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https://www.readbyqxmd.com/read/28535453/inhibition-of-neddylation-modification-sensitizes-pancreatic-cancer-cells-to-gemcitabine
#1
Hua Li, Weihua Zhou, Lihui Li, Jianfu Wu, Xiaoli Liu, Lili Zhao, Lijun Jia, Yi Sun
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA with a 5-year survival rate less than 3% to 5%. Gemcitabine remains as a standard care for PDAC patients. Although protein neddylation is abnormally activated in many human cancers, whether neddylation dysregulation is involved in PDAC and whether targeting neddylation would sensitize pancreatic cancer cells to gemcitabine remain elusive. Here we report that high expression of neddylation components, NEDD8 and NAE1, are associated with poor survival of PDAC patients...
May 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28535439/critical-focus-on-mechanisms-of-resistance-and-toxicity-of-m-tor-inhibitors-in-pancreatic-neuroendocrine-tumors
#2
REVIEW
L Antonuzzo, M Del Re, V Barucca, F Spada, G Meoni, G Restante, R Danesi, F Di Costanzo, N Fazio
Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms representing less than 2% of all pancreatic malignancies. The PI3K-AKT-mTOR pathway is often deregulated in pNETs and seems to play a key role in tumorigenesis. Everolimus, an inhibitor of the mTOR pathway, has demonstrated efficacy in the treatment of pNETs. Nevertheless de novo or acquired drug resistance is responsible for disease progression and represents a major obstacle to overcome by clinicians. Blocking the PI3K/AKT/mTOR pathway may cover the supposed main mechanisms of resistance to everolimus...
May 11, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28535431/partial-ablation-of-the-pancreas-of-sprague-dawley%C3%A2-rats-by-focused-ultrasound-reveals-no-significant-adverse-effects-on-glycometabolism-function
#3
Lan Ao, Na Hu, Hai Xia Hu, Qing Liu, Zi Hao Zhao, Long Xing Liu, Jun Ru Wu, Fa Qi Li, Liao Qiong Fang
To investigate the safety of focused ultrasound (FUS) partial ablation on the pancreas of Sprague Dawley® (SD) rats by histopathological examination of the outcome and investigation of glycometabolism function changes after local ablation. A total of 135 healthy SD rats were randomly divided into three groups (n=45 of each): FUS ½ group, FUS ¼ group, and control group. Levels of serum amylase was measured using the enzyme dynamics method, fasting blood glucose was measured by the glucose oxidase-peroxidase method, fasting serum insulin was measured by direct chemiluminescence assay, and an ELISA was used to measure fasting serum glucagon immediately after treatment, and at 2h, 3days, 1, 2, 3 and 4weeks, 3 and 6months after FUS ablation...
May 11, 2017: Ultrasonics
https://www.readbyqxmd.com/read/28535157/a-meta-analysis-of-cxcl12-expression-for-cancer-prognosis
#4
Harsh Samarendra, Keaton Jones, Tatjana Petrinic, Michael A Silva, Srikanth Reddy, Zahir Soonawalla, Alex Gordon-Weeks
BACKGROUND: CXCL12 (SDF1) is reported to promote cancer progression in several preclinical models and this is corroborated by the analysis of human tissue specimens. However, the relationship between CXCL12 expression and cancer survival has not been systematically assessed. METHODS: We conducted a systematic review and meta-analysis of studies that evaluated the association between CXCL12 expression and cancer survival. RESULTS: Thirty-eight studies inclusive of 5807 patients were included in the analysis of overall, recurrence-free or cancer-specific survival, the majority of which were retrospective...
May 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28535085/characterization-of-an-encapsulated-insulin-secreting-human-pancreatic-beta-cell-line-in-a-modular-microfluidic-device
#5
Argia Acarregui, Jesús Ciriza, Laura Saenz Del Burgo, Haritz Gurruchaga, José Yeste, Xavier Illa, Gorka Orive, Rosa M Hernández, Rosa Villa, Jose Luis Pedraz
Type I diabetes mellitus is characterized by the destruction of the insulin producing beta cells within the pancreas by the immune system. After the success of Edmonton protocol, islet transplantation has shown to be a promising therapy, but with the Achilles´ heel of the need of using immunosuppressive drugs. Currently, cell encapsulation technology represents a real alternative to protect transplanted islets from the host´s immune attack. Although preliminary in vitro studies with encapsulated cells have been traditionally performed under static conditions in terms of viability and efficiency, these static cultures do not represent a close approach to in vivo environments...
May 23, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28534950/microrna%C3%A2-296-targets-akt2-in-pancreatic-cancer-and-functions-as-a-potential-tumor-suppressor
#6
Hailing Li, Jilin Li, Baolin Shi, Feng Chen
Although microRNA-296 (miR-296) has been studied in various types of human cancer, its expression, biological role and mechanism of action in pancreatic cancer remains to be elucidated. The aim of the current study was to investigate the expression level, possible roles and underlying molecular mechanisms of miR‑296 in pancreatic cancer. The present study revealed that miR‑296 is significantly downregulated in tissue from patients with pancreatic cancer and in human pancreatic carcinoma cell lines, when compared with matched healthy tissue and normal human pancreatic cell lines, respectively...
May 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534945/trb3-mediates-advanced-glycation-end-product-induced-apoptosis-of-pancreatic-%C3%AE-cells-through-the-protein-kinase-c-%C3%AE-pathway
#7
Meng Wang, Wenjian Zhang, Shiqing Xu, Liang Peng, Zai Wang, Honglin Liu, Qing Fang, Tingting Deng, Xiuli Men, Jinning Lou
Advanced glycation end products (AGEs), which accumulate in the body during the development of diabetes, may be one of the factors leading to pancreatic β-cell failure and reduced β-cell mass. However, the mechanisms responsible for AGE‑induced apoptosis remain unclear. This study identified the role and mechanisms of action of tribbles homolog 3 (TRB3) in AGE-induced β-cell oxidative damage and apoptosis. Rat insulinoma cells (INS-1) were treated with 200 µg/ml AGEs for 48 h, and cell apoptosis was then detected by TUNEL staining and flow cytometry...
May 16, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534865/the-impact-of-smad4-loss-on-outcome-in-patients-with-advanced-pancreatic-cancer-treated-with-systemic-chemotherapy
#8
Steffen Ormanns, Michael Haas, Anna Remold, Stephan Kruger, Stefan Holdenrieder, Thomas Kirchner, Volker Heinemann, Stefan Boeck
The role of the tumor suppressor mothers against decapentaplegic homolog 4 (SMAD4) has not yet been defined in patients (pts) with advanced pancreatic cancer (aPC). This translational research study was designed to evaluate the impact of tumoral SMAD4 loss on clinicopathological parameters and outcome in PC patients receiving palliative chemotherapy. Using immunohistochemistry, we examined SMAD4 expression in tumor tissue of 143 aPC pts treated within completed prospective clinical and biomarker trials. In uni- and multivariate analyses, SMAD4 expression status was correlated to clinicopathological patient characteristics and outcome...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28534807/lobophorin-k-a-new-natural-product-with-cytotoxic-activity-produced-by-streptomyces-sp-m-207-associated-with-the-deep-sea-coral-lophelia-pertusa
#9
Alfredo F Braña, Aida Sarmiento-Vizcaíno, Miguel Osset, Ignacio Pérez-Victoria, Jesús Martín, Nuria de Pedro, Mercedes de la Cruz, Caridad Díaz, Francisca Vicente, Fernando Reyes, Luis A García, Gloria Blanco
The present article describes the isolation of a new natural product of the lobophorin family, designated as lobophorin K (1), from cultures of the marine actinobacteria Streptomyces sp. M-207, previously isolated from the cold-water coral Lophelia pertusa collected at 1800 m depth during an expedition to the submarine Avilés Canyon. Its structure was determined using a combination of spectroscopic techniques, mainly ESI-TOF MS and 1D and 2D NMR. This new natural product displayed cytotoxic activity against two human tumor cell lines, such as pancreatic carcinoma (MiaPaca-2) and breast adenocarcinoma (MCF-7)...
May 19, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28534552/-perforations-following-endoscopic-retrograde-cholangiopancreatography-ercp
#10
J Mateo Retuerta, C Chaveli Díaz, A Goikoetxea Urdiain, B Sainz Villacampa, M J Sara Ongay, J J Íñigo Noain
Endoscopic retrograde cholangiopancreatography (ERCP) associated with sphincterotomy is a useful procedure that is widely used in cases of choledocholithiasis and bile duct obstruction. In spite of being a safe test, there is a risk of complications like pancreatitis, haemorrhaging or perforation. Post-ERCP duodenal perforation is a rare event but has serious consequences if it is not treated early. The lesion mechanism, the place and extension of the perforation, as well as the clinical picture and radiographic findings will guide patient management, which must be individualised and constantly reevaluated...
April 30, 2017: Anales del Sistema Sanitario de Navarra
https://www.readbyqxmd.com/read/28534524/competing-risks-for-mortality-in-patients-with-asymptomatic-pancreatic-cystic-neoplasms-implications-for-clinical-management
#11
Karl Kwok, Jonathan Chang, Lewei Duan, Brian Z Huang, Bechien U Wu
OBJECTIVES: Pancreatic cystic neoplasms (PCNs) are being detected with increased frequency. Current clinical practice guidelines emphasize management based on cyst-related features. We aimed to evaluate the impact of comorbidity on mortality in PCN patients via competing risk analysis. METHODS: We analyzed a retrospective cohort of patients diagnosed between 2005-2010, with follow-up through 2015, for overall and cause-specific mortality. Comorbidities were classified by the Charlson comorbidity index...
May 23, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28534517/prolonged-exposure-to-extracellular-lumican-restrains-pancreatic-adenocarcinoma-growth
#12
X Li, Y Kang, D Roife, Y Lee, M Pratt, M R Perez, B Dai, E J Koay, J B Fleming
We previously demonstrated that pancreatic stellate cells within pancreatic ductal adenocarcinoma (PDAC) stroma secrete lumican and its presence is associated with prolonged survival of patients with localized PDAC. Here, we observed that extracellular lumican decreases PDAC tumour cell growth in xenograft and syngeneic orthotopic animal models, and induces growth inhibition of low-passage human PDAC cells in a species-specific manner. PDAC cells grown in variant culture conditions and exposed to extracellular lumican display typical characterizations of cancer cell in a quiescent state, such as growth inhibition, apoptosis, G0/G1 arrest and chemoresistance...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534439/hypolipidemic-and-hepatoprotective-activities-of-rosemary-and-thyme-in-gentamicin-treated-rats
#13
A M Hegazy, A S Abdel-Azeem, H M Zeidan, K S Ibrahim, Em El Sayed
Rosemary ( Rosmarinus officinalis; RM) and thyme ( Thymus vulgaris; TV) are used as remedies. We designed this work to investigate the preventive effect of aqueous extracts of RM or TV on the gentamicin (GM)-induced hepatotoxicity and abnormalities of lipid profile in rats. Both plant extracts exhibited an in vitro antioxidant activity as determined by the 1,1-diphenyl-2-picrylhydrazyl assay. Radical scavenging activity for TV extract was 48.7% and for RM extract was 25.6%. Polyphenolic determination by high-performance liquid chromatography for both extracts revealed that catechin, coumarin, cinnamic acid and rutin were detected in both extracts...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28534223/immunoglobulin-m-gene-association-with-autoantibody-reactivity-and-type-1-diabetes
#14
Inês Rolim, Nádia Duarte, Gabriela Barata, João Costa, Luís Gardete-Correia, José Boavida, Rui Duarte, João Raposo, Zulmira Peerally, Manuela Catarino, Carlos Penha-Gonçalves
Several lines of evidence show that autoimmune responses evolving in type 1 diabetes (T1D) patients include the generation of multi-reactive autoantibody (AutoAb) repertoires, but their role in T1D pathogenesis remains elusive. We tested the hypothesis that variants at the immunoglobulin heavy chain (IGH) locus are genetic determinants of AutoAbs against pancreatic antigens and contribute to T1D susceptibility. With this aim, two independent study designs were used: a case-control study and a family-based cohort comprising a total of 240 T1D patients, 172 first-degree relatives (mother and/or father), and 130 unrelated healthy controls living in Portugal...
May 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28534195/identification-of-a-small-molecule-that-facilitates-the-differentiation-of-human-ipscs-escs-and-mouse-embryonic-pancreatic-explants-into-pancreatic-endocrine-cells
#15
Yasushi Kondo, Taro Toyoda, Ryo Ito, Michinori Funato, Yoshiya Hosokawa, Satoshi Matsui, Tomomi Sudo, Masahiro Nakamura, Chihiro Okada, Xiaotong Zhuang, Akira Watanabe, Akira Ohta, Nobuya Inagaki, Kenji Osafune
AIMS/HYPOTHESIS: Pancreatic beta-like cells generated from human induced pluripotent stem cells (hiPSCs) or human embryonic stem cells (hESCs) offer an appealing donor tissue source. However, differentiation protocols that mainly use growth factors are costly. Therefore, in this study, we aimed to establish efficient differentiation protocols to change hiPSCs/hESCs to insulin (INS)(+) cells using novel small-molecule inducers. METHODS: We screened small molecules that increased the induction rate of INS(+) cells from hESC-derived pancreatic and duodenal homeobox 1 (PDX1)(+) pancreatic progenitor cells...
May 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28534079/failure-to-treat-audit-of-an-institutional-cancer-registry-database-at-a-large-comprehensive-cancer-center-reveals-factors-affecting-the-treatment-of-pancreatic-cancer
#16
Jennifer L Miller-Ocuin, Mazen S Zenati, Lee M Ocuin, Patrick R Varley, Stephanie M Novak, Sharon Winters, Amer H Zureikat, Herbert J Zeh, Melissa E Hogg
BACKGROUND: National Cancer Database analysis showed 70% of patients with stage I pancreatic adenocarcinoma (PDA) did not have surgery. We sought to analyze adherence to expected treatment (ET) by stage for PDA and identify factors that led to no treatment (NT) or unexpected treatment (UT) in a recent cohort. METHODS: Using our Institutional Cancer Registry (ICR), we identified patients with PDA from 2004 to 2013. ET was defined as surgery ± chemotherapy ± radiation for stages I and II, chemotherapy ± radiation for stage III, and chemotherapy for stage IV, while UT was defined as no surgery for stages I and II, surgery for stage III, or ± surgery ± XRT for stage IV...
May 22, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28533675/comparison-of-endoscopic-ultrasound-computed-tomography-and-magnetic-resonance-imaging-in-assessment-of-detailed-structures-of-pancreatic-cystic-neoplasms
#17
Chen Du, Ning-Li Chai, En-Qiang Linghu, Hui-Kai Li, Li-Hua Sun, Lei Jiang, Xiang-Dong Wang, Ping Tang, Jing Yang
AIM: To evaluate the advantages of endoscopic ultrasound (EUS) in the assessment of detailed structures of pancreatic cystic neoplasms (PCNs) compared to computed tomography (CT) and magnetic resonance imaging (MRI). METHODS: All patients with indeterminate PCNs underwent CT, MRI, and EUS. The detailed information, including size, number, the presence of a papilla/nodule, the presence of a septum, and the morphology of the pancreatic duct of PCNs were compared among the three imaging modalities...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28533671/consequences-of-metabolic-syndrome-on-postoperative-outcomes-after-pancreaticoduodenectomy
#18
Alban Zarzavadjian Le Bian, David Fuks, Sophie Chopinet, Sébastien Gaujoux, Manuela Cesaretti, Renato Costi, Ajay P Belgaumkar, Claude Smadja, Brice Gayet
AIM: To analyze immediate postoperative outcomes after pancreaticoduodenectomy regarding metabolic syndrome. METHODS: In two academic centers, postoperative outcomes of patients undergoing pancreaticoduodenectomy from 2002 to 2014 were prospectively recorded. Patients presenting with metabolic syndrome [defined as at least three criteria among overweight (BMI ≥ 28 kg/m²), diabetes mellitus, arterial hypertension and dyslipidemia] were compared to patients without metabolic syndrome...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28533666/comparison-of-imaging-based-and-pathological-dimensions-in-pancreatic-neuroendocrine-tumors
#19
Salvatore Paiella, Harmony Impellizzeri, Elisabetta Zanolin, Giovanni Marchegiani, Marco Miotto, Anna Malpaga, Riccardo De Robertis, Mirko D'Onofrio, Borislav Rusev, Paola Capelli, Sara Cingarlini, Giovanni Butturini, Maria Vittoria Davì, Antonio Amodio, Claudio Bassi, Aldo Scarpa, Roberto Salvia, Luca Landoni
AIM: To establish the ability of magnetic resonance (MR) and computer tomography (CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors (PanNET) in a caseload of a tertiary referral center. METHODS: Patients submitted to surgery for PanNET at the Surgical Unit of the Pancreas Institute with at least 1 preoperative imaging examination (MR or CT scan) from January 2005 to December 2015 were included and data retrospectively collected. Exclusion criteria were: multifocal lesions, genetic syndromes, microadenomas or mixed tumors, metastatic disease and neoadjuvant therapy...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28533664/pancreaticoduodenectomy-in-patients-%C3%A2-75-years-of-age-are-there-any-differences-with-other-age-ranges-in-oncological-and-surgical-outcomes-results-from-a-tertiary-referral-center
#20
Salvatore Paiella, Matteo De Pastena, Tommaso Pollini, Giovanni Zancan, Debora Ciprani, Giulia De Marchi, Luca Landoni, Alessandro Esposito, Luca Casetti, Giuseppe Malleo, Giovanni Marchegiani, Massimiliano Tuveri, Enrico Marrano, Laura Maggino, Erica Secchettin, Deborah Bonamini, Claudio Bassi, Roberto Salvia
AIM: To compare surgical and oncological outcomes after pancreaticoduodenectomy (PD) in patients ≥ 75 years of age with two younger cohorts of patients. METHODS: The prospectively maintained Institutional database of pancreatic resection was queried for patients aged ≥ 75 years (late elderly, LE) submitted to PD for any disease from January 2010 to June 2015. We compared clinical, demographic and pathological features and survival outcomes of LE patients with 2 exact matched cohorts of younger patients [≥ 40 to 64 years of age (adults, A) and ≥ 65 to 74 years of age (young elderly, YE)] submitted to PD, according to selected variables...
May 7, 2017: World Journal of Gastroenterology: WJG
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