Search results for "PDAC"

showing 8 items of 18 documents

Abilities of berberine and chemically modified berberines to inhibit proliferation of pancreatic cancer cells.

2018

Berberine (BBR) is a common nutraceutical consumed by millions worldwide. BBR has many different effects on human health, e.g., diabetes, diarrhea, inflammation and now more recently it has been proposed to have potent anti-cancer effects. BBR has been shown to suppress the growth of cancer cells more than normal cells. BBR has been proposed to exert its growth-inhibitory effects by many different biochemical mechanisms including: suppression of cell cycle progression, induction of reactive oxygen species, induction of apoptosis and autophagy and interactions with DNA potentially leading to DNA damage, and altered gene expression. Pancreatic cancer is a leading cancer worldwide associated w…

Male0301 basic medicineCancer ResearchSettore MED/09 - Medicina InternaBerberineDNA damagePopulationSignal transduction inhibitorsApoptosisInflammation03 medical and health sciences0302 clinical medicineCell Line TumorPancreatic cancerGeneticsmedicineHumanseducationChemotherapeutic drugMolecular BiologySignal transduction inhibitorAgededucation.field_of_studybusiness.industryCell CycleAutophagyCancerPDACDNA Neoplasmmedicine.diseaseGene Expression Regulation NeoplasticPancreatic Neoplasms030104 developmental biologyApoptosis030220 oncology & carcinogenesisCancer cellCancer researchMolecular MedicineChemotherapeutic drugsmedicine.symptombusinessDNA DamageSignal Transduction
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PD-1, PD-L1, and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: A expression patterns and clinical implications

2018

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), a variant of pancreatic ductal adenocarcinoma (PDAC), has a striking genetic similarity to PDAC but a significantly improved overall survival. We hypothesize that this difference could be due to the immune response to the tumor, and as such, we investigated the expression of PD-1, PD-L1, and CD163 in a series of UCOGC. To this aim, 27 pancreatic UCOGCs (11 pure and 16 PDAC-associated), 5 extrapancreatic tumors with osteoclast-like giant cells and 10 pancreatic anaplastic carcinomas were immunostained using antibodies against PD-1, PD-L1, and CD163. In pancreatic UCOGCs, PD-L1 was expressed in neoplastic cells of 17 (63%) o…

Male0301 basic medicineIndianaProgrammed Cell Death 1 ReceptorOsteoclast; PDAC; Pancreatic Cancer; Tumor-Associated Macrophages; UCOGCOsteoclastsGiant CellsB7-H1 Antigen0302 clinical medicineTumor-Associated MacrophagesTumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14]LymphocytesAged 80 and overbiologyTumor-associated macrophagesCell DifferentiationMiddle AgedOsteoclast; Pancreatic cancer; PDAC; Tumor-associated macrophages; UCOGC; 2734ImmunohistochemistryEuropePhenotypemedicine.anatomical_structure030220 oncology & carcinogenesisOsteoclastFemaleAntibodyCarcinoma Pancreatic DuctalAdult2734Antigens Differentiation MyelomonocyticReceptors Cell SurfaceUCOGCPathology and Forensic MedicinePancreatic Cancer03 medical and health sciencesImmune systemAll institutes and research themes of the Radboud University Medical CenterAntigens CDOsteoclastPD-L1Pancreatic cancerBiomarkers TumormedicineHumansHistiocyteAgedNeoplasm StagingPDACHistiocytesPancreatic cancermedicine.diseasePancreatic Neoplasms030104 developmental biologyGiant cellCancer researchbiology.proteinCD163
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1,2,4-Oxadiazole Topsentin Analogs with Antiproliferative Activity against Pancreatic Cancer Cells, Targeting GSK3β Kinase.

2021

A new series of topsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,2,4- oxadiazole moiety, was efficiently synthesized. All derivatives were pre-screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. The five most potent compounds were further investigated in various pancreatic ductal adenocarcinoma (PDAC) cell lines, including SUIT-2, Capan-1, and Panc-1 cells, eliciting EC50 values in the micromolar and sub-micromolar range, associated with significant reduction of cell migration. These remarkable results might be explained by the effects of these new topsentin analogues on epithelial-to-mesenchy…

Models MolecularIndoles124-oxadiazole topsentin analogs; GSK3β kinase; inhibition of migration; PDAC antiproliferative activity; proapoptotic activityApoptosisDrug Screening Assays01 natural sciencesBiochemistrychemistry.chemical_compound124-oxadiazole topsentin analogs; GSK3β kinase; PDAC antiproliferative activity; inhibition of migration; proapoptotic activity; Antineoplastic Agents; Apoptosis; Cell Proliferation; Cell Survival; Dose-Response Relationship Drug; Drug Screening Assays Antitumor; Glycogen Synthase Kinase 3 beta; Humans; Imidazoles; Indoles; Models Molecular; Molecular Structure; Oxadiazoles; Pancreatic Neoplasms; Protein Kinase Inhibitors; Structure-Activity Relationship; Tumor Cells CulturedModelsAnnexinDrug DiscoveryTumor Cells CulturedGSK3β kinaseGeneral Pharmacology Toxicology and Pharmaceutics4-oxadiazole topsentin analogsOxadiazolesCulturedMolecular StructureChemistryKinaseImidazolesCell migrationTumor Cellsinhibition of migrationMolecular MedicineDrugIntracellularPDAC antiproliferative activityproapoptotic activityCell Survival12Antineoplastic AgentsDose-Response RelationshipStructure-Activity RelationshipPancreatic cancermedicineHumansPropidium iodideProtein Kinase InhibitorsCell ProliferationPharmacologyGlycogen Synthase Kinase 3 betaDose-Response Relationship Drug010405 organic chemistryOrganic ChemistryMolecularAntitumormedicine.diseaseSettore CHIM/08 - Chimica FarmaceuticaMolecular biology0104 chemical sciencesPancreatic Neoplasms010404 medicinal & biomolecular chemistryApoptosisCell cultureDrug Screening Assays Antitumor124-oxadiazole topsentin analogChemMedChem
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Effects of the MDM2 inhibitor Nutlin-3a on sensitivity of pancreatic cancer cells to berberine and modified berberines in the presence and absence of…

2021

Abstract Approaches to improve pancreatic cancer therapy are essential as this disease has a very bleak outcome. Approximately 80% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). A key regulatory gene frequently mutated (∼75%) in PDAC is the TP53 tumor suppressor gene which controls the transcription of multiple genes involved in cell cycle progression, apoptosis, cancer progression and other growth regulatory processes. The mouse double minute 2 homolog (MDM2) gene product is a nuclear-localized E3 ubiquitin ligase and negatively regulates the TP53 protein which results in its proteasomal degradation. Various MDM2 inhibitors have been isolated and examined in clinical t…

Nutlin-3aCancer ResearchBerberineendocrine system diseasesTumor suppressor geneNAX compoundsApoptosisPiperazinesTargeted therapyGene productCell Line TumorPancreatic cancerGeneticsmedicineHumansTP53neoplasmsMolecular BiologyRegulator geneNAX compundsbiologyChemistryImidazolesPDACCancerProto-Oncogene Proteins c-mdm2PDCAmedicine.diseaseUbiquitin ligasePancreatic NeoplasmsCell culturebiology.proteinCancer researchNAX compoundMolecular MedicineMdm2Tumor Suppressor Protein p53Signal TransductionAdvances in Biological Regulation
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Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal a…

2017

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the…

PDAC variants; Undifferentiated carcinoma with osteoclast-like giant cells; whole exome sequencingAged 80 and overMaleendocrine system diseasesCarcinomaUndifferentiated carcinoma with osteoclast-like giant cellsundifferentiated carcinoma with osteoclast-like giant cellOsteoclastsMiddle AgedImmunohistochemistrydigestive system diseasesArticleNeoplasm Proteinswhole exome sequencingPDAC variants; undifferentiated carcinoma with osteoclast-like giant cells; whole exome sequencing; Aged; Aged 80 and over; Carcinoma Pancreatic Ductal; Exome; Female; Humans; Immunohistochemistry; Male; Middle Aged; Mutation; Neoplasm Proteins; Osteoclasts; Pancreatic NeoplasmsPancreatic NeoplasmsPDAC variantsPancreatic DuctalMutation80 and overHumansExomeFemaleAgedCarcinoma Pancreatic Ductal
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Extranodal extension in N1-adenocarcinoma of the pancreas and papilla of Vater: A systematic review and meta-analysis of its prognostic significance

2016

The aim of the study was to investigate the prognostic role of extranodal extension (ENE) of lymph node metastasis in adenocarcinoma of the pancreas (PDAC) and papilla [cancer of the papilla of Vater (CPV)]. A PubMed and SCOPUS search from database inception until 5 January 2015 without language restrictions was conducted. Eligible were prospective studies reporting data on prognostic parameters in individuals with PDAC and/or CPV, comparing participants with the presence of ENE (ENE +) with those with intranodal extension (ENE). Data were summarized using risk ratios for number of deaths/recurrences and hazard ratios for time-dependent risk related to ENE+, adjusted for potential confounde…

Time FactorsPapillaPapillary carcinomaGastroenterologyextranodal extension pancreatic adenocarcinoma papilla papillary carcinoma prognosislymph node metastasis adenocarcinoma of the pancreas (PDAC) papilla [cancer of the papilla of Vater (CPV)] extranodal extension (ENE)0302 clinical medicineRisk FactorsOdds RatioProspective cohort studylymph node metastasisHazard ratioAmpulla of VaterGastroenterologyPrognosisextranodal extension (ENE)medicine.anatomical_structureTreatment Outcome030220 oncology & carcinogenesisLymphatic Metastasisadenocarcinoma of the pancreas (PDAC)Disease ProgressionAdenocarcinoma030211 gastroenterology & hepatologymedicine.medical_specialtyAmpulla of VaterCommon Bile Duct NeoplasmsAdenocarcinomapapilla [cancer of the papilla of Vater (CPV)]Disease-Free Survival03 medical and health sciencesExtranodal extension; Pancreatic adenocarcinoma; Papilla; Papillary carcinoma; Prognosis; Gastroenterology; HepatologyPredictive Value of TestsInternal medicineExtranodal extensionmedicineHumansHepatologybusiness.industryOdds ratiomedicine.diseaseConfidence intervalSurgeryMajor duodenal papillaPancreatic NeoplasmsRelative riskLymph NodesNeoplasm Recurrence LocalbusinessPancreatic adenocarcinoma
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Malignant epithelial/exocrine tumors of the pancreas

2020

Summary Pancreatic malignant exocrine tumors represent the most important cause of cancer-related death for pancreatic neoplasms. The most common tumor type in this category is represented by pancreatic ductal adenocarcinoma (PDAC), an ill defined, stroma-rich, scirrhous neoplasm with glandular differentiation. Here we present the relevant characteristics of the most important PDAC variants, namely adenosquamous carcinoma, colloid carcinoma, undifferentiated carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, signet ring carcinoma, medullary carcinoma and hepatoid carcinoma. The other categories of malignant exocrine tumors, characterized by fleshy, stroma-poor, circumsc…

acinarPathologymedicine.medical_specialtyAdenosquamous carcinomapancreatic cancerPancreatoblastomapancreatic ductal adenocarcinomaReviewAdenocarcinomaGlandular DifferentiationPathology and Forensic MedicinePancreatic cancersolid pseudopapillary.medicineCarcinomaNeoplasmHumansacinar; pancreatic cancer; pancreatic ductal adenocarcinoma; PDAC; solid pseudopapillaryPancreasbusiness.industryPDACPDAC; acinar; pancreatic cancer; pancreatic ductal adenocarcinoma; solid pseudopapillarymedicine.diseasePancreas ExocrinePancreatic Neoplasmssolid pseudopapillarymedicine.anatomical_structureMedullary carcinomaPancreasbusinessCarcinoma Pancreatic Ductal
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Structural Manipulations of Marine Natural Products Inspire a New Library of 3-Amino-1,2,4-Triazine PDK Inhibitors Endowed with Antitumor Activity in…

2023

Pancreatic ductal adenocarcinoma (PDAC) is one of the main aggressive types of cancer, characterized by late prognosis and drug resistance. Among the main factors sustaining PDAC progression, the alteration of cell metabolism has emerged to have a key role in PDAC cell proliferation, invasion, and resistance to standard chemotherapeutic agents. Taking into account all these factors and the urgency in evaluating novel options to treat PDAC, in the present work we reported the synthesis of a new series of indolyl-7-azaindolyl triazine compounds inspired by marine bis-indolyl alkaloids. We first assessed the ability of the new triazine compounds to inhibit the enzymatic activity of pyruvate de…

nortopsentin analoguespancreatic ductal adenocarcinoma (PDAC); nortopsentin analogues; antitumor activity; pyruvate dehydrogenase kinases (PDKs); cytotoxic activity; metabolic alterations; ligand-based homology modeling; KRASDrug Discoveryligand-based homology modelingKRASPharmaceutical Scienceantitumor activitymetabolic alterationspancreatic ductal adenocarcinoma (PDAC)Pharmacology Toxicology and Pharmaceutics (miscellaneous)cytotoxic activitypyruvate dehydrogenase kinases (PDKs)
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