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Cancers, Vol. 10, Pages 149: AZD1775 Increases Sensitivity to Olaparib and Gemcitabine in Cancer Cells with p53 Mutations
In this study, we assessed the effect of AZD1775 on endometrial and ovarian cancer cells in the presence of two DNA damaging agents, the PARP1 inhibitor, olaparib, and the chemotherapeutic agent, gemcitabine. We show that AZD1775 alone is effective as a therapeutic agent against some p53 mutated cell models. Moreover, the combination of AZD1775 with olaparib or gemcitabine is synergistic in cells with mutant p53 and constitutes a new approach that should be considered in the treatment of advanced and recurrent gynecologic cancer. (Source: Cancers)
Source: Cancers - May 19, 2018 Category: Cancer & Oncology Authors: Xiangbing Meng Jianling Bi Yujun Li Shujie Yang Yuping Zhang Mary Li Haitao Liu Yiyang Li Megan E. Mcdonald Kristina W. Thiel Kuo-Kuang Wen Xinhao Wang Meng Wu Kimberly K. Leslie Tags: Article Source Type: research

Cancers, Vol. 10, Pages 146: The Long Non-Coding RNA RP5-1024C24.1 and Its Associated-Gene MPPED2 Are Down-Regulated in Human Thyroid Neoplasias and Act as Tumour Suppressors
Conclusions: Taken together, these results demonstrate that RP5-1024C24.1 and MPPED2 might be considered as novel tumour suppressor genes whose loss of expression contributes to thyroid carcinogenesis. (Source: Cancers)
Source: Cancers - May 18, 2018 Category: Cancer & Oncology Authors: Romina Sepe Simona Pellecchia Pierre Serra Daniela D ’Angelo Antonella Federico Maddalena Raia Ricardo Cortez Cardoso Penha Myriam Decaussin-Petrucci Luigi Del Vecchio Alfredo Fusco Pierlorenzo Pallante Tags: Article Source Type: research

Cancers, Vol. 10, Pages 147: Bone Marrow Defects and Platelet Function: A Focus on MDS and CLL
drews The bloodstream typically contains >500 billion anucleate circulating platelets, derived from megakaryocytes in the bone marrow. This review will focus on two interesting aspects of bone marrow dysfunction and how this impacts on the quality of circulating platelets. In this regard, although megakaryocytes are from the myeloid lineage leading to granulocytes (including neutrophils), erythrocytes, and megakaryocytes/platelets, recent evidence has shown that defects in the lymphoid lineage leading to B cells, T cells, and natural killer (NK) cells also result in abnormal circulating platelets. Current ev...
Source: Cancers - May 18, 2018 Category: Cancer & Oncology Authors: Sarah Luu Elizabeth E. Gardiner Robert K. Andrews Tags: Review Source Type: research

Cancers, Vol. 10, Pages 148: p53-Autophagy-Metastasis Link
ovsky The tumor suppressor p53 as the “guardian of the genome” plays an essential role in numerous signaling pathways that control the cell cycle, cell death and in maintaining the integrity of the human genome. p53, depending on the intracellular localization, contributes to the regulation of various cell death pathways, including apoptosis, autophagy and necroptosis. Accumulated evidence suggests that this function of p53 is closely involved in the process of cancer development. Here, present knowledge concerning a p53-autophagy-metastasis link, as well as therapeutic approaches that influence this link, ...
Source: Cancers - May 18, 2018 Category: Cancer & Oncology Authors: Tatiana V. Denisenko Anastasia D. Pivnyuk Boris Zhivotovsky Tags: Review Source Type: research

Cancers, Vol. 10, Pages 145: [18F]FDG-PET/CT in Hodgkin Lymphoma: Current Usefulness and Perspectives
novas Functional imaging using 18-fluorodeoxyglycose ([18F]FDG) positron emission tomography combined with computed tomography (PET/CT) has become a major imaging modality in Hodgkin lymphoma. This imaging modality allows for a significant improvement in staging, increased sensitivity, which involves differentiating residual tumors from fibrosis during assessment, and highly impacts treatment decisions into new PET-driven strategies. This review presents the main scientific data concerning the current applications of [18F]FDG-PET/CT in Hodgkin lymphoma at baseline, interim, and the end of treatment evaluation along wit...
Source: Cancers - May 18, 2018 Category: Cancer & Oncology Authors: Salim Kanoun Cedric Rossi Olivier Casasnovas Tags: Review Source Type: research

Cancers, Vol. 10, Pages 144: Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro
In this study, the ability of alkylating agent temozolomide (TMZ)-induced autophagy to increase OAd replication and oncolysis in TNBC cells was evaluated. Human TNBC MDA-MB-231 and HCC1937 cells and mouse 4T1 cells were infected with an OAd expressing the red fluorescent protein mCherry on the virus capsid (OAdmCherry) alone or in combination with TMZ. TNBC cells treated with OAdmCherry/TMZ displayed greater mCherry and adenovirus (Ad) early region 1A (E1A) expression and enhanced cancer-cell killing compared to OAdmCherry or TMZ alone. The combined therapy-mediated cell death was associated with virus replication and accu...
Source: Cancers - May 17, 2018 Category: Cancer & Oncology Authors: Rodolfo Garza-Morales Roxana Gonzalez-Ramos Akiko Chiba Roberto Montes de Oca-Luna Lacey R. McNally Kelly M. McMasters Jorge G. Gomez-Gutierrez Tags: Article Source Type: research

Cancers, Vol. 10, Pages 143: DICER1 Syndrome: DICER1 Mutations in Rare Cancers
xford DICER1 syndrome is a rare genetic disorder that predisposes individuals to multiple cancer types. Through mutations of the gene encoding the endoribonuclease, Dicer, DICER1 syndrome disrupts the biogenesis and processing of miRNAs with subsequent disruption in control of gene expression. Since the first description of DICER1 syndrome, case reports have documented novel germline mutations of the DICER1 gene in patients with cancers as well as second site mutations that alter the function of the Dicer protein expressed. Here, we present a review of mutations in the DICER1 gene, the respective protein sequence chang...
Source: Cancers - May 15, 2018 Category: Cancer & Oncology Authors: Jake Robertson Cheryl Jorcyk Julia Oxford Tags: Review Source Type: research

Cancers, Vol. 10, Pages 142: A New Strategy to Control and Eradicate “Undruggable” Oncogenic K-RAS-Driven Pancreatic Cancer: Molecular Insights and Core Principles Learned from Developmental and Evolutionary Biology
Cancers, Vol. 10, Pages 142: A New Strategy to Control and Eradicate “Undruggable” Oncogenic K-RAS-Driven Pancreatic Cancer: Molecular Insights and Core Principles Learned from Developmental and Evolutionary Biology Cancers doi: 10.3390/cancers10050142 Authors: Robert Van Sciver Michael Lee Caroline Lee Alex Lafever Elizaveta Svyatova Kevin Kanda Amber Colliver Lauren Siewertsz van Reesema Angela Tang-Tan Vasilena Zheleva Monicah Bwayi Minglei Bian Rebecca Schmidt Lynn Matrisian Gloria Petersen Amy Tang Oncogenic K-RAS mutations are found in virtually all pancreatic cancers...
Source: Cancers - May 14, 2018 Category: Cancer & Oncology Authors: Robert Van Sciver Michael Lee Caroline Lee Alex Lafever Elizaveta Svyatova Kevin Kanda Amber Colliver Lauren Siewertsz van Reesema Angela Tang-Tan Vasilena Zheleva Monicah Bwayi Minglei Bian Rebecca Schmidt Lynn Matrisian Gloria Petersen Amy Tang Tags: Review Source Type: research

Cancers, Vol. 10, Pages 141: Role of the Bone Microenvironment in the Development of Painful Complications of Skeletal Metastases
hiozawa Cancer-induced bone pain (CIBP) is the most common and painful complication in patients with bone metastases. It causes a significant reduction in patient quality of life. Available analgesic treatments for CIBP, such as opioids that target the central nervous system, come with severe side effects as well as the risk of abuse and addiction. Therefore, alternative treatments for CIBP are desperately needed. Although the exact mechanisms of CIBP have not been fully elucidated, recent studies using preclinical models have demonstrated the role of the bone marrow microenvironment (e.g., osteoclasts, osteoblasts, ma...
Source: Cancers - May 10, 2018 Category: Cancer & Oncology Authors: Sun H. Park Matthew R. Eber D. Brooke Widner Yusuke Shiozawa Tags: Review Source Type: research

Cancers, Vol. 10, Pages 139: Proline-Rich Protein Tyrosine Kinase 2 in Inflammation and Cancer
ai Yang Focal adhesion kinase (FAK) and its homologous FAK-related proline-rich tyrosine kinase 2 (Pyk2) contain the same domain, exhibit high sequence homology and are defined as a distinct family of non-receptor tyrosine kinases. This group of kinases plays critical roles in cytoskeletal dynamics and cell adhesion by regulating survival and growth signaling. This review summarizes the physiological and pathological functions of Pyk2 in inflammation and cancers. In particular, overexpression of Pyk2 in cancerous tissues is correlated with poor outcomes. Pyk2 stimulates multiple oncogenic signaling pathways, such as Wn...
Source: Cancers - May 8, 2018 Category: Cancer & Oncology Authors: Xiangdong Zhu Yonghua Bao Yongchen Guo Wancai Yang Tags: Review Source Type: research

Cancers, Vol. 10, Pages 140: Toward the Discovery of a Novel Class of YAP –TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP–TEAD Protein–Protein Interface
Cancers, Vol. 10, Pages 140: Toward the Discovery of a Novel Class of YAP–TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP–TEAD Protein–Protein Interface Cancers doi: 10.3390/cancers10050140 Authors: Floriane Gibault Mathilde Coevoet Manon Sturbaut Amaury Farce Nicolas Renault Frédéric Allemand Jean-François Guichou Anne-Sophie Drucbert Catherine Foulon Romain Magnez Xavier Thuru Matthieu Corvaisier Guillemette Huet Philippe Chavatte Patricia Melnyk Fabrice Bailly Philippe Cotelle Intrinsically disordered protein YAP (yes-...
Source: Cancers - May 8, 2018 Category: Cancer & Oncology Authors: Floriane Gibault Mathilde Coevoet Manon Sturbaut Amaury Farce Nicolas Renault Fr édéric Allemand Jean-Fran çois Guichou Anne-Sophie Drucbert Catherine Foulon Romain Magnez Xavier Thuru Matthieu Corvaisier Guillemette Huet Philippe Chavatte Patricia Mel Tags: Article Source Type: research

Cancers, Vol. 10, Pages 138: Nuclear Export Inhibition for Pancreatic Cancer Therapy
ammad Pancreatic cancer is a deadly disease that is resistant to most available therapeutics. Pancreatic cancer to date has no effective drugs that could enhance the survival of patients once their disease has metastasized. There is a need for the identification of novel actionable drug targets in this unusually recalcitrant cancer. Nuclear protein transport is an important mechanism that regulates the function of several tumor suppressor proteins (TSPs) in a compartmentalization-dependent manner. High expression of the nuclear exporter chromosome maintenance region 1 (CRM1) or exportin 1 (XPO1), a common feature of se...
Source: Cancers - May 7, 2018 Category: Cancer & Oncology Authors: Irfana Muqbil Asfar S. Azmi Ramzi M. Mohammad Tags: Review Source Type: research

Cancers, Vol. 10, Pages 135: The Guardian of the Genome Revisited: p53 Downregulates Genes Required for Telomere Maintenance, DNA Repair, and Centromere Structure
k Toledo The p53 protein has been extensively studied for its capacity to prevent proliferation of cells with a damaged genome. Surprisingly, however, our recent analysis of mice expressing a hyperactive mutant p53 that lacks the C-terminal domain revealed that increased p53 activity may alter genome maintenance. We showed that p53 downregulates genes essential for telomere metabolism, DNA repair, and centromere structure and that a sustained p53 activity leads to phenotypic traits associated with dyskeratosis congenita and Fanconi anemia. This downregulation is largely conserved in human cells, which suggests that our...
Source: Cancers - May 6, 2018 Category: Cancer & Oncology Authors: El éonore Toufektchan Franck Toledo Tags: Review Source Type: research

Cancers, Vol. 10, Pages 136: Electron Nuclear Dynamics Simulations of Proton Cancer Therapy Reactions: Water Radiolysis and Proton- and Electron-Induced DNA Damage in Computational Prototypes
A. Morales Proton cancer therapy (PCT) utilizes high-energy proton projectiles to obliterate cancerous tumors with low damage to healthy tissues and without the side effects of X-ray therapy. The healing action of the protons results from their damage on cancerous cell DNA. Despite established clinical use, the chemical mechanisms of PCT reactions at the molecular level remain elusive. This situation prevents a rational design of PCT that can maximize its therapeutic power and minimize its side effects. The incomplete characterization of PCT reactions is partially due to the health risks associated with experimental/c...
Source: Cancers - May 6, 2018 Category: Cancer & Oncology Authors: Erico S. Teixeira Karthik Uppulury Austin J. Privett Christopher Stopera Patrick M. McLaurin Jorge A. Morales Tags: Article Source Type: research

Cancers, Vol. 10, Pages 137: YAP and TAZ in Lung Cancer: Oncogenic Role and Clinical Targeting
ndino Lung cancer is the leading cause of cancer death in the world and there is no current treatment able to efficiently treat the disease as the tumor is often diagnosed at an advanced stage. Moreover, cancer cells are often resistant or acquire resistance to the treatment. Further knowledge of the mechanisms driving lung tumorigenesis, aggressiveness, metastasization, and resistance to treatments could provide new tools for detecting the disease at an earlier stage and for a better response to therapy. In this scenario, Yes Associated Protein (YAP) and Trascriptional Coactivator with PDZ-binding motif (TAZ), the fin...
Source: Cancers - May 6, 2018 Category: Cancer & Oncology Authors: Federica Lo Sardo Sabrina Strano Giovanni Blandino Tags: Review Source Type: research

Cancers, Vol. 10, Pages 133: Translation Control by p53
Moira Sauane The translation of mRNAs plays a critical role in the regulation of gene expression and therefore, in the regulation of cell proliferation, differentiation and apoptosis. Unrestricted initiation of translation causes malignant transformation and plays a key role in the maintenance and progression of cancers. Translation initiation is regulated by the ternary complex and the eukaryotic initiation factor 4F (eIF4F) complex. The p53 tumor suppressor protein is the most well studied mammalian transcription factor that mediates a variety of anti-proliferative processes. Post-transcriptional mechanisms of gene ...
Source: Cancers - May 5, 2018 Category: Cancer & Oncology Authors: Justina Kasteri Dibash Das Xuelin Zhong Leah Persaud Ashleigh Francis Hilal Muharam Moira Sauane Tags: Perspective Source Type: research

Cancers, Vol. 10, Pages 134: The Prevalence of CD146 Expression in Breast Cancer Subtypes and Its Relation to Outcome
kens John W.M. Martens Stefan Sleijfer CD146, involved in epithelial-to-mesenchymal transition (EMT), might affect cancer aggressiveness. We here investigated the prevalence of CD146 expression in breast cancer subtypes, its relation to prognosis, the relation between CD146 and EMT and the outcome to tamoxifen. Primary breast cancer tissues from 1342 patients were available for this retrospective study and immunohistochemically stained for CD146. For survival analyses, pure prognosis was studied by only including lymph-node negative patients who did not receive (neo)adjuvant systemic treatment (n = 551). 11% of the...
Source: Cancers - May 5, 2018 Category: Cancer & Oncology Authors: Ingeborg E. de Kruijff Anna M. Timmermans Michael A. den Bakker Anita M.A.C. Trapman-Jansen Ren ée Foekens Marion E. Meijer-Van Gelder Esther Oomen-de Hoop Marcel Smid Antoinette Hollestelle Carolien H.M. van Deurzen John A. Foekens John W.M. Martens Ste Tags: Article Source Type: research

Cancers, Vol. 10, Pages 131: Insights of Crosstalk between p53 Protein and the MKK3/MKK6/p38 MAPK Signaling Pathway in Cancer
Bossi TP53 is universally recognized as a pivotal protein in cell-cycle fate and apoptotic induction and, unsurprisingly, it is one of the most commonly hijacked control mechanisms in cancer. Recently, the kinase MKK3 emerged as a potential therapeutic target in different types of solid tumor being linked to mutant p53 gain-of-function. In this review, we summarize the delicate relationship among p53 mutational status, MKK3/MKK6 and the downstream activated master kinase p38MAPK, dissecting a finely-tuned crosstalk, in a potentially cell-context dependent scenario that urges towards a deeper characterization of the dif...
Source: Cancers - May 3, 2018 Category: Cancer & Oncology Authors: Lorenzo Stramucci Angelina Pranteda Gianluca Bossi Tags: Review Source Type: research

Cancers, Vol. 10, Pages 132: Aptamers: Promising Tools for Cancer Diagnosis and Therapy
a The most common approaches to cancer treatment have been, for decades, based on surgical excision, radio- and/or chemotherapy, which, in spite of their modest survival benefits, still encounter several limitations, in part due to their lack of specificity [...] (Source: Cancers)
Source: Cancers - May 3, 2018 Category: Cancer & Oncology Authors: Laura Cerchia Tags: Editorial Source Type: research

Cancers, Vol. 10, Pages 129: EBV Positive Diffuse Large B Cell Lymphoma and Chronic Lymphocytic Leukemia Patients Exhibit Increased Anti-dUTPase Antibodies
iza The Epstein-Barr virus (EBV), which is a ubiquitous γ-herpesvirus, establishes a latent infection in more than 90% of the global adult population. EBV-associated malignancies have increased by 14.6% over the last 20 years, and account for approximately 1.5% of all cancers worldwide and 1.8% of all cancer deaths. However, the potential involvement/contribution of lytic proteins to the pathophysiology of EBV-associated cancers is not well understood. We have previously demonstrated that the EBV-deoxyuridine triphosphate nucleotidohydrolase (dUTPase) modulates innate and adaptive immune responses by enga...
Source: Cancers - May 1, 2018 Category: Cancer & Oncology Authors: Marshall Williams Maria Eugenia Ariza Tags: Article Source Type: research

Cancers, Vol. 10, Pages 130: The EBV-Encoded Oncoprotein, LMP1, Induces an Epithelial-to-Mesenchymal Transition (EMT) via Its CTAR1 Domain through Integrin-Mediated ERK-MAPK Signalling
Lawrence S. Young The Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) oncogene can induce profound effects on epithelial growth and differentiation including many of the features of the epithelial-to-mesenchymal transition (EMT). To better characterise these effects, we used the well-defined Madin Darby Canine Kidney (MDCK) epithelial cell model and found that LMP1 expression in these cells induces EMT as defined by characteristic morphological changes accompanied by loss of E-cadherin, desmosomal cadherin and tight junction protein expression. The induction of the EMT phenotype requi...
Source: Cancers - May 1, 2018 Category: Cancer & Oncology Authors: Mhairi A. Morris Louise Laverick Wenbin Wei Alexandra M. Davis Samantha O ’Neill Liam Wood Jack Wright Christopher W. Dawson Lawrence S. Young Tags: Article Source Type: research

Cancers, Vol. 10, Pages 128: Targeting Epigenetic Aberrations in Pancreatic Cancer, a New Path to Improve Patient Outcomes?
dez-Zapico Pancreatic cancer has one of the highest mortality rates among all types of cancers. The disease is highly aggressive and typically diagnosed in late stage making it difficult to treat. Currently, the vast majority of therapeutic regimens have only modest curative effects, and most of them are in the surgical/neo-adjuvant setting. There is a great need for new and more effective treatment strategies in common clinical practice. Previously, pathogenesis of pancreatic cancer was attributed solely to genetic mutations; however, recent advancements in the field have demonstrated that aberrant activation of epige...
Source: Cancers - April 28, 2018 Category: Cancer & Oncology Authors: Brooke D. Paradise Whitney Barham Mart ín E. Fernandez-Zapico Tags: Review Source Type: research

Cancers, Vol. 10, Pages 127: Responses to the Selective Bruton ’s Tyrosine Kinase (BTK) Inhibitor Tirabrutinib (ONO/GS-4059) in Diffuse Large B-cell Lymphoma Cell Lines
Cancers, Vol. 10, Pages 127: Responses to the Selective Bruton’s Tyrosine Kinase (BTK) Inhibitor Tirabrutinib (ONO/GS-4059) in Diffuse Large B-cell Lymphoma Cell Lines Cancers doi: 10.3390/cancers10040127 Authors: Ryohei Kozaki Meike Vogler Harriet Walter Sandrine Jayne David Dinsdale Reiner Siebert Martin Dyer Toshio Yoshizawa Bruton’s tyrosine kinase (BTK) is a key regulator of the B-cell receptor signaling pathway, and aberrant B-cell receptor (BCR) signaling has been implicated in the survival of malignant B-cells. However, responses of the diffuse large B-cell lymphoma (DLBCL) to inhi...
Source: Cancers - April 23, 2018 Category: Cancer & Oncology Authors: Ryohei Kozaki Meike Vogler Harriet Walter Sandrine Jayne David Dinsdale Reiner Siebert Martin Dyer Toshio Yoshizawa Tags: Article Source Type: research

Cancers, Vol. 10, Pages 125: Selective Inhibition of Histone Deacetylation in Melanoma Increases Targeted Gene Delivery by a Bacteriophage Viral Vector
We report that the HDAC inhibitor C1A increased AAVP-mediated transgene expression by up to ~9-fold. These findings indicate that selective HDAC inhibition is a promising adjuvant treatment for increasing the therapeutic value of AAVP. (Source: Cancers)
Source: Cancers - April 21, 2018 Category: Cancer & Oncology Authors: Samuel Campbell Keittisak Suwan Sajee Waramit Eric Ofori Aboagye Amin Hajitou Tags: Brief Report Source Type: research

Cancers, Vol. 10, Pages 126: Hypoxia-Induced Cisplatin Resistance in Non-Small Cell Lung Cancer Cells Is Mediated by HIF-1 α and Mutant p53 and Can Be Overcome by Induction of Oxidative Stress
This study focusses on the role of hypoxia-inducible factor-1α (HIF-1α) and the p53 tumor suppressor protein in hypoxia-induced cisplatin resistance in non-small cell lung cancer (NSCLC) cells and the potential of APR-246 to overcome this resistance. We observed that hypoxia-induced cisplatin resistance only occurred in the p53 mutant NCI-H2228Q331* cell line, and not in the wild type A549 and mutant NCI-H1975R273H cell lines. Cisplatin reduced HIF-1α protein levels in NCI-H2228Q331* cells, leading to a shift in expression from HIF-1α-dependent to p53-dependent transc...
Source: Cancers - April 21, 2018 Category: Cancer & Oncology Authors: Christophe Deben Vanessa Deschoolmeester Jorrit De Waele Julie Jacobs Jolien Van den Bossche An Wouters Marc Peeters Christian Rolfo Evelien Smits Filip Lardon Patrick Pauwels Tags: Article Source Type: research

Cancers, Vol. 10, Pages 124: Oncolytic Virotherapy versus Cancer Stem Cells: A Review of Approaches and Mechanisms
arner A growing body of evidence suggests that a subset of cells within tumors are resistant to conventional treatment modalities and may be responsible for disease recurrence. These cells are called cancer stem cells (CSC), which share properties with normal stem cells including self-renewal, pluripotency, drug resistance, and the ability to maintain quiescence. While most conventional therapies can efficiently destroy rapidly dividing cancer cells comprising the bulk of a tumor, they often fail to kill the less abundant and quiescent CSCs. Furthermore, killing of only differentiated cells in the tumor may actually al...
Source: Cancers - April 19, 2018 Category: Cancer & Oncology Authors: Shyambabu Chaurasiya Nanhai G. Chen Susanne G. Warner Tags: Review Source Type: research

Cancers, Vol. 10, Pages 123: Innovative Diagnostic Methods for Early Prostate Cancer Detection through Urine Analysis: A Review
Laura Capelli Prostate cancer is the second most common cause of cancer death among men. It is an asymptomatic and slow growing tumour, which starts occurring in young men, but can be detected only around the age of 40–50. Although its long latency period and potential curability make prostate cancer a perfect candidate for screening programs, the current procedure lacks in specificity. Researchers are rising to the challenge of developing innovative tools able of detecting the disease during its early stage that is the most curable. In recent years, the interest in characterisation of biological fluids a...
Source: Cancers - April 18, 2018 Category: Cancer & Oncology Authors: Carmen Bax Gianluigi Taverna Lidia Eusebio Selena Sironi Fabio Grizzi Giorgio Guazzoni Laura Capelli Tags: Review Source Type: research

Cancers, Vol. 10, Pages 120: Perspective: Contribution of Epstein –Barr virus (EBV) Reactivation to the Carcinogenicity of Nasopharyngeal Cancer Cells
Cancers, Vol. 10, Pages 120: Perspective: Contribution of Epstein–Barr virus (EBV) Reactivation to the Carcinogenicity of Nasopharyngeal Cancer Cells Cancers doi: 10.3390/cancers10040120 Authors: Chung-Chun Wu Chih-Yeu Fang Sheng-Yen Huang Shih-Hsin Chiu Chia-Huei Lee Jen-Yang Chen Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma derived from the epithelium of the post-nasal cavity, with a unique geographic and ethnic distribution. Epstein–Barr virus (EBV) is an etiological agent of NPC, but how it contributes to carcinogenesis is not completely clear. Although it is thought...
Source: Cancers - April 17, 2018 Category: Cancer & Oncology Authors: Chung-Chun Wu Chih-Yeu Fang Sheng-Yen Huang Shih-Hsin Chiu Chia-Huei Lee Jen-Yang Chen Tags: Perspective Source Type: research

Cancers, Vol. 10, Pages 121: Ubiquitin-Dependent Regulation of the Mammalian Hippo Pathway: Therapeutic Implications for Cancer
ler The Hippo pathway serves as a key barrier for oncogenic transformation. It acts by limiting the activity of the proto-oncogenes YAP and TAZ. Reduced Hippo signaling and elevated YAP/TAZ activities are frequently observed in various types of tumors. Emerging evidence suggests that the ubiquitin system plays an important role in regulating Hippo pathway activity. Deregulation of ubiquitin ligases and of deubiquitinating enzymes has been implicated in increased YAP/TAZ activity in cancer. In this article, we review recent insights into the ubiquitin-mediated regulation of the mammalian Hippo pathway, its deregulation ...
Source: Cancers - April 17, 2018 Category: Cancer & Oncology Authors: Thanh Hung Nguyen Jan-Michael Kugler Tags: Review Source Type: research

Cancers, Vol. 10, Pages 122: The Hippo-YAP Pathway Regulates 3D Organ Formation and Homeostasis
ina The vertebrate body shape is formed by the specific sizes and shapes of its resident tissues and organs, whose alignments are essential for proper functioning. To maintain tissue and organ shape, and thereby function, it is necessary to remove senescent, transformed, and/or damaged cells, which impair function and can lead to tumorigenesis. However, the molecular mechanisms underlying three-dimensional (3D) organ formation and homeostasis are not fully clear. Yes-associated protein (YAP) is a transcriptional co-activator that is involved in organ size control and tumorigenesis. Recently, we reported that YAP is ess...
Source: Cancers - April 17, 2018 Category: Cancer & Oncology Authors: Erika Ishihara Hiroshi Nishina Tags: Commentary Source Type: research

Cancers, Vol. 10, Pages 119: NF- κB Signaling Regulates Epstein–Barr Virus BamHI-Q-Driven EBNA1 Expression
Cancers, Vol. 10, Pages 119: NF-κB Signaling Regulates Epstein–Barr Virus BamHI-Q-Driven EBNA1 Expression Cancers doi: 10.3390/cancers10040119 Authors: Rob Verhoeven Shuang Tong Jingfeng Zong Yixin Chen Sai-Wah Tsao Jianji Pan Honglin Chen Epstein–Barr virus (EBV) nuclear antigen 1 (EBNA1) is one of the few viral proteins expressed by EBV in nasopharyngeal carcinoma (NPC), most likely because of its essential role in maintaining the viral genome in EBV-infected cells. In NPC, EBNA1 expression is driven by the BamHI-Q promoter (Qp), which is regulated by both cellular and viral factors....
Source: Cancers - April 16, 2018 Category: Cancer & Oncology Authors: Rob Verhoeven Shuang Tong Jingfeng Zong Yixin Chen Sai-Wah Tsao Jianji Pan Honglin Chen Tags: Article Source Type: research

Cancers, Vol. 10, Pages 118: Roles of Polyploid/Multinucleated Giant Cancer Cells in Metastasis and Disease Relapse Following Anticancer Treatment
urray Tumors and tumor-derived cell lines contain polyploid giant cells with significantly elevated genomic content, often with multiple nuclei. The frequency of giant cells can increase markedly following anticancer treatment. Although giant cells enter a dormant phase and therefore do not form macroscopic colonies (aggregates of ≥50 cells) in the conventional in vitro colony formation assay, they remain viable and metabolically active. The purpose of this commentary is to underscore the potential importance of polyploid/multinucleated giant cells in metastasis and cancer recurrence following exposure to anticancer...
Source: Cancers - April 15, 2018 Category: Cancer & Oncology Authors: Razmik Mirzayans Bonnie Andrais David Murray Tags: Commentary Source Type: research

Cancers, Vol. 10, Pages 117: Public Health Care Financing and the Costs of Cancer Care: A Cross-National Analysis
tan Expenditure and financing aspects in the healthcare system in general, and in cancer care in particular, are subjects of increasing concern to the medical community. Nowadays, it is imperative for the healthcare system to respond to the challenge of universal access to quality healthcare, by measuring the financial resources within the healthcare sector. The purpose of this review is to highlight the major gaps in the healthcare expenditures for all types of care, as well as on cancer and anti-cancer drugs across 28 European Union member states. The indicators taken into account are divided into two major groups: (...
Source: Cancers - April 12, 2018 Category: Cancer & Oncology Authors: Ana Voda Ionel Bostan Tags: Article Source Type: research

Cancers, Vol. 10, Pages 114: Immune Response against ALK in Children with ALK-Positive Anaplastic Large Cell Lymphoma
lm Woessmann Patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) mount a humoral and cellular immune response against ALK. More than 90% of children and adolescents with ALK-positive ALCL have detectable anti-ALK antibodies in serum or plasma, and the antibody titer inversely correlates with the risk of relapse. ALK-specific CD8 and CD4 T cell responses have been described in patients with ALK-positive ALCL. Vaccination with ALK DNA led to protection against lymphoma growth in a murine model. Collectively, these data suggest that the ALK-specific immune response is involved in ...
Source: Cancers - April 10, 2018 Category: Cancer & Oncology Authors: Serena Stadler Vijay Singh Fabian Kn örr Christine Damm-Welk Wilhelm Woessmann Tags: Review Source Type: research

Cancers, Vol. 10, Pages 113: ALK in Neuroblastoma: Biological and Therapeutic Implications
ner Neuroblastoma (NB) is the most common and deadly solid tumour in children. Despite the development of new treatment options for high-risk NB, over half of patients relapse and five-year survival remains at 40–50%. Therefore, novel treatment strategies aimed at providing long-term disease remission are urgently sought. ALK, encoding the anaplastic lymphoma kinase receptor, is altered by gain-of-function point mutations in around 14% of high-risk NB and represents an ideal therapeutic target given its low or absent expression in healthy tissue postnatally. Small-molecule inhibitors of Anaplastic Lymphoma Kinase...
Source: Cancers - April 10, 2018 Category: Cancer & Oncology Authors: Ricky Trigg Suzanne Turner Tags: Review Source Type: research

Cancers, Vol. 10, Pages 115: YAP/TAZ Activation as a Target for Treating Metastatic Cancer
Lamar Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ) have both emerged as important drivers of cancer progression and metastasis. YAP and TAZ are often upregulated or nuclear localized in aggressive human cancers. There is abundant experimental evidence demonstrating that YAP or TAZ activation promotes cancer formation, tumor progression, and metastasis. In this review we summarize the evidence linking YAP/TAZ activation to metastasis, and discuss the roles of YAP and TAZ during each step of the metastatic cascade. Collectively, this evidence strongly suggests that inappropri...
Source: Cancers - April 10, 2018 Category: Cancer & Oncology Authors: Janine Warren Yuxuan Xiao John Lamar Tags: Review Source Type: research

Cancers, Vol. 10, Pages 116: Proton Beam Therapy Alone for Intermediate- or High-Risk Prostate Cancer: An Institutional Prospective Cohort Study
kashi Ogino The role of proton beam therapy (PBT) as monotherapy for localized prostate cancer (PCa) remains unclear. The purpose of this study was to evaluate the efficacy and adverse events of PBT alone for these patients. Between January 2011 and July 2014, 218 patients with intermediate- and high-risk PCa who declined androgen deprivation therapy (ADT) were enrolled to the study and were treated with PBT following one of the following protocols: 74 Gray (GyE) with 37 fractions (fr) (74 GyE/37 fr), 78 GyE/39 fr, and 70 GyE/28 fr. The 5-year progression-free survival rate in the intermediate- and high-risk groups was...
Source: Cancers - April 10, 2018 Category: Cancer & Oncology Authors: Takeshi Arimura Takashi Yoshiura Kyoko Matsukawa Naoaki Kondo Ikumi Kitano Takashi Ogino Tags: Article Source Type: research

Cancers, Vol. 10, Pages 112: Construction and Characterization of a Humanized Anti-Epstein-Barr Virus gp350 Antibody with Neutralizing Activity in Cell Culture
fieri Acute Epstein-Barr virus (EBV) infection in immunosuppressed transplant patients can give rise to a malignant B-cell proliferation known as post-transplant lymphoproliferative disease (PTLD). The EBV major virion surface glycoprotein (gp)350 is a principal target of naturally occurring neutralizing antibodies and is viewed as the best target to prevent acute infection and PTLD in at-risk transplant recipients. We have constructed a humanized (hu) version of the murine anti-gp350 neutralizing monoclonal antibody 72a1. The hu72a1 IgG1 antibody displayed no significant anti-mouse activity, recognized both gp350 and ...
Source: Cancers - April 9, 2018 Category: Cancer & Oncology Authors: Jerome Tanner Jing Hu Caroline Alfieri Tags: Article Source Type: research

Cancers, Vol. 10, Pages 110: New Challenges in Targeting Signaling Pathways in Acute Lymphoblastic Leukemia by NGS Approaches: An Update
cute;s María Hernández-Rivas The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA r...
Source: Cancers - April 7, 2018 Category: Cancer & Oncology Authors: Adri án Montaño Maribel Forero-Castro Darnel Marchena-Mendoza Roc ío Benito Jes ús María Hernández-Rivas Tags: Review Source Type: research

Cancers, Vol. 10, Pages 111: Proton Partial Breast Irradiation: Detailed Description of Acute Clinico-Radiologic Effects
er Wendy Woodward Introduction: Accelerated partial breast irradiation (APBI) with protons results in a very different acute effect profile than standard whole breast irradiation. We reviewed our initial experience with proton APBI and felt that a detailed description of these effects were needed to permit a common tool to compare experience with this developing technology. Methods: Sixty sequential patients treated with proton APBI on a prospective protocol were evaluated and 43 patients with a minimum six-month follow-up underwent detailed photographic and radiologic analysis. The tumorectomy cavity plus an additio...
Source: Cancers - April 7, 2018 Category: Cancer & Oncology Authors: Valentina Ovalle Eric A. Strom Simona Shaitelman Karen Hoffman Richard Amos George Perkins Welela Tereffe Benjamin D. Smith Michael Stauder Wendy Woodward Tags: Article Source Type: research

Cancers, Vol. 10, Pages 109: EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers
in Fahraeus The presence of the Epstein-Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) protein in all EBV-carrying tumours constitutes a marker that distinguishes the virus-associated cancer cells from normal cells and thereby offers opportunities for targeted therapeutic intervention. EBNA1 is essential for viral genome maintenance and also for controlling viral gene expression and without EBNA1, the virus cannot persist. EBNA1 itself has been linked to cell transformation but the underlying mechanism of its oncogenic activity has been unclear. However, recent data are starting to shed light on its growth-promotin...
Source: Cancers - April 6, 2018 Category: Cancer & Oncology Authors: Joanna B. Wilson Evelyne Manet Henri Gruffat Pierre Busson Marc Blondel Robin Fahraeus Tags: Review Source Type: research

Cancers, Vol. 10, Pages 108: Immunohistochemistry for Diagnosis of Metastatic Carcinomas of Unknown Primary Site
us Ilié Immunohistochemistry has become an essential ancillary examination for the identification and classification of carcinomas of unknown primary site (CUPs). Over the last decade, the diagnostic accuracy of organ- or tumour-specific immunomarkers and the clinical validation of effective immunohistochemical panels has improved significantly. When dealing with small sample sizes, diagnostic accuracy is crucial, particularly in the current era of targeted molecular and immune-based therapies. Effective systematic use of appropriate immunohistochemical panels enables accurate classification of most of the undif...
Source: Cancers - April 5, 2018 Category: Cancer & Oncology Authors: Janick Selves Elodie Long-Mira Marie-Christine Mathieu Philippe Rochaix Marius Ili é Tags: Review Source Type: research

Cancers, Vol. 10, Pages 105: Inhibiting TRK Proteins in Clinical Cancer Therapy
Lo Gene rearrangements resulting in the aberrant activity of tyrosine kinases have been identified as drivers of oncogenesis in a variety of cancers. The tropomyosin receptor kinase (TRK) family of tyrosine receptor kinases is emerging as an important target for cancer therapeutics. The TRK family contains three members, TRKA, TRKB, and TRKC, and these proteins are encoded by the genes NTRK1, NTRK2, and NTRK3, respectively. To activate TRK receptors, neurotrophins bind to the extracellular region stimulating dimerization, phosphorylation, and activation of downstream signaling pathways. Major known downstream pathways...
Source: Cancers - April 4, 2018 Category: Cancer & Oncology Authors: Allison M. Lange Hui-Wen Lo Tags: Review Source Type: research

Cancers, Vol. 10, Pages 106: Interplay of Viral Infection, Host Cell Factors and Tumor Microenvironment in the Pathogenesis of Nasopharyngeal Carcinoma
Tsang Undifferentiated nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV) infection. In addition, heavy infiltration of leukocytes is a common characteristic of EBV-associated NPC. It has long been suggested that substantial and interactive impacts between cancer and stromal cells create a tumor microenvironment (TME) to promote tumorigenesis. The coexistence of tumor-infiltrating lymphocytes with EBV-infected NPC cells represents a distinct TME which supports immune evasion and cancer development from the early phase of EBV infection. Intracellularly, EBV-encoded viral products alter h...
Source: Cancers - April 4, 2018 Category: Cancer & Oncology Authors: Shaina Chor Mei Huang Sai Wah Tsao Chi Man Tsang Tags: Review Source Type: research

Cancers, Vol. 10, Pages 107: The Pathological Spectrum of Systemic Anaplastic Large Cell Lymphoma (ALCL)
alko Fend Anaplastic large cell lymphoma (ALCL) represents a group of malignant T-cell lymphoproliferations that share morphological and immunophenotypical features, namely strong CD30 expression and variable loss of T-cell markers, but differ in clinical presentation and prognosis. The recognition of anaplastic lymphoma kinase (ALK) fusion proteins as a result of chromosomal translocations or inversions was the starting point for the distinction of different subgroups of ALCL. According to their distinct clinical settings and molecular findings, the 2016 revised World Health Organization (WHO) classification recognize...
Source: Cancers - April 4, 2018 Category: Cancer & Oncology Authors: Ivonne A. Montes-Mojarro Julia Steinhilber Irina Bonzheim Leticia Quintanilla-Martinez Falko Fend Tags: Review Source Type: research

Cancers, Vol. 10, Pages 104: The Critical Role of Inflammation in the Pathogenesis and Progression of Myeloid Malignancies
ischman Hematopoietic stem cells (HSCs) maintain an organism’s immune system for a lifetime, and derangements in HSC proliferation and differentiation result in hematologic malignancies. Chronic inflammation plays a contributory if not causal role in HSC dysfunction. Inflammation induces HSC exhaustion, which promotes the emergence of mutant clones that may be resistant to an inflammatory microenvironment; this likely promotes the onset of a myeloid hematologic malignancy. Inflammatory cytokines are characteristically high in patients with myeloid malignancies and are linked to disease initiation, symptom burden,...
Source: Cancers - April 3, 2018 Category: Cancer & Oncology Authors: Brianna Craver Kenza El Alaoui Robyn Scherber Angela Fleischman Tags: Review Source Type: research

Cancers, Vol. 10, Pages 103: Role of Gene Therapy in Pancreatic Cancer —A Review
Cancers, Vol. 10, Pages 103: Role of Gene Therapy in Pancreatic Cancer—A Review Cancers doi: 10.3390/cancers10040103 Authors: Mizuho Sato-Dahlman Keith Wirth Masato Yamamoto Mortality from pancreatic ductal adenocarcinoma (PDAC) has remained essentially unchanged for decades and its relative contribution to overall cancer death is projected to only increase in the coming years. Current treatment for PDAC includes aggressive chemotherapy and surgical resection in a limited number of patients, with median survival of optimal treatment rather dismal. Recent advances in gene therapies offer novel opportunitie...
Source: Cancers - April 3, 2018 Category: Cancer & Oncology Authors: Mizuho Sato-Dahlman Keith Wirth Masato Yamamoto Tags: Review Source Type: research

Cancers, Vol. 10, Pages 101: Epigenetic Modifications as Biomarkers of Tumor Development, Therapy Response, and Recurrence across the Cancer Care Continuum
ato Aberrant epigenetic modifications are an early event in carcinogenesis, with the epigenetic landscape continuing to change during tumor progression and metastasis—these observations suggest that specific epigenetic modifications could be used as diagnostic and prognostic biomarkers for many cancer types. DNA methylation, post-translational histone modifications, and non-coding RNAs are all dysregulated in cancer and are detectable to various degrees in liquid biopsies such as sputum, urine, stool, and blood. Here, we will focus on the application of liquid biopsies, as opposed to tissue biopsies, because of t...
Source: Cancers - April 1, 2018 Category: Cancer & Oncology Authors: Margaret Thomas Paola Marcato Tags: Review Source Type: research

Cancers, Vol. 10, Pages 102: EBV+ and MSI Gastric Cancers Harbor High PD-L1/PD-1 Expression and High CD8+ Intratumoral Lymphocytes
a Chiaravalli Both EBV+ and MSI gastric cancers (GCs) have high lymphoid infiltration which is rare in MSS/EBV− cancers. PD-L1/PD-1 interaction leads to a down-regulated immune response and it is one of the most promising targets for gastric cancer immunotherapy. PD-L1/PD-1 and CD8 expression were immunohistochemically investigated in a series of 169 FFPE GCs, including 33 EBV+, 59 MSI and 77 MSS/EBV− cases. PD-L1 membrane immunoreactivity in more than 5% of tumor cells was present in 31/169 GCs and was associated with high levels of CD8 intraepithelial lymphocytes (TILs; p < 0.001). PD-L1+ cases...
Source: Cancers - April 1, 2018 Category: Cancer & Oncology Authors: Simona De Rosa Nora Sahnane Maria Tibiletti Francesca Magnoli Alessandro Vanoli Fausto Sessa Anna Chiaravalli Tags: Article Source Type: research

Cancers, Vol. 10, Pages 100: Bladder Cancer: New Insights into Its Molecular Pathology
a Bladder cancer is one of the most prevalent cancers worldwide. Unfortunately, there have been few advances in its clinical management due to a poor understanding of the correlations between its molecular and clinical features. Mounting evidence suggests that bladder cancer comprises a group of molecularly heterogeneous diseases that undergo a variety of clinical courses and possess diverse therapeutic responses. Owing to the close association between its molecular subtypes and clinicopathological features, specific therapeutic strategies have recently been suggested. This review summarizes the current understanding o...
Source: Cancers - April 1, 2018 Category: Cancer & Oncology Authors: Kentaro Inamura Tags: Review Source Type: research