11 pages, 2951 KiB  
Review
Nanopulse Stimulation (NPS) Induces Tumor Ablation and Immunity in Orthotopic 4T1 Mouse Breast Cancer: A Review
by Stephen J. Beebe *, Brittany P. Lassiter and Siqi Guo
Frank Reidy Research Center for Bioelectrics, 4211 Monarch Ways, Suite 300, Norfolk, VA 23508, USA
Cancers 2018, 10(4), 97; https://doi.org/10.3390/cancers10040097 - 30 Mar 2018
Cited by 28 | Viewed by 6977
Abstract
Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic [...] Read more.
Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD). With lower electric fields, like those peripheral to the primary treatment zone, NPS can activate dendritic cells (DCs). The activation of DCs by dead/dying cells leads to increases in memory effector and central memory T-lymphocytes in the blood and spleen. NPS also eliminates immunosuppressive cells in the tumor microenvironment and blood. Finally, NPS treatment of 4T1 breast cancer exhibits an abscopal effect and largely prevents spontaneous metastases to distant organs. NPS with fast rise–fall times and pulse durations near the plasma membrane charging time constant, which exhibits transient, high-frequency components (1/time = Hz), induce responses from mitochondria, endoplasmic reticulum, and nucleus. Such effects may be responsible for release of danger-associated molecular patterns, including ATP, calreticulin, and high mobility group box 1 (HMBG1) from 4T1-Luc cells to induce immunogenic cell death (ICD). This likely leads to immunity and the vaccine-like response. In this way, NPS acts as a unique onco-immunotherapy providing distinct therapeutic advantages showing possible clinical utility for breast cancers as well as for other malignancies. Full article
(This article belongs to the Special Issue Electric Field Based Therapies for Cancer: A Selection of Papers from the 2nd World Congress on Electroporation)
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13 pages, 6518 KiB  
Article
Dissecting the Mutational Landscape of Cutaneous Melanoma: An Omic Analysis Based on Patients from Greece
by Georgia Kontogianni 1,2, Georgia Piroti 1, Ilias Maglogiannis 2, Aristotelis Chatziioannou 1,3,* and Olga Papadodima 1,*
1 Metabolic Engineering and Bioinformatics Group, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 11635 Athens, Greece
2 Department of Digital Systems, School of Information and Communication Technologies, University of Piraeus, 18534 Piraeus, Greece
3 e-NIOS Applications Private Company, 17671 Kallithea, Greece
Cancers 2018, 10(4), 96; https://doi.org/10.3390/cancers10040096 - 29 Mar 2018
Cited by 11 | Viewed by 5219
Abstract
Melanoma is a lethal type of skin cancer, unless it is diagnosed early. Formalin-fixed, paraffin-embedded (FFPE) tissue is a valuable source for molecular assays after diagnostic examination, but isolated nucleic acids often suffer from degradation. Here, for the first time, we examine primary [...] Read more.
Melanoma is a lethal type of skin cancer, unless it is diagnosed early. Formalin-fixed, paraffin-embedded (FFPE) tissue is a valuable source for molecular assays after diagnostic examination, but isolated nucleic acids often suffer from degradation. Here, for the first time, we examine primary melanomas from Greek patients, using whole exome sequencing, so as to derive their mutational profile. Application of a bioinformatic framework revealed a total of 10,030 somatic mutations. Regarding the genes containing putative protein-altering mutations, 73 were common in at least three patients. Sixty-five of these 73 top common genes have been previously identified in melanoma cases. Biological processes related to melanoma were affected by varied genes in each patient, suggesting differences in the components of a pathway possibly contributing to pathogenesis. We performed a multi-level analysis highlighting a short list of candidate genes with a probable causative role in melanoma. Full article
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19 pages, 18971 KiB  
Article
Differentiation Therapy Targeting the β-Catenin/CBP Interaction in Pancreatic Cancer
by Philipp Manegold 1,2,†, Keane K. Y. Lai 1,3,4,5,6,†, Yongfeng Wu 1,2, Jia-Ling Teo 1,2,4, Heinz-Josef Lenz 1,2,7, Yuri S. Genyk 8, Stephen J. Pandol 6,9, Kaijin Wu 1,2, David P. Lin 4, Yibu Chen 10, Cu Nguyen 1,2,4, Yi Zhao 1,2,7 and Michael Kahn 1,2,4,5,11,12,*
1 Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA
2 Center for Molecular Pathways and Drug Discovery, University of Southern California, Los Angeles, CA 90033, USA
3 Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA
4 Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
5 City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA
6 Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis, Department of Pathology, University of Southern California, Los Angeles, CA 90033, USA
7 Department of Medicine, University of Southern California, Los Angeles, CA 90033, USA
8 Department of Surgery, University of Southern California, Los Angeles, CA 90033, USA
9 Pancreatic Research Program, Cedars-Sinai Medical Center, Veterans Affairs Greater Los Angeles Healthcare System, and Department of Medicine, University of California, Los Angeles, CA 90048, USA
10 Health Sciences Libraries, University of Southern California, Los Angeles, CA 90033, USA
11 Department of Biochemistry and Molecular Medicine, University of Southern California, Los Angeles, CA 90033, USA
12 Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, CA 90033, USA
† These authors contributed equally to this work.
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Cancers 2018, 10(4), 95; https://doi.org/10.3390/cancers10040095 - 29 Mar 2018
Cited by 45 | Viewed by 7862
Abstract
Background: Although canonical Wnt signaling is known to promote tumorigenesis in pancreatic ductal adenocarcinoma (PDAC), a cancer driven principally by mutant K-Ras, the detailed molecular mechanisms by which the Wnt effector β-catenin regulates such tumorigenesis are largely unknown. We have previously demonstrated [...] Read more.
Background: Although canonical Wnt signaling is known to promote tumorigenesis in pancreatic ductal adenocarcinoma (PDAC), a cancer driven principally by mutant K-Ras, the detailed molecular mechanisms by which the Wnt effector β-catenin regulates such tumorigenesis are largely unknown. We have previously demonstrated that β-catenin’s differential usage of the Kat3 transcriptional coactivator cyclic AMP-response element binding protein-binding protein (CBP) over its highly homologous coactivator p300 increases self-renewal and suppresses differentiation in other types of cancer. Aim/methods: To investigate Wnt-mediated carcinogenesis in PDAC, we have used the specific small molecule CBP/β-catenin antagonist, ICG-001, which our lab identified and has extensively characterized, to examine its effects in human pancreatic cancer cells and in both an orthotopic mouse model and a human patient-derived xenograft (PDX) model of PDAC. Results/conclusion: We report for the first time that K-Ras activation increases the CBP/β-catenin interaction in pancreatic cancer; and that ICG-001 specific antagonism of the CBP/β-catenin interaction sensitizes pancreatic cancer cells and tumors to gemcitabine treatment. These effects were associated with increases in the expression of let-7a microRNA; suppression of K-Ras and survivin; and the elimination of drug-resistant cancer stem/tumor-initiating cells. Full article
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20 pages, 13761 KiB  
Review
The Hippo Pathway: Immunity and Cancer
by Zaid Taha †, Helena J. Janse van Rensburg † and Xiaolong Yang *
1 Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
† These authors contributed equally to this work.
Cancers 2018, 10(4), 94; https://doi.org/10.3390/cancers10040094 - 28 Mar 2018
Cited by 124 | Viewed by 18023
Abstract
Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway [...] Read more.
Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work. Full article
(This article belongs to the Special Issue Hippo Pathway in Cancer, towards Realization of the Hippo-Targeted Therapy)
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22 pages, 5147 KiB  
Review
The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas
by Ines Garces de los Fayos Alonso 1,2,3,†, Huan-Chang Liang 3,†, Suzanne D. Turner 4, Sabine Lagger 2,‡, Olaf Merkel 3,‡ and Lukas Kenner 1,2,3,*,‡
1 Ludwig Boltzmann Institute for Cancer Research, 1090 Vienna, Austria
2 Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria
3 Clinical Institute of Pathology, Medical University of Vienna, 1090 Vienna, Austria
4 Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB21QP, UK
† Co-first authors.
‡ Co-last authors.
Cancers 2018, 10(4), 93; https://doi.org/10.3390/cancers10040093 - 28 Mar 2018
Cited by 118 | Viewed by 14901
Abstract
The Activator Protein-1 (AP-1) transcription factor (TF) family, composed of a variety of members including c-JUN, c-FOS and ATF, is involved in mediating many biological processes such as proliferation, differentiation and cell death. Since their discovery, the role of AP-1 TFs in cancer [...] Read more.
The Activator Protein-1 (AP-1) transcription factor (TF) family, composed of a variety of members including c-JUN, c-FOS and ATF, is involved in mediating many biological processes such as proliferation, differentiation and cell death. Since their discovery, the role of AP-1 TFs in cancer development has been extensively analysed. Multiple in vitro and in vivo studies have highlighted the complexity of these TFs, mainly due to their cell-type specific homo- or hetero-dimerization resulting in diverse transcriptional response profiles. However, as a result of the increasing knowledge of the role of AP-1 TFs in disease, these TFs are being recognized as promising therapeutic targets for various malignancies. In this review, we focus on the impact of deregulated expression of AP-1 TFs in CD30-positive lymphomas including Classical Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma. Full article
(This article belongs to the Special Issue Advances in Our Understanding of ALK-Related Cancers: A Selection of Papers from the Joint Annual Meeting of the European Research Initiative for ALK-Related Malignancies (ERIA) and the European Union Marie Curie European Training Network ALKATRAS)
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12 pages, 2636 KiB  
Article
Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene
by Mario Monaco 1,†, Giuseppe Palma 2,†, Michela Vitiello 3, Anna Capiluongo 1, Barbara D’Andrea 4, Emilia Vuttariello 1, Antonio Luciano 2, Laura Cerchia 3, Gennaro Chiappetta 1, Claudio Arra 2, Alfredo Fusco 5 and Monica Fedele 3,*
1 Dipartimento di Ricerca Traslazionale a Supporto dei Percorsi Oncologici, S.C. Genomica Funzionale, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, 80131 Naples, Italy
2 S.S.D. Sperimentazione Animale, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, 80131 Naples, Italy
3 CNR—Institute of Experimental Endocrinology and Oncology (IEOS), 80131 Naples, Italy
4 Centro Medico Polispecialistico (CMO), 80100 Naples, Italy
5 Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy
† These authors contributed equally to this work.
Cancers 2018, 10(4), 92; https://doi.org/10.3390/cancers10040092 - 27 Mar 2018
Cited by 7 | Viewed by 3959
Abstract
POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is an emerging cancer-related gene that is downregulated in different human malignancies, including thyroid cancer, where its levels gradually decrease going from papillary thyroid carcinomas (PTC) to poorly differentiated and undifferentiated highly aggressive anaplastic carcinomas [...] Read more.
POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is an emerging cancer-related gene that is downregulated in different human malignancies, including thyroid cancer, where its levels gradually decrease going from papillary thyroid carcinomas (PTC) to poorly differentiated and undifferentiated highly aggressive anaplastic carcinomas (ATC). The restoration of PATZ1 expression in thyroid cancer cells reverted their malignant phenotype by inducing mesenchymal-to-epithelial transition, thus validating a tumor suppressor role for PATZ1 and suggesting its involvement in thyroid cancer progression. Here, we investigated the consequences of the homozygous and heterozygous loss of PATZ1 in the context of a mouse modeling of PTC, represented by mice carrying the RET/PTC1 oncogene under the thyroid specific control of the thyroglobulin promoter RET/PTC1 (RET/PTC1TG). The phenotypic analysis of RET/PTC1TG mice intercrossed with Patz1-knockout mice revealed that deficiency of both Patz1 alleles enhanced thyroid cancer incidence in RET/PTC1TG mice, but not the heterozygous knockout of the Patz1 gene. However, both RET/PTC1TG;Patz1+/− and RET/PTC1TG;Patz1−/− mice developed a more aggressive thyroid cancer phenotype—characterized by higher Ki-67 expression, presence of ATCs, and increased incidence of solid variants of PTC—than that shown by RET/PTC1TG; Patz1+/+ compound mice. These results confirm that PATZ1 downregulation has a critical role in thyroid carcinogenesis, showing that it cooperates with RET/PTC1 in thyroid cancer progression. Full article
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19 pages, 39803 KiB  
Review
Chromosomal Instability in Hodgkin Lymphoma: An In-Depth Review and Perspectives
by Corina Cuceu 1, William M. Hempel 1, Laure Sabatier 1, Jacques Bosq 2, Patrice Carde 3 and Radhia M’kacher 1,4,*
1 Laboratory of Radiobiology and Oncology and PROCyTOX, DRF, CEA, 91534 Paris-Saclay, France
2 Departement of Anapathology, Gustave Roussy Cancer Campus, 94805 Villejuif, France
3 Department of Hematology Gustave Roussy Cancer Campus, 94800 Villejuif, France
4 Cell Environment, DNA damages R&D, Oncology section, 75020 Paris, France
Cancers 2018, 10(4), 91; https://doi.org/10.3390/cancers10040091 - 26 Mar 2018
Cited by 34 | Viewed by 5954
Abstract
The study of Hodgkin lymphoma (HL), with its unique microenvironment and long-term follow-up, has provided exceptional insights into several areas of tumor biology. Findings in HL have not only improved our understanding of human carcinogenesis, but have also pioneered its translation into the [...] Read more.
The study of Hodgkin lymphoma (HL), with its unique microenvironment and long-term follow-up, has provided exceptional insights into several areas of tumor biology. Findings in HL have not only improved our understanding of human carcinogenesis, but have also pioneered its translation into the clinics. HL is a successful paradigm of modern treatment strategies. Nonetheless, approximately 15–20% of patients with advanced stage HL still die following relapse or progressive disease and a similar proportion of patients are over-treated, leading to treatment-related late sequelae, including solid tumors and organ dysfunction. The malignant cells in HL are characterized by a highly altered genomic landscape with a wide spectrum of genomic alterations, including somatic mutations, copy number alterations, complex chromosomal rearrangements, and aneuploidy. Here, we review the chromosomal instability mechanisms in HL, starting with the cellular origin of neoplastic cells and the mechanisms supporting HL pathogenesis, focusing particularly on the role of the microenvironment, including the influence of viruses and macrophages on the induction of chromosomal instability in HL. We discuss the emerging possibilities to exploit these aberrations as prognostic biomarkers and guides for personalized patient management. Full article
(This article belongs to the Special Issue Hodgkin's Lymphoma)
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22 pages, 12104 KiB  
Review
Targeting the Hippo Pathway Is a New Potential Therapeutic Modality for Malignant Mesothelioma
by Yoshitaka Sekido 1,2
1 Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan
2 Department of Cancer Genetics, Nagoya University Graduate School of Medicine, Nagoya 464-8681, Japan
Cancers 2018, 10(4), 90; https://doi.org/10.3390/cancers10040090 - 22 Mar 2018
Cited by 37 | Viewed by 8548
Abstract
Malignant mesothelioma (MM) constitutes a very aggressive tumor that arises from the pleural or peritoneal cavities and is highly refractory to conventional therapies. Several key genetic alterations are associated with the development and progression of MM including mutations of the CDKN2A/ARF, NF2 [...] Read more.
Malignant mesothelioma (MM) constitutes a very aggressive tumor that arises from the pleural or peritoneal cavities and is highly refractory to conventional therapies. Several key genetic alterations are associated with the development and progression of MM including mutations of the CDKN2A/ARF, NF2, and BAP1 tumor-suppressor genes. Notably, activating oncogene mutations are very rare; thus, it is difficult to develop effective inhibitors to treat MM. The NF2 gene encodes merlin, a protein that regulates multiple cell-signaling cascades including the Hippo pathway. MMs also exhibit inactivation of Hippo pathway components including LATS1/2, strongly suggesting that merlin-Hippo pathway dysregulation plays a key role in the development and progression of MM. Furthermore, Hippo pathway inactivation has been shown to result in constitutive activation of the YAP1/TAZ transcriptional coactivators, thereby conferring malignant phenotypes to mesothelial cells. Critical YAP1/TAZ target genes, including prooncogenic CCDN1 and CTGF, have also been shown to enhance the malignant phenotypes of MM cells. Together, these data indicate the Hippo pathway as a therapeutic target for the treatment of MM, and support the development of new strategies to effectively target the activation status of YAP1/TAZ as a promising therapeutic modality for this formidable disease. Full article
(This article belongs to the Special Issue Hippo Pathway in Cancer, towards Realization of the Hippo-Targeted Therapy)
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19 pages, 8121 KiB  
Article
Curcuminoids as EBV Lytic Activators for Adjuvant Treatment in EBV-Positive Carcinomas
by Octavia Ramayanti 1, Mitch Brinkkemper 1, Sandra A. W. M. Verkuijlen 1, Leni Ritmaleni 2, Mei Lin Go 3 and Jaap M. Middeldorp 1,*
1 Department of Pathology, VU University Medical Center, 1081HV Amsterdam, The Netherlands
2 Laboratory of Medicinal Chemistry, Gadjah Mada University, Yogyakarta 55281, Indonesia
3 Department of Pharmacy, National University of Singapore, Singapore 117543, Singapore
Cancers 2018, 10(4), 89; https://doi.org/10.3390/cancers10040089 - 22 Mar 2018
Cited by 23 | Viewed by 5750
Abstract
Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and [...] Read more.
Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and prevent virus production. CLVA treatment has proven safe in phase-I/II trials with promising clinical responses in patients with recurrent NPC. However, a major challenge is to maximize EBV lytic reactivation by CLVA. Curcumin, a dietary spice used in Asian countries, is known for its antitumor property and therapeutic potential. Novel curcuminoids that were developed to increase efficacy and bioavailability may serve as oral CLVA adjuvants. We investigated the potential of curcumin and its analogs (curcuminoids) to trigger the EBV lytic cycle in EBVaGC and NPC cells. EBV-reactivating effects were measured by immunoblot and immunofluorescence using monoclonal antibodies specific for EBV lytic proteins. Two of the hit compounds (41, EF24) with high lytic inducing activity were further studied for their synergistic or antagonistic effects when combined with GCb+VPA and analyzed by cytotoxicity and mRNA profiling assays to measure the EBV reactivation. Curcuminoid as a single agent significantly induced EBV reactivation in recombinant GC and NPC lines. The drug effects were dose- and time-dependent. Micromolar concentration of curcuminoid EF24 enhanced the CLVA effect in all cell systems except SNU719, a naturally infected EBVaGC cell that carries a more tightly latent viral genome. These findings indicated that EF24 has potential as EBV lytic activator and may serve as an adjuvant in CLVA treatment. Full article
(This article belongs to the Special Issue Epstein–Barr Virus Associated Cancers)
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11 pages, 3437 KiB  
Article
Use of the Ion PGM and the GeneReader NGS Systems in Daily Routine Practice for Advanced Lung Adenocarcinoma Patients: A Practical Point of View Reporting a Comparative Study and Assessment of 90 Patients
by Simon Heeke 1, Véronique Hofman 1,2,3, Elodie Long-Mira 1,2,3, Virginie Lespinet 2, Salomé Lalvée 2, Olivier Bordone 2, Camille Ribeyre 2, Virginie Tanga 2, Jonathan Benzaquen 1,4, Sylvie Leroy 4, Charlotte Cohen 5, Jérôme Mouroux 5, Charles Hugo Marquette 1,4, Marius Ilié 1,2,3 and Paul Hofman 1,2,3,*
1 Team 4, Institute of Research on Cancer and Aging of Nice (IRCAN), Inserm U1081, CNRS UMR7284, Université Côte d’Azur, CHU de Nice, 06107 Nice Cedex 2, France
2 Laboratory of Clinical and Experimental Pathology, Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, 06001 Nice Cedex 1, France
3 Hospital-Integrated Biobank (BB-0033-00025), Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, 06001 Nice Cedex 1, France
4 Department of Pulmonary Medicine and Oncology, Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, 06001 Nice Cedex 1, France
5 Department of Thoracic Surgery, Université Côte d’Azur, CHU de Nice, University Hospital Federation OncoAge, 06001 Nice Cedex 1, France
Cancers 2018, 10(4), 88; https://doi.org/10.3390/cancers10040088 - 21 Mar 2018
Cited by 15 | Viewed by 6010
Abstract
Background: With the integration of various targeted therapies into the clinical management of patients with advanced lung adenocarcinoma, next-generation sequencing (NGS) has become the technology of choice and has led to an increase in simultaneously interrogated genes. However, the broader adoption of [...] Read more.
Background: With the integration of various targeted therapies into the clinical management of patients with advanced lung adenocarcinoma, next-generation sequencing (NGS) has become the technology of choice and has led to an increase in simultaneously interrogated genes. However, the broader adoption of NGS for routine clinical practice is still hampered by sophisticated workflows, complex bioinformatics analysis and medical interpretation. Therefore, the performance of the novel QIAGEN GeneReader NGS system was compared to an in-house ISO-15189 certified Ion PGM NGS platform. Methods: Clinical samples from 90 patients (60 Retrospectively and 30 Prospectively) with lung adenocarcinoma were sequenced with both systems. Mutations were analyzed and EGFR, KRAS, BRAF, NRAS, ALK, PIK3CA and ERBB2 genes were compared and sampling time and suitability for clinical testing were assessed. Results: Both sequencing systems showed perfect concordance for the overlapping genes. Correlation of allele frequency was r2 = 0.93 for the retrospective patients and r2 = 0.81 for the prospective patients. Hands-on time and total run time were shorter using the PGM system, while the GeneReader platform provided good traceability and up-to-date interpretation of the results. Conclusion: We demonstrated the suitability of the GeneReader NGS system in routine practice in a clinical pathology laboratory setting. Full article
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22 pages, 1047 KiB  
Article
Study of the Influence of NanOx Parameters
by Caterina Monini *, Micaela Cunha, Etienne Testa and Michaёl Beuve
Institute of Nuclear Physics of Lyon (IPNL), Lyon 1 University, CNRS/IN2P3, 69622 Villeurbanne, France
Cancers 2018, 10(4), 87; https://doi.org/10.3390/cancers10040087 - 21 Mar 2018
Cited by 14 | Viewed by 3979
Abstract
NanOx is a new biophysical model that aims at predicting the biological effect of ions in the context of hadron therapy. It integrates the fully-stochastic nature of ionizing radiation both at micrometric and nanometric scales and also takes into account the production and [...] Read more.
NanOx is a new biophysical model that aims at predicting the biological effect of ions in the context of hadron therapy. It integrates the fully-stochastic nature of ionizing radiation both at micrometric and nanometric scales and also takes into account the production and diffusion of reactive chemical species. In order to further characterize the new framework, we discuss the meaning and relevance of most of the NanOx parameters by evaluating their influence on the linear-quadratic coefficient α and on the dose deposited to achieve 10% or 1% of cell survival, D 10 % or D 1 % , as a function of LET. We perform a theoretical study in which variations in the input parameters are propagated into the model predictions for HSG, V79 and CHO-K1 cells irradiated by monoenergetic protons and carbon ions. We conclude that, in the current version of NanOx, the modeling of a specific cell line relies on five parameters, which have to be adjusted to several experimental measurements: the average cellular nuclear radius, the linear-quadratic coefficients describing photon irradiations and the α values associated with two carbon ions of intermediate and high-LET values. This may have interesting implications toward a clinical application of the new biophysical model. Full article
(This article belongs to the Special Issue Proton and Carbon Ion Therapy)
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22 pages, 1168 KiB  
Review
New Insights from Elucidating the Role of LMP1 in Nasopharyngeal Carcinoma
by Kathy H. Y. Shair 1,2,*, Akhil Reddy 1 and Vaughn S. Cooper 2
1 Cancer Virology Program, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
2 Department of Microbiology and Molecular Genetics, and Center for Evolutionary Biology and Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
Cancers 2018, 10(4), 86; https://doi.org/10.3390/cancers10040086 - 21 Mar 2018
Cited by 33 | Viewed by 7078
Abstract
Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV) oncogenic protein that has no intrinsic enzymatic activity or sequence homology to cellular or viral proteins. The oncogenic potential of LMP1 has been ascribed to pleiotropic signaling properties initiated through protein-protein interactions in [...] Read more.
Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV) oncogenic protein that has no intrinsic enzymatic activity or sequence homology to cellular or viral proteins. The oncogenic potential of LMP1 has been ascribed to pleiotropic signaling properties initiated through protein-protein interactions in cytosolic membrane compartments, but the effects of LMP1 extend to nuclear and extracellular processes. Although LMP1 is one of the latent genes required for EBV-immortalization of B cells, the biology of LMP1 in the pathogenesis of the epithelial cancer nasopharyngeal carcinoma (NPC) is more complex. NPC is prevalent in specific regions of the world with high incidence in southeast China. The epidemiology and time interval from seroconversion to NPC onset in adults would suggest the involvement of multiple risk factors that complement the establishment of a latent and persistent EBV infection. The contribution of LMP1 to EBV pathogenesis in polarized epithelia has only recently begun to be elucidated. Furthermore, the LMP1 gene has emerged as one of the most divergent sequences in the EBV genome. This review will discuss the significance of recent advances in NPC research from elucidating LMP1 function in epithelial cells and lessons that could be learned from mining LMP1 sequence diversity. Full article
(This article belongs to the Special Issue Epstein–Barr Virus Associated Cancers)
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