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Three-Dimensional (3d) In Vitro Cell Culture Protocols To Enhance Glioblastoma Research, Janith Wanigasekara, Lara Carroll, Patrick J. Cullen, Brijesh K. Tiwari, James Curtin

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Three-dimensional (3D) cell culture models can help bridge the gap between in vitro cell cultures and in vivo responses by more accurately simulating the natural in vivo environment, shape, tissue stiffness, stressors, gradients and cellular response while avoiding the costs and ethical concerns associated with animal models. The inclusion of the third dimension in 3D cell culture influences the spatial organization of cell surface receptors that interact with other cells and imposes physical restrictions on cells in compared to Two-dimensional (2D) cell cultures. Spheroids’ distinctive cyto-architecture mimics in vivo cellular structure, gene expression, metabolism, proliferation, oxygenation, nutrition absorption, waste excretion, …

Taste And Smell Abnormalities In Advanced Cancer: Negative Impact On Subjective Food Intake, Aidan O'Donoghue, Michelle Barrett, Pauline Uí Dhuibhir Pauline Uí Dhuibhir, Aileen Kennedy, Norma O'Leary, Declan Walshe

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Background: Taste and smell abnormalities (TSAs) are present in all cancer stages and may contribute to malnutrition. Despite this, they are rarely screened for. This study examined the prevalence and characteristics of TSAs and their influence on subjective food intake in advanced cancer. Methods: Consecutive patients with advanced cancer were recruited. A modified Taste and Smell Survey assessed subjective TSAs. Objective TSAs were assessed with validated taste strips and "Sniffin Sticks." A six-item food intake questionnaire identified any effect TSAs had on food preferences/aversions. Nutrition status was evaluated with the abridged Patient-Generated Subjective Global Assessment. Results: All 30 participants had …

Structural And Solution Speciation Studies On Selected [Cu(Nn)(Oo)] Complexes And An Investigation Of Their Biomimetic Activity, Ros Generation And Their Cytotoxicity In Normoxic, Hypoxic And Anoxic Environments In Mcf-7 Breast Cancer-Derived Cells, Hollie Jenkins

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Reactive oxygen species(ROS) generation with subsequent DNA damage is one of the principle mechanisms of action assigned to copper-based anticancer complexes. The efficacy of this type of chemotherapeutic may be reduced in the low oxygen environment of tumours. In this study the cytotoxicity of three complexes, [Cu(dips)(phen)] (1), [Cu(ph)(phen)]·2H2O (2) and [Cu(ph)(bpy)]·H2O (3) (disp: 3,5-diisopropylsalicylate, phen: 1,10- phenanthroline, ph: phthalate, bpy: 2,2′-bipyridyl) were assessed for anticancer activity in the breast-cancer derived MCF-7 line under normoxic, hypoxic and anoxic conditions. In an immortalised keratinocyte HaCaT cell line, the cytotoxicity of complexes 2 and 3 was significantly reduced under both normoxic and …

Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara

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Ultrasound is a sound wave with frequencies ranging between 20 kHz and 20 MHz. Ultrasound is able to temporarily and repeatedly open the BBB safely and enhance chemotherapeutic delivery without adverse effects. This novel technique in drug delivery benefits from the powerful ability of ultrasound to produce cavitation activity. Cavitation is the generation and activity of gas-filled bubbles in a medium exposed to ultrasound. As the pressure wave passes through the media, gas bubbles expand at low pressure and contract at high pressure. This leads to oscillation which produces a circulating fluid flow known as microstreaming around the bubble with …

Synergistic Anticancer Response Of Curcumin And Piperine Loaded Lignin-G-P (Nipam-Co-Dmaema) Gold Nanogels Against Glioblastoma Multiforme, Xinyi Zhao, Bilal Javad, Daxing Cui, James Curtin, Furong Tian

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Glioblastoma multiforme (GBM) is the most aggressive and commonly diag- 11 nosed brain cancer and presents a strong resistance to routine chemotherapeutic drugs. 12 The present study involves the synthesis of Lignin-g- p (NIPAM-co-DMAEMA) gold 13 nanogel, loaded with curcumin and piperine to treat GBM. The application has three 14 functions: (1) overcome the limitations of biodistribution, (2) enhance the toxicity of an- 15 ticancer drugs against GBM, (3) identify the uptake pathway. Atom transfer radical 16 polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with 17 the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and …

Enhanced Anticancer Response Of Curcumin- And Piperine-Loaded Lignin-G-P (Nipam-Co-Dmaema) Gold Nanogels Against U-251 Mg Glioblastoma Multiforme, Bilal Javed, Xinyi Zhao, Daxiang Cui, James Curtin, Furong Tian

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Glioblastoma multiforme (GBM) is the most aggressive and commonly diagnosed brain cancer and is highly resistant to routine chemotherapeutic drugs. The present study involves the synthesis of Lignin-g-p (NIPAM-co-DMAEMA) gold nanogel, loaded with curcumin and piperine, to treat GBM. The ongoing study has the application potential to (1) overcome the limitations of drugs biodistribution, (2) enhance the toxicity of anticancer drugs against GBM, and (3) identify the drugs uptake pathway. Atom transfer radical polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and morphological analysis confirmed that the …

Converging Technologies: Targeting The Hallmarks Of Cancer Using Ultrasound And Microbubbles, Janith Wanigasekara, Andressa Maria Aguiar De Carvalho, Patrick J. Cullen, Brijesh Tiwari, James F. Curtin

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Various complex biological effects occur when ultrasonic compression waves travel through biological material. The myriad of biological outcomes instigated by ultrasound are evident when viewed through the lens of the hallmarks of cancer. Herein, we summarise the therapeutic potential of ultrasound, enhanced by microbubbles, for the treatment of cancer.

Cold Atmospheric Plasma Induces Silver Nanoparticle Uptake, Oxidative Dissolution And Enhanced Cytotoxicity In Glioblastoma Multiforme Cells, Eline Manaloto, Aoife Gowen, Anna Lesniak, Zhonglei He, Alan Casey, Patrick J. Cullen, James Curtin

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Silver nanoparticles (AgNP) emerged as a promising reagent for cancer therapy with oxidative stress implicated in the toxicity. Meanwhile, studies reported cold atmospheric plasma (CAP) generation of reactive oxygen and nitrogen species has selectivity towards cancer cells. Gold nanoparticles display synergistic cytotoxicity when combined with CAP against cancer cells but there is a paucity of information using AgNP, prompting to investigate the combined effects of CAP using dielectric barrier discharge system (voltage of 75 kV, current is 62.5 mA, duty cycle of 7.5kVA and input frequency of 50–60Hz) and 10 nm PVA-coated AgNP using U373MG Glioblastoma Multiforme cells. Cytotoxicity in …

The Abundance Of Akkermansia Muciniphila And Its Relationship With Sulphated Colonic Mucins In Health And Ulcerative Colitis, Helen Earley, Grainne Earley, Aine Balfe, J. Calvin Coffey, Desmond C. Winter, Ronan O'Connell

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Akkermansia muciniphila utilises colonic mucin as its substrate. Abundance is reduced in ulcerative colitis (UC), as is the relative proportion of sulphated mucin in the mucus gel layer (MGL). It is unknown if these phenomena are related, however reduced sulphated mucins could contribute to reduced abundance, owing to a lack of substrate. The aim of this study was to quantify A. muciniphila within the MGL and to relate these findings with markers of inflammation and the relative proportion of sulphomucin present. Colonic biopsies and mucus brushings were obtained from 20 patients with active UC (AC), 14 with quiescent UC (QUC) …

Subjective And Objective Assessment Of Taste And Smell Sensation In Advanced Cancer, Niamh Mcgettigan, Pauline Uí Dhuibhir, Michelle Barrett, Jessica Sui, Lucy Balding, Stephen Higgins, Norma O'Leary, Aileen Kennedy, Declan Walsh

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Context: Taste and smell abnormalities (TSA) occur throughout the cancer trajectory regardless of cancer primary site and contribute to cancer-associated malnutrition. TSA etiology is poorly understood. Tumor-related inflammation is a possible cause. Objective: This study examined the prevalence, characteristics, and severity of TSA in advanced cancer and explored the relationship between TSA and nutritional status. No previous study combined subjective and objective measures for both taste and smell assessment in this population. Method: Consecutive advanced cancer hospice patients were recruited. A modified version of the “Taste and Smell Survey” assessed subjective TSA. Validated taste strips and “Sniffin’ …

Hydrogen Peroxide And Beyond - The Potential Of High-Voltage Plasma Activated Liquids Against Cancerous Cells, Daniela Boehm, James Curtin, Patrick Cullen, Paula Bourke

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Abstract: The use of plasma-activated liquids such as PBS, medium or simply plasma-activated water (PAW) has been receiving increasing attention for applications in cancer treatments. Amongst the reactive species contained in these solutions, hydrogen peroxide appears to play a pivotal role in causing cytotoxic effects. While H2O2 concentrations can be correlated with reduced cell viability and growth and used as an indicator of the potential efficacy of a plasma-activated water, comparisons to standard H2O2 kill curves demonstrate a potency in PAW which exceeds H2O2 associated toxicity, indicating that other plasma-generated species play an important role. Using a high-voltage dielectric barrier …

Carcinogenesis In Prostate Cancer: The Role Of Long Non-Coding Rnas, John Aird, Anne-Marie Baird, Marvin C.J Lim, Ray Mcdermott, Stephen P. Finn, Steven G. Gray

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LncRNAs appear to play a considerable role in tumourigenesis through regulating key processes in cancer cells such as proliferative signalling, replicative immortality, invasion and metastasis, evasion of growth suppressors, induction of angiogenesis and resistance to apoptosis. LncRNAs have been reported to play a role in prostate cancer, particularly in regulating the androgen receptor signalling pathway. In this review article, we summarise the role of 34 lncRNAs in prostate cancer with a particular focus on their role in the androgen receptor signalling pathway and the epithelial to mesenchymal transition pathway.

Off-Target Effects Of Drugs That Disrupt Human Mitochondrial Dna Maintenance., Matthew J Young

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Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs used to treat human immunodeficiency virus (HIV) the cause of acquired immunodeficiency syndrome. Development of severe mitochondrial toxicity has been well documented in patients infected with HIV and administered NRTIs. In vitro biochemical experiments have demonstrated that the replicative mitochondrial DNA (mtDNA) polymerase gamma, Polg, is a sensitive target for inhibition by metabolically active forms of NRTIs, nucleotide reverse transcriptase inhibitors (NtRTIs). Once incorporated into newly synthesized daughter strands NtRTIs block further DNA polymerization reactions. Human cell culture and animal studies have demonstrated that cell lines and mice exposed to NRTIs …

The Glycosyltransferase Gnt-Iii Activates Notch Signaling And Drives Stem Cell Expansion To Promote The Growth And Invasion Of Ovarian Cancer, Heba Allam, Blake P. Johnson, Mao Zhang, Zhongpeng Lu, Martin J. Cannon, Karen L. Abbott

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Glycosylation changes associated with cellular transformation can facilitate the growth and progression of tumors. Previously we discovered that the gene Mgat3 encoding the glycosyltransferase GnT-III is elevated in epithelial ovarian carcinomas (EOCs) and leads to the production of abnormal truncated N-linked glycan structures instead of the typical bisected forms. In this study, we are interested in discovering how these abnormal glycans impact the growth and progression of ovarian cancer. We have discovered using stable shRNA gene suppression that GnT-III expression controls the expansion of side-population cells, also known as cancer stem cells. More specifically, we found that GnT-III expression regulates …

Cancer Incidence In Ireland—The Possible Role Of Diet, Nutrition And Lifestyle, Daniel Mccartney, Declan Byrne, Marie Cantwell, Michael Turner

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Aim This observational ecological study aims to compare Ireland’s age-specific cancer incidence rates (ASRs) with equivalent European and global data and to highlight possible dietary, nutritional and lifestyle contributors to cancer in Ireland.

Subjects and methods Using the International Agency for Research on Cancer’s (IARC) GLOBOCAN database, Irish ASRs for all-site cancer and for "lifestyle-related" cancers such as those of the colo-rectum, oesophagus, breast, lung and prostate were compared with European and global incidence data. Irish dietary and nutrient intake data were reviewed and evaluated in the context of these cancer incidence data and in relation to the established dietary, …

The "Eyes" Have It?-Intra- And Inter-Observer Reproducibility Of The Pd-L1 Companion Diagnostic Assay, Steven G. Gray, Mark Wright, Stephen Finn

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No abstract available.

Homeostatic Signaling By Cell-Cell Junctions And Its Dysregulation During Cancer Progression., Yang Yu, Randolph C Elble

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The transition of sessile epithelial cells to a migratory, mesenchymal phenotype is essential for metazoan development and tissue repair, but this program is exploited by tumor cells in order to escape the confines of the primary organ site, evade immunosurveillance, and resist chemo-radiation. In addition, epithelial-to-mesenchymal transition (EMT) confers stem-like properties that increase efficiency of colonization of distant organs. This review evaluates the role of cell-cell junctions in suppressing EMT and maintaining a quiescent epithelium. We discuss the conflicting data on junctional signaling in cancer and recent developments that resolve some of these conflicts. We focus on evidence from breast …

Non-Thermal Atmospheric Plasma Induces Ros-Independent Cell Death In U373mg Glioma Cells And Augments The Cytotoxicity Of Temozolomide, Gillian Conway, Alan Casey, Vladimir Milosavljevic, Yupeng Liu, Orla L. Howe, Patrick Cullen, James Curtin

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Non-thermal atmospheric plasma (NTAP) is an ionised gas produced under high voltage that can generate short-lived chemically active species and induce a cytotoxic insult in cancer cells. Cell-specific resistance to NTAP-mediated cytotoxicity has been reported in the literature. The aim of this study was to determine whether resistance against NTAP could be overcome using the human glioma cell line U373MG.

Methods:

Non-thermal atmospheric plasma was generated using a Dielectric Barrier Device (DBD) system with a maximum voltage output of 120 kV at 50 Hz. The viability of U373MG GBM cells and HeLa cervical carcinoma cells was determined using morphology, flow …

Parallel Profiles Of Inflammatory And Effector Memory T Cells In Visceral Fat And Liver Of Obesity-Associated Cancer Patients, Melissa Conroy, Karen Galvin, Suzanne Doyle, Maria Kavanagh, Ann-Marie Mongan, Aoife Cannon, Gillian Moore, John Reynolds, Joanne Lysaght

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In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease. We have previously identified that omentum is enriched with inflammatory cytokines, chemokines and T cells. Here, we compared the inflammatory profile of T cells in the omentum …

The Microenvironment Of Visceral Adipose Tissue And Liver Alter Natural Killer Cell Viability And Function, Melissa J. Conroy, Vivienne Fitzgerald, Suzanne Doyle, Shauna Channon, Zivile Useckaite, Niamh Gilmartin, Cliona O'Farrelly, Narayanasamy Ravi, John V. Reynolds, Joanne Lysaght

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The role of NK cells in visceral adipose tissue (VAT) and liver inflammation in obesity is not fully understood. This study investigated the frequency, cytokine expression, chemokine receptor, and cytotoxicity receptor profile of NK cells in the blood, omentum, and liver of patients with the obesity-associated cancer, oesophageal adenocarcinoma (OAC). The effect of chronically inflamed tissue microenvironments on NK cell viability and function was also examined. We identified significantly lower NK cell frequencies in the liver of OAC patients compared with healthy controls and within the omentum and liver of OAC patients compared with blood, whereas IL-10-producing populations were significantly …

Rnai-Based Glyconanoparticles Trigger Apoptotic Pathways For In Vitro And In Vivo Enhanced Cancer-Cell Killing, Joao Conde, Furong Tian, Yulan Hernandez, Chenchen Bao, Pedro Baptista, Daxiang Cui, Tobias Stoeger, Jesus M. De La Fuentec

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biotechnology and material science due to their amazing physical, chemical and biological properties. Here, siRNA GlycoNPs (AuNP@PEG@Glucose@siRNA) in comparison to PEGylated GlycoNPs (AuNP@PEG@Glucose) were applied in vitro to a luciferase-CMT/167 adenocarcinoma cancer cell line and in vivo via intratracheal instillation directly into the lung of B6 albino mice grafted with luciferase-CMT/167 adenocarcinoma cells. siRNA GlycoNPs but not PEGylated GlycoNPs induced the expression of pro-apoptotic proteins such as Fas/CD95 and caspases 3 and 9 in CMT/167 adenocarcinoma cells in a dose dependent manner, independent from the inflammatory response, evaluated by bronchoalveolar lavage cell counting. Moreover, in vivo pulmonary delivered siRNA GlycoNPs …

Building A Model Of Tumorigenesis: A Small Group Activity For A Cancer Biology/Cell Biology Course, Leslie Kate Wright

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The multistep nature of tumorigenesis is a foundational concept in the context of Cancer Biology. Many students do not appreciate the complex nature of cancer development nor do they understand how scientists are able to unravel the molecular pathways that lead to tumorigenesis. In this small group activity, students are presented with background information about the multistep nature of tumorigenesis and complete a priming activity that allows them to brainstorm and discuss experimental design. Students are then presented with data from the landmark manuscript, published in 1998 by Vogelstein et al., describing the first pathway of genetic alterations associated …

Current Advances In The Application Of Raman Spectroscopy For Molecular Diagnosis Of Cervical Cancer, Ines Martins Ramos, Alison Malkin, Fiona Lyng

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Raman spectroscopy provides a unique biochemical fingerprint capable of identifying and characterizing the structure of molecules, cells and tissues. In cervical cancer, it is acknowledged as a promising biochemical tool due to its ability to detect pre-malignancy and early malignancy stages. This review summarizes the key research in the area and the evidence compiled is very encouraging for ongoing and further research. In addition to the diagnostic potential, promising results for HPV detection and monitoring treatment response suggest more than just a diagnosis prospective. A greater body of evidence is however necessary before Raman spectroscopy is fully validated for clinical …

Long-Term Financial Burden Of Breast Cancer: Experiences Of A Diverse Cohort Of Survivors Identified Through Population-Based Registries, Reshma Jagsi, John A.E. Pottow, Kent A. Griffith, Cathy Bradley, Ann S. Hamilton, John Graff Rutgers University, Steven J. Katz, Sarah T. Hawley

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Purpose: To evaluate the financial experiences of a racially and ethnically diverse cohort of long-term breast cancer survivors (17% African American, 40% Latina) identified through population-based registries. Methods: Longitudinal study of women diagnosed with nonmetastatic breast cancer in 2005 to 2007 and reported to the SEER registries of metropolitan Los Angeles and Detroit. We surveyed 3,133 women approximately 9 months after diagnosis and 4 years later. Multivariable models evaluated correlates of self-reported decline in financial status attributed to breast cancer and of experiencing at least one type of privation (economically motivated treatment nonadherence and broader hardships related to medical expenses). …

Effect Of Substrate Choice And Tissue Type On Tissue Preparation For Spectral Histopathology By Raman Microspectroscopy, Hugh Byrne, Leanne M. Fullwood, Dave Griffiths, Katherine Ashton, Timothy Dawson, Robert W. Lea, Charles Davis, Franck Bonnier, Matthew J. Baker

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Raman spectroscopy is a non-destructive, non-invasive, rapid and economical technique which has the potential to be an excellent method for the diagnosis of cancer and understanding disease progression through retrospective studies of archived tissue samples. Historically, biobanks are generally comprised of formalin fixed paraffin preserved tissue and as a result these specimens are often used in spectroscopic research. Tissue in this state has to be dewaxed prior to Raman analysis to reduce paraffin contributions in the spectra. However, although the procedures are derived from histopathological clinical practice, the efficacy of the dewaxing procedures that are currently employed is questionable. Ineffective …

Malpractice Suits And Physician Apologies In Cancer Care, Eugene Chung, Jill R. Horwitz, John A.E. Pottow, Reshma Jagsi

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Conside the following case: The patient is a 44-year-old woman who presents for radiation treatment of an isolated locoregional recurrence of breat cancer in her chest wall, 3 years after undergoing masectomy. At the time of diagnosis, she had T2N2M0 disease, with four of 15 lymph nodes involved with tumor. She received a masectomy with negative margins and appropriate chemotherapy, but none of her physicians talked to her about postmasectomy radiation therapy, which would clearly have been indicated to reduce her risk of locoregional failure and would have been expected to improve her likelihood of survival. She asks the radiation …

Treg Depletion Inhibits Efficacy Of Cancer Immunotherapy: Implications For Clinical Trials., James Curtin, Marianela Candolfi, Tamer Fakhouri, Chunyan Liu, Anderson Alden, Matthew Edwards, Pedro Lowenstein, Maria Castro

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BACKGROUND: Regulatory T lymphocytes (Treg) infiltrate human glioblastoma (GBM); are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients. FINDINGS: Using a syngeneic intracrabial glioblastoma (GBM) mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs …