andreas Paul Christian D Fingas | 2017 | World Journal of Gastroenterology2017，23，22： | 5 |
| 5 | 22-gauge core vs 22-gauge aspiration needle for endoscopic ultrasound-guided sampling of abdominal masses显示文摘AIM To compare the aspiration needle(AN) and core biopsy needle(PC) in endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) of abdominal masses.METHODS Consecutive patients referred for EUS-FNA were included in this prospective single-center trial. Each patient underwent a puncture of the lesion with both standard 22-gauge(G) AN(Echo Tip Ultra; Cook Medical, Bloomington, Indiana, United States) and the novel 22 G PC(Echo Tip Pro Core; Cook Medical, Bloomington, Indiana, United States) in a randomized fashion; histology was attempted in the PC group only. The main study endpoint was the overall diagnostic accuracy, including the contribution of histology to the final diagnosis. Secondary outcome measures included material adequacy, number of needle passes, and complications.RESULTS Fifty six consecutive patients(29 men; mean age 68 years) with pancreatic lesions(n = 38), lymphadenopathy(n = 13), submucosal tumors(n = 4), or others lesions(n = 1) underwent EUS-FNA using both of the needles in a randomized order. AN and PC reached similar overall results for diagnostic accuracy(AN: 88.9 vs PC: 96.1, P = 0.25), specimen adequacy(AN: 96.4% vs PC: 91.1%, P = 0.38), mean number of passes(AN: 1.5 vs PC: 1.7, P = 0.14), mean cellularity score(AN: 1.7 vs PC: 1.1, P = 0.058), and complications(none). A diagnosis on the basis of histology was achieved in the PC group in 36(64.3%) patients, and in 2 of those as the sole modality. In patients with available histology the mean cellularity score was higher for AN(AN: 1.7 vs PC: 1.0, P = 0.034); no other differences were of statistical significance.CONCLUSION Both needles achieved high overall diagnostic yields and similar performance characteristics for cytological diagnosis; histological analysis was only possible in 2/3 of cases with the new needle. | William Sterlacci Athanasios D Sioulas Lothar Veits Pervin G?nüllü Guido Schachschal Stefan Groth Mario Anders Christos K Kontos Theodoros Topalidis Andrea Hinsch Michael Vieth Thomas R?sch Ulrike W Denzer | 2016 | World Journal of Gastroenterology2016，22，39： | 2 |
| 6 | Prospective evaluation of the short access cholangioscopy for stone clearance and evaluation of indeterminate strictures显示文摘BACKGROUND: Peroral cholangioscopy facilitates diagnosis and therapy of biliary disorders. This study prospectively evaluated a new short access cholangioscopy. METHODS: Consecutive patients were included as follows: difficult stones(group 1) underwent cholangioscopy with electrohydraulic lithotripsy and indeterminate biliary strictures(group 2) were evaluated with macroscopic assessment and cholangioscopy guided biopsy sampling. We evaluated the complete stone clearance rate(group 1) and diagnostic accuracy(group 2). Follow-up was performed over a median of 13 and 16 months, respectively.RESULTS: Group 1(n=21): complete stone clearance defined as lack of stones in cholangiography and stone removal during cholangioscopy was achieved in 15(71.4%) patients. Clinical stone clearance defined as lack of symptoms, laboratory abnormalities and hospital visits during follow-up, irrespective of stone clearance was evident in 17(81.0%) patients. One serious adverse event occurred(bile duct perforation). Group 2(n=28): malignancy was confirmed in 15 patients. Sensitivity, specificity and diagnostic accuracy of cholangioscopy were 85.7%, 75.0% and 80.7%, respectively. Sensitivity, specificity and diagnostic accuracy of biopsies were 54.5%, 100.0% and 72.2%, respectively. No serious adverse events occurred, and one patient was lost to follow-up.CONCLUSIONS: The novel system enabled complex stone treatment and biliary stricture diagnosis. Cholangioscopy outperformed direct biopsy regarding characterization of indeterminate strictures. | Athanasios D Sioulas Muhammad A El-Masry Stefan Groth Guido Schachschal Mario Anders Thomas Rosch Ulrike Denzer | 2017 | Hepatobiliary & Pancreatic Diseases International2017，16，1： | 2 |
| 7 | Characterization of flavonoids in cranberry (Vaccinium macrocarpon) powder显示文摘 | VVEDENSKAYA I O ROSEN R T GUIDO J E RUSSELL D J MILLS K A VORSA N | 2004 | Journal of Agricultural and Food Chemistry2004，52，： | 1 |
| 8 | The epidemic of antibiot-ic-resistant infections: a call to action for the medical communityfrom the Infectious Diseases Society of America 显示文摘 | Spellbei^ B Guidos R Gildert D etal | 2008 | Clin InfectDis2008，46，2： | 1 |
| 9 | Endoscopic ultrasound-guided fine needle aspiration with 22- and 25-gauge needles in solid pancreatic masses: A prospective comparative study with randomisation of needle sequence显示文摘 | Carlo Fabbri Anna Maria Polifemo Carmelo Luigiano Vincenzo Cennamo Paola Baccarini Guido Collina Adele Fornelli Sandro Macchia Nicola Zanini Elio Jovine Marta Fiscaletti Angela Alibrandi Nicola D’Imperio | 2011 | Digestive and Liver Disease2011，，8： | 1 |
| 10 | Ablation of Ca~(2+)channel beta3subunit leads to enhanced N-methyl-D-aspartate receptor dependent long term potentiation and improved long term memory显示文摘 | Jeon D Song 1 Guido W | 2008 | J Biol Chem2008，283，12： | 1 |
| 11 | Human papillomavirus teating following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease显示文摘 | Kreimer AR Guido RS Solomon D | 2006 | Cancer Epidemiol Biomarkers Prev2006，15，5： | 1 |
| 12 | Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease显示文摘 | Kreimer AR Guido RS Solomon D | 2006 | Cancer Epidemiol Biomarkers Prev2006，15，5： | 1 |
| 13 | A path model of sarcopenia on bone mass loss in elderly subjects 显示文摘 | Rondanelli M Guido D Opizzi A | 2014 | J Nutr Health Aging2014，18，1： | 1 |
| 14 | Damage Detection of a Prestressed Concrete Beam Using Modal Strains 显示文摘 | Jtirg F U Anne T Guido D R | 2005 | Journal of Structural Engineering2005，131，9： | 1 |
| 15 | Synthesis of 2-Amino-5- Sulfanyl-1,3,4-Thiadiazole Derivatives and Evaluation of Their Antidepressant and Anxiolytic Activity 显示文摘 | Clerici F Pocar D Guido M | 2001 | J Med Chem2001，44，6： | 1 |
| 16 | Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4^sup +^ T cell loss is associated with double-negative T cells显示文摘 | Milush Jeffrey M Mir Kiran D Sundaravaradan Vasudha Gordon Shari N Engram Jessica Cano Christopher A Reeves Jacqueline F Anton Elizabeth O’Neill Eduardo Butler Eboneé Hancock Kathy Cole Kelly S Brenchley Jason M Else James G Silvestri Guido | 2011 | Journal of Clinical Investigation2011，，3： | 1 |
| 17 | Arterivirus discontinuous mRNA transcription is guided by base pairing between sense and antisense transcription-regulating sequences显示文摘 | Guido van M Jessika C D Alexander P G | 1999 | Proc Natl Acad Sci USA1999，96，12： | 1 |
| 18 | Noise analysis of conventional and gain-clamped semiconductor optical amplifiers 显示文摘 | Guido G Davide D A | 2000 | IEEE Journal of Lightwave Technology2000，18，9： | 1 |
| 19 | Combating antimicrobial resistance: policy recommendations to save lives 显示文摘 | Infectious Diseases Society of America (IDSA) Spellberg B Blaser M Guidos RJ Boucher HW Bradley JS Eisenstein BI Gerding D Lynfield R Relier LB Rex J Schwartz D Septimus E Tenover FC Gilbert DN | 2011 | Clin Infect Dis2011，52，5： | 1 |
| 20 | Shale Gas: Applying Technology to Solve America' s Energy Challenges显示文摘 | Christopher A S Guido D J John R D | 2011 | National Energy Technology Laboratory2011，，3： | 1 |
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