scholarly journals Polymer coated gold nanoshells for combinational photochemotherapy of pancreatic cancer with gemcitabine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mina Emamzadeh ◽  
George Pasparakis
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Weight ◽  
Parent Drug ◽  
Gold Nanoshells ◽  
Dismal Prognosis ◽  
Therapeutic Outcomes ◽  
Methacrylate Polymers ◽  
Interesting Class ◽  
Poly Ethylene

AbstractPancreatic cancer is one of the most lethal malignancies with limited therapeutic options and dismal prognosis. Gemcitabine is the front-line drug against pancreatic cancer however with limited improvement of therapeutic outcomes. In this study we envisaged the integration of GEM with gold nanoshells which constitute an interesting class of nanomaterials with excellent photothermal conversion properties. Nanoshells were coated with thiol-capped poly(ethylene glycol) methacrylate polymers of different molecular weight via Au–S attachment. It was found that the molecular weight of the polymers affects the in vitro performance of the formulations; more importantly we demonstrate that the EC50 of nanoshell loaded GEM can be suppressed but fully restored and even improved upon laser irradiation. Our proposed nanoformulations outperformed the cytotoxicity of the parent drug and showed confined synergism under the tested in vitro conditions.

A translational effort to identify prognostic and predictive biomarkers in pancreatic cancer among RBM3-regulated genes.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 305-305
Author(s):  
Sofie Olsson Hau ◽  
Emelie Karnevi ◽  
Sebastian Lundgren ◽  
Bo Li ◽  
Seodhna Lynch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Protein Expression ◽  
Rna Binding ◽  
Predictive Biomarkers ◽  
Gene Set Enrichment Analysis ◽  
Binding Motif ◽  
Potential Utility ◽  
Dismal Prognosis ◽  
Response To Chemotherapy

305 Background: Pancreatic cancer has a dismal prognosis and clinical protocols are still lacking predictive biomarkers. RNA-binding motif protein 3 (RBM3) has emerged as a promising biomarker in several solid cancers, including pancreatic cancer. High RBM3 expression in human tumors has been associated with good response to chemotherapy, as well as to confer increased chemosensitivity in vitro. The aim of this study was to identify RBM3-regulated genes in pancreatic cells in vitro, and further interrogate their potential utility as prognostic and predictive biomarkers in a translational setting. Methods: Next generation RNA-sequencing was applied to compare gene expression between MIAPaCa-2 cells with siRNA-downregulated RBM3 and control cells. Single genes with the strongest association to RBM3 were further selected by gene set enrichment analysis, and their prognostic value in pancreatic cancer was examined in The Cancer Genome Atlas (TCGA). The most promising biomarker candidates with well-validated antibodies were then analyzed by immunohistochemistry in tissue microarrays with tumors from a consecutive, retrospective cohort of 175 patients with periampullary and pancreatic adenocarcinoma. Results: MIAPaCa-2 cells with downregulated RBM3 displayed 21 differentially expressed genes (p < 0.01). One of the top downregulated genes was PDS cohesion associated factor A (PDS5A) encoding a protein involved in sister chromatid cohesion. PDS5A protein expression was reduced in siRBM3-treated MIAPaCa-2 cells compared to control cells. High PDS5A mRNA expression was significantly associated with a reduced survival in pancreatic cancer in the TCGA (n = 176, p = 0.026). High PDS5A protein expression in the separate cohort was significantly associated with a poor prognosis but predictive of improved response to adjuvant chemotherapy in KRAS-mutated, but not wild-type, pancreatobiliary-type tumors (p for interaction = 0.043). Conclusions: Here, we provide the first report of the expression of PDS5A in pancreatic and periampullary cancer, suggesting its potential utility as a prognostic and predictive biomarker. Further studies to unravel the underlying mechanisms are encouraged.

scholarly journals The Utility of a Novel Blood Based Biomarker in the Diagnosis of Pancreatic Cancer

2021 ◽  
Author(s):  
◽  
Lucy E. Nichols
Keyword(s):  
Pancreatic Cancer ◽  
Dna Damage ◽  
Human Peripheral Blood ◽  
Micronucleus Assay ◽  
Clinical Markers ◽  
Peripheral Blood Mononuclear ◽  
Markers Of Inflammation ◽  
Dismal Prognosis ◽  
Mutation Assay

Pancreatic cancer maintains one of the worst prognoses of all malignancies. Fewer than 1% of patients survive 10-years post-diagnosis. It is an aggressive disease with as many as 80% of patients diagnosed in the most advanced stages of disease. This severely limits treatment options, contributing to the dismal prognosis. Diagnosis remains a challenge. Often, imaging alone cannot differentiate between benign or malignant disease. Blood-based biomarker CA19-9 cannot be relied upon since it is a modified Lewis antigen so 5-10% of the population do not express it. Tissue biopsies remain the gold-standard for final confirmed diagnoses, yet collection of pancreatic biopsies is invasive, time and resource intensive and have a range of risks associated. Blood-based biomarkers offer a less invasive, cheaper, and more accessible alternative to more traditional diagnostic techniques. Here, we explored the use of novel DNA mutation assay, the human erythrocyte PIG-A assay, as a blood-based biomarker to determine whether it had any potential in diagnosing pancreatic cancer. An elevated frequency of PIG-A mutant erythrocytes was observed within pancreatic cancer patients in comparison to controls of healthy donors and a benign pancreatic disease cohort. Furthermore, the more well-established human peripheral blood mononuclear cell cytokinesis block micronucleus assay provided a secondary measure of DNA damage. An elevation was also viewed in this assay in malignant donors. Both assays were additionally explored within an in vitro setting, modelling the induction of DNA damage by known risk factors for pancreatic cancer. Given the complexity of pancreatic cancer diagnosis, a panel of biomarkers was explored, combining clinical markers of inflammation with our two DNA-based biomarkers and clinically approved CA19-9. Combination of the novel PIG-A mutation assay and CA19-9 blood-test appeared the most suitable panel of biomarkers for future exploration.

Evaluation of Acid-Treated Hyaluronic Acid-Based Hydrogelation

2007 ◽  
Vol 342-343 ◽  
pp. 745-748
Author(s):  
Mi Sook Kim ◽  
Yoon Jeong Choi ◽  
Gun Woo Kim ◽  
In Sup Noh ◽  
Yong Doo Park ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
Gel Permeation Chromatography ◽  
Biological Properties ◽  
Cellular Interactions ◽  
Molecular Weights ◽  
Chemical Structures ◽  
Poly Ethylene Oxide ◽  
Poly Ethylene

Though hyaluronic acid (HA)-based hydrogel has drawn great attention in biomedical society, it’s long molecular weights sometimes have been problematic due to its difficulty in handling. After reduction of its high molecular weight into smaller sizes with various concentrations of hydrogen chloride solutions, its chemical and biological properties have been examined by changes in viscosity, FTIR spectroscopy and gel permeation chromatography as well as cellular interactions. While FTIR analysis indicated maintenance of its original chemical structures, its viscosity has been remarkably reduced and its extent was dependent upon the employment of acid concentrations. After controlling its molecular weight to approximately 100 kDa and coupling of aminopropymethacrylate to the treated HA, we evaluated in vitro cellular interactions and cell proliferations of the HA-poly(ethylene oxide) (PEO) hydrogel.

Relevance of polymer molecular weight to the in vitro/in vivo performances of ocular inserts based on poly(ethylene oxide)

2001 ◽  
Vol 220 (1-2) ◽  
pp. 169-177 ◽  
Author(s):  
G Di Colo ◽  
S Burgalassi ◽  
P Chetoni ◽  
M.P Fiaschi ◽  
Y Zambito ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Ethylene Oxide ◽  
Polymer Molecular Weight ◽  
Poly Ethylene Oxide ◽  
Poly Ethylene

scholarly journals LINC00261 Is Differentially Expressed in Pancreatic Cancer Subtypes and Regulates a Pro-Epithelial Cell Identity

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1227 ◽  
Author(s):  
Agnes Dorn ◽  
Markus Glaß ◽  
Carolin T. Neu ◽  
Beate Heydel ◽  
Stefan Hüttelmaier ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Transforming Growth Factor ◽  
Human Cancer ◽  
Expression Patterns ◽  
Transcriptional Analysis ◽  
Mesenchymal Transition ◽  
Cancer Subtypes ◽  
Dismal Prognosis ◽  
Non Coding Rnas

Pancreatic adenocarcinoma (PDAC) is one of the major causes of cancer-associated deaths worldwide, with a dismal prognosis that has not significantly changed over the last decades. Transcriptional analysis has provided valuable insights into pancreatic tumorigenesis. Specifically, pancreatic cancer subtypes were identified, characterized by specific mutations and gene expression changes associated with differences in patient survival. In addition to differentially regulated mRNAs, non-coding RNAs, including long non-coding RNAs (lncRNAs), were shown to have subtype-specific expression patterns. Hence, we aimed to characterize prognostic lncRNAs with deregulated expression in the squamous subtype of PDAC, which has the worst prognosis. Extensive in silico analyses followed by in vitro experiments identified long intergenic non-coding RNA 261 (LINC00261) as a downregulated lncRNA in the squamous subtype of PDAC, which is generally associated with transforming growth factor β (TGFβ) signaling in human cancer cells. Its genomic neighbor, the transcription factor forkhead box protein A2 (FOXA2), regulated LINC00261 expression by direct binding of the LINC00261 promoter. CRISPR-mediated knockdown and promoter knockout validated the importance of LINC00261 in TGFβ-mediated epithelial–mesenchymal transition (EMT) and established the epithelial marker E-cadherin, an important cell adhesion protein, as a downstream target of LINC00261. Consequently, depletion of LINC00261 enhanced motility and invasiveness of PANC-1 cells in vitro. Altogether, our data suggest that LINC00261 is an important tumor-suppressive lncRNA in PDAC that is involved in maintaining a pro-epithelial state associated with favorable disease outcome.

scholarly journals Differently PEGylated Polymer Nanoparticles for Pancreatic Cancer Delivery: Using a Novel Near-Infrared Emissive and Biodegradable Polymer as the Fluorescence Tracer

2021 ◽  
Vol 9 ◽  
Author(s):  
Huazhong Cai ◽  
Yanxia Chen ◽  
Liusheng Xu ◽  
Yingping Zou ◽  
Xiaoliang Zhou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Near Infrared ◽  
Hydrophobic Interactions ◽  
Polymeric Nanoparticles ◽  
Fluorescent Nanoparticles ◽  
Pegylated Nanoparticles ◽  
Poly Ethylene ◽  
Tumor Accumulation

In this study, a chemically synthetic polymer, benzo[1,2-b:4,5-b′]difuran(BDF)-based donor–acceptor copolymer PBDFDTBO, was individually coated by amphiphilic poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol) (DSPE-PEG or PEG-DSPE), to form stably fluorescent nanoparticles in the near-infrared (NIR) window. The physicochemical properties of the synthesized nanoparticles were characterized and compared, including their size, surface charge, and morphology. In addition, in vitro studies were also performed using two pancreatic cancer cell lines, assessing the cell viability of the PBDFDTBO-included PEGylated nanoparticles formulations. Moreover, in vivo studies were also conducted, using subcutaneous murine cancer models to investigate the polymeric nanoparticles’ circulation time, tumor accumulation, and preferred organ biodistribution. The overall results demonstrated that even with the same PEGylated surface, the hydrophobic composition anchored on the encapsulated PBDFDTBO core strongly affected the biodistribution and tumor accumulation of the nanoparticles, to a degree possibly determined by the hydrophobic interactions between the hydrophobic segment of amphiphilic polymers (DSPE or PCL moiety) and the enwrapped PBDFDTBO. Both PEGylated nanoparticles were compared to obtain an optimized coating strategy for a desired biological feature in pancreatic cancer delivery.

The Structure of Radiation Cross-Linked Poly (ethylene oxide) Gels

1971 ◽  
Vol 29 ◽  
pp. 76-77
Author(s):  
C. E. Cluthe ◽  
G. G. Cocks
Keyword(s):  
Molecular Weight ◽  
Ethylene Oxide ◽  
Parallel Plate ◽  
Average Molecular Weight ◽  
Radical Reaction ◽  
Free Radical Reaction ◽  
Nitrogen Gas ◽  
Poly Ethylene Oxide ◽  
Poly Ethylene ◽  
Initial Viscosity

Aqueous solutions of a 1 weight-per cent poly (ethylene oxide) (PEO) were degassed under vacuum, transferred to a parallel plate viscometer under a nitrogen gas blanket, and exposed to Co60 gamma radiation. The Co60 source was rated at 4000 curies, and the dose ratewas 3.8x105 rads/hr. The poly (ethylene oxide) employed in the irradiations had an initial viscosity average molecular weight of 2.1 x 106.The solutions were gelled by a free radical reaction with dosages ranging from 5x104 rads to 4.8x106 rads.

Dermatan Sulfate and LMW Heparin Enhance the Anticoagulant Action of Activated Protein C

1999 ◽  
Vol 82 (11) ◽  
pp. 1462-1468 ◽  
Author(s):  
José Fernández ◽  
Jari Petäjä ◽  
John Griffin
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Protein C ◽  
Dermatan Sulfate ◽  
Anticoagulant Activity ◽  
Activated Protein C ◽  
Factor V ◽  
Factor Va ◽  
Anticoagulant Action

SummaryUnfractionated heparin potentiates the anticoagulant action of activated protein C (APC) through several mechanisms, including the recently described enhancement of proteolytic inactivation of factor V. Possible anticoagulant synergism between APC and physiologic glycosaminoglycans, pharmacologic low molecular weight heparins (LMWHs), and other heparin derivatives was studied. Dermatan sulfate showed potent APC-enhancing effect. Commercial LMWHs showed differing abilities to promote APC activity, and the molecular weight of LMWHs correlated with enhancement of APC activity. Degree of sulfation of the glycosaminoglycans influenced APC enhancement. However, because dextran sulfates did not potentiate APC action, the presence of sulfate groups per se on a polysaccharide is not sufficient for APC enhancement. As previously for unfractionated heparin, APC anticoagulant activity was enhanced by glycosaminoglycans when factor V but not factor Va was the substrate. Thus, dermatan sulfate and LMWHs exhibit APC enhancing activity in vitro that could be of physiologic and pharmacologic significance.

Sign in / Sign up

Export Citation Format

Share Document