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Cancers, Vol. 9, Pages 110: Integrins as Therapeutic Targets: Successes and Cancers
odman Integrins are transmembrane receptors that are central to the biology of many human pathologies. Classically mediating cell-extracellular matrix and cell-cell interaction, and with an emerging role as local activators of TGFβ, they influence cancer, fibrosis, thrombosis and inflammation. Their ligand binding and some regulatory sites are extracellular and sensitive to pharmacological intervention, as proven by the clinical success of seven drugs targeting them. The six drugs on the market in 2016 generated revenues of some US$3.5 billion, mainly from inhibitors of α4-series integrins. In this review we...
Source: Cancers - August 23, 2017 Category: Cancer & Oncology Authors: Sabine Raab-Westphal John Marshall Simon Goodman Tags: Review Source Type: research

Cancers, Vol. 9, Pages 109: Understanding Resistance Mechanisms and Expanding the Therapeutic Utility of PARP Inhibitors
Tan Poly-(ADP-ribose) polymerase (PARP) inhibitors act through synthetic lethality in cells with defects in homologous recombination (HR) DNA repair caused by molecular aberrations such as BRCA mutations, and is approved for treatment in ovarian cancer, with promising clinical activity against other HR defective tumors including breast and prostate cancers. Three PARP inhibitors have been FDA approved, while another two have shown promising activity and are in late stage development. Nonetheless, both primary and secondary resistance to PARP inhibition have led to treatment failure, and the development of predictive bi...
Source: Cancers - August 22, 2017 Category: Cancer & Oncology Authors: Joline Lim David S. P. Tan Tags: Review Source Type: research

Cancers, Vol. 9, Pages 108: National and Subnational Population-Based Incidence of Cancer in Thailand: Assessing Cancers with the Highest Burdens
Vatanasapt Hutcha Sriplung In Thailand, five cancer types—breast, cervical, colorectal, liver and lung cancer—contribute to over half of the cancer burden. The magnitude of these cancers must be quantified over time to assess previous health policies and highlight future trajectories for targeted prevention efforts. We provide a comprehensive assessment of these five cancers nationally and subnationally, with trend analysis, projections, and number of cases expected for the year 2025 using cancer registry data. We found that breast (average annual percent change (AAPC): 3.1%) and colorectal cancer (female...
Source: Cancers - August 17, 2017 Category: Cancer & Oncology Authors: Shama Virani Surichai Bilheem Wasan Chansaard Imjai Chitapanarux Karnchana Daoprasert Somsak Khuanchana Atit Leklob Donsuk Pongnikorn Laura Rozek Surattaya Siriarechakul Krittika Suwanrungruang Sukit Tassanasunthornwong Patravoot Vatanasapt Hutcha Sriplun Tags: Article Source Type: research

Cancers, Vol. 9, Pages 106: ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients
n Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor ...
Source: Cancers - August 12, 2017 Category: Cancer & Oncology Authors: Paul Hofman Tags: Review Source Type: research

Cancers, Vol. 9, Pages 107: ALK in Non-Small Cell Lung Cancer (NSCLC) Pathobiology, Epidemiology, Detection from Tumor Tissue and Algorithm Diagnosis in a Daily Practice
n Patients with advanced-stage non-small cell lung carcinoma (NSCLC) harboring an ALK rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. Several increasingly effective ALK inhibitors are now available for treatment of patients. However, despite an initial favorable response to treatment, in most cases relapse or progression occurs due to resistance mechanisms mainly caused by mutations in the tyrosine kinase domain of ALK. The detection of an ALK rearrangement is pivotal and can be done using different methods, which have variable sensitivity and specificity depending, in p...
Source: Cancers - August 12, 2017 Category: Cancer & Oncology Authors: Paul Hofman Tags: Review Source Type: research

Cancers, Vol. 9, Pages 105: The Role of Cancer-Derived Exosomes in Tumorigenicity & amp; Epithelial-to-Mesenchymal Transition
Cancers, Vol. 9, Pages 105: The Role of Cancer-Derived Exosomes in Tumorigenicity & Epithelial-to-Mesenchymal Transition Cancers doi: 10.3390/cancers9080105 Authors: Robert Blackwell Kimberly Foreman Gopal Gupta Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their basement membrane interaction and acquire a more migratory, mesenchymal phenotype. EMT has been implicated in cancer cell progression, as cells transform and increase motility and invasiveness, induce angiogenesis, and metastasize. Exosomes are 30–100 nm membrane-bound vesicles that are formed and ...
Source: Cancers - August 10, 2017 Category: Cancer & Oncology Authors: Robert Blackwell Kimberly Foreman Gopal Gupta Tags: Review Source Type: research

Cancers, Vol. 9, Pages 104: Complex Determinants of Epithelial: Mesenchymal Phenotypic Plasticity in Ovarian Cancer
Stack Unlike most epithelial malignancies which metastasize hematogenously, metastasis of epithelial ovarian cancer (EOC) occurs primarily via transcoelomic dissemination, characterized by exfoliation of cells from the primary tumor, avoidance of detachment-induced cell death (anoikis), movement throughout the peritoneal cavity as individual cells and multi-cellular aggregates (MCAs), adhesion to and disruption of the mesothelial lining of the peritoneum, and submesothelial matrix anchoring and proliferation to generate widely disseminated metastases. This exceptional microenvironment is highly permissive for phenotypi...
Source: Cancers - August 9, 2017 Category: Cancer & Oncology Authors: Yuliya Klymenko Oleg Kim M. Stack Tags: Review Source Type: research

Cancers, Vol. 9, Pages 103: Secondary Intracranial Tumors Following Radiotherapy for Pituitary Adenomas: A Systematic Review
Cancers, Vol. 9, Pages 103: Secondary Intracranial Tumors Following Radiotherapy for Pituitary Adenomas: A Systematic Review Cancers doi: 10.3390/cancers9080103 Authors: Ryuya Yamanaka Eisuke Abe Toshiteru Sato Azusa Hayano Yasuo Takashima Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by radiotherapy are at risk of development of secondary malignancies. We conducted a comprehensive literature review of the secondary intracranial tumors that occurred following radiotherapy to pituitary aden...
Source: Cancers - August 8, 2017 Category: Cancer & Oncology Authors: Ryuya Yamanaka Eisuke Abe Toshiteru Sato Azusa Hayano Yasuo Takashima Tags: Review Source Type: research

Cancers, Vol. 9, Pages 102: Significance of microRNAs in Androgen Signaling and Prostate Cancer Progression
Inoue The androgen receptor (AR) plays important roles in prostate cancer development and prostate tumor growth. After binding to androgens, AR functions as a nuclear receptor and translocates to the nucleus to bind to specific AR-binding sites (ARBSs). AR regulates epigenetic factor recruitments to activate its downstream signaling. Although androgen deprivation therapy (ADT) is initially useful for prostate cancer patients, most patients eventually show resistance with hormone-refractory prostate cancers (HRPCs) or castration-resistant prostate cancers (CRPCs). Thus, new therapeutic strategies targeting HRPCs/CRPCs s...
Source: Cancers - August 7, 2017 Category: Cancer & Oncology Authors: Ken-ichi Takayama Aya Misawa Satoshi Inoue Tags: Review Source Type: research

Cancers, Vol. 9, Pages 100: Crosstalk between microRNA and DNA Methylation Offers Potential Biomarkers and Targeted Therapies in ALK-Positive Lymphomas
tto The discovery of microRNA (miRNA) has provided new and powerful tools for studying the mechanism, diagnosis and treatment of human cancers. The down-regulation of tumor suppressive miRNA by hypermethylation of CpG island (CpG is shorthand for 5′-C-phosphate-G-3′, that is, cytosine and guanine separated by only one phosphate) is emerging as a common hallmark of cancer and appears to be involved in drug resistance. This review discusses the role of miRNA and DNA methylation in drug resistance mechanisms and highlights their potential as anti-cancer therapies in Anaplastic Lymphoma Kinase (ALK)-positive ly...
Source: Cancers - August 3, 2017 Category: Cancer & Oncology Authors: Coralie Hoareau-Aveilla Fabienne Meggetto Tags: Review Source Type: research

Cancers, Vol. 9, Pages 101: Epithelial-to-Mesenchymal Transition and MicroRNAs in Lung Cancer
es Pierre Laurent-Puig Hélène Blons Despite major advances, non-small cell lung cancer (NSCLC) remains the major cause of cancer-related death in developed countries. Metastasis and drug resistance are the main factors contributing to relapse and death. Epithelial-to-mesenchymal transition (EMT) is a complex molecular and cellular process involved in tissue remodelling that was extensively studied as an actor of tumour progression, metastasis and drug resistance in many cancer types and in lung cancers. Here we described with an emphasis on NSCLC how the changes in signalling pathways, transcription f...
Source: Cancers - August 3, 2017 Category: Cancer & Oncology Authors: Antoine Legras Nicolas P écuchet Sandrine Imbeaud Karine Pallier Audrey Didelot H élène Roussel Laure Gibault Elizabeth Fabre Fran çoise Le Pimpec-Barthes Pierre Laurent-Puig H élène Blons Tags: Review Source Type: research

Cancers, Vol. 9, Pages 99: Performance of a RT-PCR Assay in Comparison to FISH and Immunohistochemistry for the Detection of ALK in Non-Small Cell Lung Cancer
In this study, we performed a direct comparison of formalin-fixed paraffin-embedded (FFPE) lung cancer specimens using all three ALK detection methods. The RT-PCR test (diagnostic cut-off ΔCt of ≤8) was shown to be highly sensitive (100%) when compared to FISH and IHC. Sequencing of RNA detected full-length ALK transcripts or EML4-ALK and KIF5B-ALK fusion variants in discordant cases in which ALK expression was detected by the ALK RT-PCR test but negative by FISH and IHC. The overall specificity of the RT-PCR test for the detection of ALK in cases without full-length ALK expression was 94% in comparison to FISH an...
Source: Cancers - August 1, 2017 Category: Cancer & Oncology Authors: David Hout Brock Schweitzer Kasey Lawrence Stephan Morris Tracy Tucker Rosetta Mazzola Rachel Skelton Frank McMahon John Handshoe Mary Lesperance Aly Karsan David Saltman Tags: Article Source Type: research

Cancers, Vol. 9, Pages 98: EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang Equilibrium Recapitulated in Cell Spheroids
Elisa Messina The epithelial-to-mesenchymal transition (EMT) is an essential trans-differentiation process, which plays a critical role in embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. It is the fundamental mechanism by which epithelial cells lose many of their characteristics while acquiring features typical of mesenchymal cells, such as migratory capacity and invasiveness. Depending on the contest, EMT is complemented and balanced by the reverse process, the mesenchymal-to-epithelial transition (MET). In the saving economy of the living organisms, the same (Ying-...
Source: Cancers - July 29, 2017 Category: Cancer & Oncology Authors: Elvira Forte Isotta Chimenti Paolo Rosa Francesco Angelini Francesca Pagano Antonella Calogero Alessandro Giacomello Elisa Messina Tags: Review Source Type: research

Cancers, Vol. 9, Pages 97: Localization of VEGF to Vascular ECM Is an Important Aspect of Tumor Angiogenesis
cup Our research has identified several examples in which reduced VEGF-A binding to deficient vascular extracellular matrix leads to deficits in tumor vascularization and tumor growth: (1) germline ablation of collagen VI in the stroma of intracranial B16F10 melanomas; (2) knockdown of the Tks5 scaffolding protein in MDA-MB-231 mammary tumor cells; (3) germline ablation of NG2 proteoglycan in the stroma of MMTV-PyMT mammary tumors; and (4) myeloid-specific ablation of NG2 in the stroma of intracranial B16F10 melanomas. Tumor hypoxia is increased in each of the four types of experimental mice, accompanied by increases i...
Source: Cancers - July 28, 2017 Category: Cancer & Oncology Authors: Weon-Kyoo You William Stallcup Tags: Commentary Source Type: research

Cancers, Vol. 9, Pages 95: Integrins and Exosomes, a Dangerous Liaison in Cancer Progression
lli Integrin activity and function is classically related to the bi-directional regulation of cell-extracellular matrix (ECM) contacts that regulate a number of cell pathways linked to cell adhesion, cell detachment from ECM, cell migration, and anoikis. Interestingly, emerging data continue to uncover new roles for integrins in cancer-relevant pathways, particularly concerning the regulation of immune cell activity in the tumor niche, like myeloid cell differentiation and function and, very recently, the regulation of metastatic processes by exosomes. Exosomes are deeply involved in cell-cell communication processes a...
Source: Cancers - July 26, 2017 Category: Cancer & Oncology Authors: Mayra Paolillo Sergio Schinelli Tags: Review Source Type: research

Cancers, Vol. 9, Pages 96: Involvement of the Integrin α1β1 in the Progression of Colorectal Cancer
Cancers, Vol. 9, Pages 96: Involvement of the Integrin α1β1 in the Progression of Colorectal Cancer Cancers doi: 10.3390/cancers9080096 Authors: Salah Boudjadi Gérald Bernatchez Blanche Sénicourt Marco Beauséjour Pierre Vachon Julie Carrier Jean-François Beaulieu Integrins are a family of heterodimeric glycoproteins involved in bidirectional cell signaling that participate in the regulation of cell shape, adhesion, migration, survival and proliferation. The integrin α1β1 is known to be involved in RAS/ERK proliferative pathway activation and plays an imp...
Source: Cancers - July 26, 2017 Category: Cancer & Oncology Authors: Salah Boudjadi G érald Bernatchez Blanche S énicourt Marco Beaus éjour Pierre Vachon Julie Carrier Jean-Fran çois Beaulieu Tags: Article Source Type: research

Cancers, Vol. 9, Pages 94: Targeting Platelets for the Treatment of Cancer
etharom The majority of cancer-associated mortality results from the ability of tumour cells to metastasise leading to multifunctional organ failure and death. Disseminated tumour cells in the blood circulation are faced with major challenges such as rheological shear stresses and cell-mediated cytotoxicity mediated by natural killer cells. Nevertheless, circulating tumour cells with metastatic ability appear equipped to exploit host cells to aid their survival. Despite the long interest in targeting tumour-associated host cells such as platelets for cancer treatment, the clinical benefit of this strategy is still unde...
Source: Cancers - July 22, 2017 Category: Cancer & Oncology Authors: Omar Elaskalani Michael Berndt Marco Falasca Pat Metharom Tags: Review Source Type: research

Cancers, Vol. 9, Pages 93: Seed-in-Soil: Pancreatic Cancer Influenced by Tumor Microenvironment
Lin Pancreatic ductal adenocarcinoma is a fatal malignancy with a five-year survival rate lower than 7%, and most patients dying within six months of diagnosis. The factors that contribute to the aggressiveness of the disease include, but are not limited to: late diagnosis, prompt metastasis to adjacent vital organs, poor response, and resistance to anticancer treatments. This malignancy is uniquely associated with desmoplastic stroma that accounts for 80% of tumor mass. Understanding the biology of stroma can aid the discovery of innovative strategies for eradicating this lethal cancer in the future. This review highl...
Source: Cancers - July 21, 2017 Category: Cancer & Oncology Authors: Huey-Jen Lin Jiayuh Lin Tags: Review Source Type: research

Cancers, Vol. 9, Pages 92: Regional Delivery of Chimeric Antigen Receptor (CAR) T-Cells for Cancer Therapy
cca Chimeric Antigen Receptor (CAR) T-cells are T-cells with recombinant receptors targeted to tumor antigens. CAR-T cell therapy has emerged as a mode of immunotherapy and is now being extensively explored in hematologic cancer. In contrast, CAR-T cell use in solid tumors has been hampered by multiple obstacles. Several approaches have been taken to circumvent these obstacles, including the regional delivery of CAR-T cells. Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery. We reviewe...
Source: Cancers - July 18, 2017 Category: Cancer & Oncology Authors: Praveen Sridhar Fabio Petrocca Tags: Review Source Type: research

Cancers, Vol. 9, Pages 91: Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis
ros Georgakilas Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of ...
Source: Cancers - July 18, 2017 Category: Cancer & Oncology Authors: Ifigeneia Mavragani Zacharenia Nikitaki Maria Souli Asef Aziz Somaira Nowsheen Khaled Aziz Emmy Rogakou Alexandros Georgakilas Tags: Review Source Type: research

Cancers, Vol. 9, Pages 89: The Role of Radiation Induced Injury on Lung Cancer
This manuscript evaluates the role of cell killing, tissue disorganization, and tissue damage on the induction of lung cancer following low dose rate radiation exposures from internally deposited radioactive materials. Beagle dogs were exposed by inhalation to 90Y, 91Y, 144Ce, or 90Sr in fused clay particles. Dogs lived out their life span with complete pathology conducted at the time of death. The radiation dose per cell turnover was characterized and related to the cause of death for each animal. Large doses per cell turnover resulted in acute death from lung damage with extensive cell killing, tissue disorganization, ch...
Source: Cancers - July 12, 2017 Category: Cancer & Oncology Authors: Stephanie Puukila Christopher Thome Antone Brooks Gayle Woloschak Douglas Boreham Tags: Article Source Type: research

Cancers, Vol. 9, Pages 90: SIRT3: Oncogene and Tumor Suppressor in Cancer
Sirtuin 3 (SIRT3), the major deacetylase in mitochondria, plays a crucial role in modulating oxygen reactive species (ROS) and limiting the oxidative damage in cellular components. SIRT3 targets different enzymes which regulate mitochondrial metabolism and participate in ROS detoxification, such as the complexes of the respiratory chain, the isocitrate dehydrogenase, or the manganese superoxide dismutase. Thus, SIRT3 activity is essential in maintaining mitochondria homeostasis and has recently received great attention, as it is considered a fidelity protein for mitochondrial function. In some types of cancer, SIRT3 functi...
Source: Cancers - July 12, 2017 Category: Cancer & Oncology Authors: Margalida Torrens-Mas Jordi Oliver Pilar Roca Jorge Sastre-Serra Tags: Review Source Type: research

Cancers, Vol. 9, Pages 87: Role and Therapeutic Targeting of the HGF/MET Pathway in Glioblastoma
Glioblastoma (GBM) is a lethal brain tumor with dismal prognosis. Current therapeutic options, consisting of surgery, chemotherapy and radiation, have only served to marginally increase patient survival. Receptor tyrosine kinases (RTKs) are dysregulated in approximately 90% of GBM; attributed to this, research has focused on inhibiting RTKs as a novel and effective therapy for GBM. Overexpression of RTK mesenchymal epithelial transition (MET), and its ligand, hepatocyte growth factor (HGF), in GBM highlights a promising new therapeutic target. This review will discuss the role of MET in cell cycle regulation, cell prolifer...
Source: Cancers - July 11, 2017 Category: Cancer & Oncology Authors: Nichola Cruickshanks Ying Zhang Fang Yuan Mary Pahuski Myron Gibert Roger Abounader Tags: Review Source Type: research

Cancers, Vol. 9, Pages 88: Cost Saving Opportunities in NSCLC Therapy by Optimized Diagnostics
With an incidence of 68 new cases per 100,000 people per year, an estimated total number of up to 350,000 new non-small-cell lung cancer (NSCLC) cases are diagnosed each year in the European Union. Up to 10% of NSCLC patients are eligible for therapy with novel ALK (anaplastic lymphoma kinase) inhibitors, as they have been diagnosed with a mutation in the gene coding for ALK. The ALK inhibitor therapy costs add up to approx. 9,000 € per patient per month, with treatment durations of up to one year. Recent studies have shown that up to 10% of ALK cases are misdiagnosed by nearly 40% of pathologic investigations. The cu...
Source: Cancers - July 11, 2017 Category: Cancer & Oncology Authors: Ilija Nenadi ć Jeanine Staber Susanne Dreier Guus Simons Verena Schildgen Michael Brockmann Oliver Schildgen Tags: Opinion Source Type: research

Cancers, Vol. 9, Pages 86: Phosphoinositide 3-Kinase-Dependent Signalling Pathways in Cutaneous Squamous Cell Carcinomas
Cutaneous squamous cell carcinoma (cSCC) derives from keratinocytes in the epidermis and accounts for 15 –20% of all cutaneous malignancies. Although it is usually curable by surgery, 5% of these tumours metastasise leading to poor prognosis mostly because of a lack of therapies and validated biomarkers. As the incidence rate is rising worldwide it has become increasingly important to better understa nd the mechanisms involved in cSCC development and progression in order to develop therapeutic strategies. Here we discuss some of the evidence indicating that activation of phosphoinositide 3-kinases (PI3Ks)-dependent s...
Source: Cancers - July 11, 2017 Category: Cancer & Oncology Authors: Joanna Janus Ryan O ’Shaughnessy Catherine Harwood Tania Maffucci Tags: Review Source Type: research

Cancers, Vol. 9, Pages 85: The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas
MicroRNAs (miRNAs) are small, non-coding, endogenous RNA molecules that function in gene silencing by post-transcriptional regulation of gene expression. The dysregulation of miRNA plays a pivotal role in cancer tumorigenesis, including the development and progression of gliomas. Their small size, stability and ability to target multiple oncogenes have simultaneously distinguished miRNAs as attractive candidates for biomarkers and novel therapeutic targets for glioma patients. In this review, we summarize the most frequently cited miRNAs known to contribute to gliomagenesis and progression by regulating the defining hallma...
Source: Cancers - July 10, 2017 Category: Cancer & Oncology Authors: Sasha Beyer Jessica Fleming Wei Meng Rajbir Singh S. Haque Arnab Chakravarti Tags: Review Source Type: research

Cancers, Vol. 9, Pages 84: Integrin αvβ3 Signaling in Tumor-Induced Bone Disease
Tumor-induced bone disease is common among patients with advanced solid cancers, especially those with breast, prostate, and lung malignancies. The tendency of these cancers to metastasize to bone and induce bone destruction is, in part, due to alterations in integrin expression and signaling. Substantial evidence from preclinical studies shows that increased expression of integrin αvβ3 in tumor cells promotes the metastatic and bone-invasive phenotype. Integrin αvβ3 mediates cell adhesion to several extracellular matrix proteins in the bone microenvironment which is necessary for tumor cell colonizat...
Source: Cancers - July 8, 2017 Category: Cancer & Oncology Authors: Kristin Kwakwa Julie Sterling Tags: Review Source Type: research

Cancers, Vol. 9, Pages 83: Potential of Integrin Inhibitors for Treating Ovarian Cancer: A Literature Review
Epithelial ovarian cancer is a fatal disease, with a cure rate of only 30%. Several recent studies have targeted integrins for cancer treatment. Preclinical studies have shown the effectiveness of several integrin inhibitors for blocking cancer progression, especially by blocking angiogenesis. Because the initial critical step in ovarian cancer metastasis is the attachment of cancer cells to the peritoneum or omentum and because clinical trials have provided positive results for anti-angiogenic therapy, therapies targeting integrins may be the most feasible approach for treating cancer. This review summarizes the current u...
Source: Cancers - July 8, 2017 Category: Cancer & Oncology Authors: Masaki Kobayashi Kenjiro Sawada Tadashi Kimura Tags: Review Source Type: research

Cancers, Vol. 9, Pages 81: The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer
DNA double-strand breaks (DSBs) are deleterious DNA lesions that if left unrepaired or are misrepaired, potentially result in chromosomal aberrations, known drivers of carcinogenesis. Pathways that direct the repair of DSBs are traditionally believed to be guardians of the genome as they protect cells from genomic instability. The prominent DSB repair pathway in human cells is the non-homologous end joining (NHEJ) pathway, which mediates template-independent re-ligation of the broken DNA molecule and is active in all phases of the cell cycle. Its role as a guardian of the genome is supported by the fact that defects in NHE...
Source: Cancers - July 6, 2017 Category: Cancer & Oncology Authors: Brock Sishc Anthony Davis Tags: Review Source Type: research

Cancers, Vol. 9, Pages 82: Inside the Cell: Integrins as New Governors of Nuclear Alterations?
Cancer cell migration is a complex process that requires coordinated structural changes and signals in multiple cellular compartments. The nucleus is the biggest and stiffest organelle of the cell and might alter its physical properties to allow cancer cell movement. Integrins are transmembrane receptors that mediate cell-cell and cell-extracellular matrix interactions, which regulate numerous intracellular signals and biological functions under physiological conditions. Moreover, integrins orchestrate changes in tumor cells and their microenvironment that lead to cancer growth, survival and invasiveness. Most of the resea...
Source: Cancers - July 6, 2017 Category: Cancer & Oncology Authors: Elena Madrazo Andrea Cordero Conde Javier Redondo-Mu ñoz Tags: Review Source Type: research

Cancers, Vol. 9, Pages 78: Can Integrin Agonists Have Cards to Play against Cancer? A Literature Survey of Small Molecules Integrin Activators
The ability of integrins to activate and integrate intracellular communication illustrates the potential of these receptors to serve as functional distribution hubs in a bi-directional signal transfer outside-in and inside-out of the cells. Tight regulation of the integrin signaling is paramount for normal physiological functions such as migration, proliferation, and differentiation, and misregulated integrin activity could be associated with several pathological conditions. Because of the important roles of integrins and their ligands in biological development, immune responses, leukocyte traffic, haemostasis, and cancer,...
Source: Cancers - July 5, 2017 Category: Cancer & Oncology Authors: Alessandra Tolomelli Paola Galletti Monica Baiula Daria Giacomini Tags: Review Source Type: research

Cancers, Vol. 9, Pages 80: Erratum: Tanaka, T. et al. Cimetidine and Clobenpropit Attenuate Inflammation-Associated Colorectal Carcinogenesis in Male ICR Mice. Cancers, 2016, 8, 25
n/a (Source: Cancers)
Source: Cancers - July 5, 2017 Category: Cancer & Oncology Authors: Takuji Tanaka Takahiro Kochi Yohei Shirakami Takayuki Mori Ayumi Niwa Naoki Watanabe Hisataka Moriwaki Masahito Shimizu Tags: Erratum Source Type: research

Cancers, Vol. 9, Pages 79: Roles of Integrin α6β4 Glycosylation in Cancer
Malignant transformation is accompanied with aberrant glycosylation of proteins. Such changes in glycan structure also occur in the integrins, which are a large family of cell surface receptors for the extracellular matrix and play key roles in tumor progression. There is now increasing evidence that glycosylation of integrins affects cellular signaling and interaction with the extracellular matrix, receptor tyrosine kinases, and galectins, thereby regulating cell adhesion, motility, growth, and survival. Integrin α6β4 is a receptor for laminin-332 and the increased expression level is correlated with malignant ...
Source: Cancers - July 5, 2017 Category: Cancer & Oncology Authors: Yoshinobu Kariya Yukiko Kariya Jianguo Gu Tags: Review Source Type: research

Cancers, Vol. 9, Pages 77: Epithelial-to-Pericyte Transition in Cancer
During epithelial-to-mesenchymal transition (EMT), cells lose epithelial characteristics and acquire mesenchymal properties. These two processes are genetically separable and governed by distinct transcriptional programs, rendering the EMT outputs highly heterogeneous. Our recent study shows that the mesenchymal products generated by EMT often express multiple pericyte markers, associate with and stabilize blood vessels to fuel tumor growth, thus phenotypically and functionally resembling pericytes. Therefore, some EMT events represent epithelial-to-pericyte transition (EPT). The serum response factor (SRF) plays key roles...
Source: Cancers - July 4, 2017 Category: Cancer & Oncology Authors: Jianrong Lu Anitha Shenoy Tags: Review Source Type: research

Cancers, Vol. 9, Pages 76: Epithelial-to-Mesenchymal Transition in the Pathogenesis and Therapy of Head and Neck Cancer
Head and neck cancer (HNC) is one of the most prevalent human malignancies worldwide, with a high morbidity and mortality. Implementation of interdisciplinary treatment modalities has improved the quality of life, but only minor changes in overall survival have been achieved over the past decades. Main causes for treatment failure are an aggressive and invasive tumor growth in combination with a high degree of intrinsic or acquired treatment resistance. A subset of tumor cells gain these properties during malignant progression by reactivating a complex program of epithelia-to-mesenchymal transition (EMT), which is integral...
Source: Cancers - July 3, 2017 Category: Cancer & Oncology Authors: Julia Thierauf Johannes Veit Jochen Hess Tags: Review Source Type: research

Cancers, Vol. 9, Pages 75: Pleiotropic Roles of Non-Coding RNAs in TGF- β-Mediated Epithelial-Mesenchymal Transition and Their Functions in Tumor Progression
Cancers, Vol. 9, Pages 75: Pleiotropic Roles of Non-Coding RNAs in TGF-β-Mediated Epithelial-Mesenchymal Transition and Their Functions in Tumor Progression Cancers doi: 10.3390/cancers9070075 Authors: Simon Grelet Ariel McShane Renaud Geslain Philip H. Howe Epithelial-mesenchymal transition (EMT) is a spatially- and temporally-regulated process involved in physiological and pathological transformations, such as embryonic development and tumor progression. While the role of TGF-β as an EMT-inducer has been extensively documented, the molecular mechanisms regulating this transition and their implicat...
Source: Cancers - July 1, 2017 Category: Cancer & Oncology Authors: Simon Grelet Ariel McShane Renaud Geslain Philip H. Howe Tags: Review Source Type: research

Cancers, Vol. 9, Pages 75: Pleiotropic Roles of Non-Coding RNAs in TGF-β-Mediated Epithelial-Mesenchymal Transition and Their Functions in Tumor Progression
Epithelial-mesenchymal transition (EMT) is a spatially- and temporally-regulated process involved in physiological and pathological transformations, such as embryonic development and tumor progression. While the role of TGF- β as an EMT-inducer has been extensively documented, the molecular mechanisms regulating this transition and their implications in tumor metastasis are still subjects of intensive debates and investigations. TGF-β regulates EMT through both transcriptional and post-transcriptional mechanisms, and recent advances underline the critical roles of non-coding RNAs in these processes. Although micr...
Source: Cancers - July 1, 2017 Category: Cancer & Oncology Authors: Simon Grelet Ariel McShane Renaud Geslain Philip H. Howe Tags: Review Source Type: research

Cancers, Vol. 9, Pages 74: Specific Depletion of Leukemic Stem Cells: Can MicroRNAs Make the Difference?
For over 40 years the standard treatment for acute myeloid leukemia (AML) patients has been a combination of chemotherapy consisting of cytarabine and an anthracycline such as daunorubicin. This standard treatment results in complete remission (CR) in the majority of AML patients. However, despite these high CR rates, only 30 –40% (<60 years) and 10 –20% (>60 years) of patients survive five years after diagnosis. The main cause of this treatment failure is insufficient eradication of a subpopulation of chemotherapy resistant leukemic cells with stem cell-like properties, often referred to as &ldqu...
Source: Cancers - June 30, 2017 Category: Cancer & Oncology Authors: Tania Marti áñez Canales David de Leeuw Eline Vermue Gert Ossenkoppele Linda Smit Tags: Review Source Type: research

Cancers, Vol. 9, Pages 73: Quality-of-Life (QOL) during Screening for Phase 1 Trial Studies in Patients with Advanced Solid Tumors and Its Impact on Risk for Serious Adverse Events
Conclusions: Lower (worse) EORTC QLQ-C30 score at baseline is associated with SAE occurrence during phase 1 oncology trials. (Source: Cancers)
Source: Cancers - June 26, 2017 Category: Cancer & Oncology Authors: Sidra Anwar Wei Tan Chi-Chen Hong Sonal Admane Askia Dozier Francine Siedlecki Amy Whitworth Ann Marie DiRaddo Dawn DePaolo Sandra M. Jacob Wen Wee Ma Austin Miller Alex A. Adjei Grace K. Dy Tags: Article Source Type: research

Cancers, Vol. 9, Pages 71: Exosomal MicroRNAs in Breast Cancer towards Diagnostic and Therapeutic Applications
Soon after the discovery of microRNAs over 15 years ago, a myriad of research groups around the world sought to develop clinical applications in breast cancer for these short, noncoding, regulatory RNAs. While little of this knowledge has translated into the clinic, the recent research explosion on cell-to-cell communication via exosomes and other extracellular vesicles has rekindled interest in microRNA-based clinical applications. microRNAs appear to be a preferential and important cargo of exosomes in mediating biological effects in recipient cells. This review highlights recent studies on the biology of exosomal microR...
Source: Cancers - June 24, 2017 Category: Cancer & Oncology Authors: Lorenzo Sempere Jessica Keto Muller Fabbri Tags: Review Source Type: research

Cancers, Vol. 9, Pages 72: Epigenetic Regulation of the Epithelial to Mesenchymal Transition in Lung Cancer
Lung cancer is the leading cause of cancer deaths worldwide. It is an aggressive and devastating cancer because of metastasis triggered by enhanced migration and invasion, and resistance to cytotoxic chemotherapy. The epithelial to mesenchymal transition (EMT) is a fundamental developmental process that is reactivated in wound healing and a variety of diseases including cancer where it promotes migration/invasion and metastasis, resistance to treatment, and generation and maintenance of cancer stem cells. The induction of EMT is associated with reprogramming of the epigenome. This review focuses on major mechanisms of epig...
Source: Cancers - June 24, 2017 Category: Cancer & Oncology Authors: Jo ëlle Roche Robert Gemmill Harry Drabkin Tags: Review Source Type: research

Cancers, Vol. 9, Pages 70: Phenotypic Plasticity and Cell Fate Decisions in Cancer: Insights from Dynamical Systems Theory
Waddington ’s epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of “landscape” in the context of dynamical systems theory represents a high-dimensional space, in which each cell phen otype is considered as an “attractor” that is determined by interactions between multiple molecular players, and is buffered against environmental fluctuations. In addition, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions ...
Source: Cancers - June 22, 2017 Category: Cancer & Oncology Authors: Dongya Jia Mohit Kumar Jolly Prakash Kulkarni Herbert Levine Tags: Review Source Type: research

Cancers, Vol. 9, Pages 69: Selection of Nucleic Acid Aptamers Targeting Tumor Cell-Surface Protein Biomarkers
Aptamers are nucleic acids referred to as chemical antibodies as they bind to their specific targets with high affinity and selectivity. They are selected via an iterative process known as ‘selective evolution of ligands by exponential enrichment’ (SELEX). Aptamers have been developed against numerous cancer targets and among them, many tumor cell-membrane protein biomarkers. The identification of aptamers targeting cell-surface proteins has mainly been performed by two different strategies: protein- and cell-based SELEX, when the targets used for selection were proteins and cells, respectively. This review aim...
Source: Cancers - June 21, 2017 Category: Cancer & Oncology Authors: Marie-C écile Mercier Monique Dontenwill Laurence Choulier Tags: Review Source Type: research

Cancers, Vol. 9, Pages 68: Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling
Macrophages interact with cells in every organ to facilitate tissue development, function and repair. However, the close interaction between macrophages and parenchymal cells can be subverted in disease, particularly cancer. Motility is an essential capacity for macrophages to be able to carry out their various roles. In cancers, the macrophage ’s interstitial migratory ability is frequently co-opted by tumor cells to enable escape from the primary tumor and metastatic spread. Macrophage accumulation within and movement through a tumor is often stimulated by tumor cell production of the mononuclear phagocytic growth ...
Source: Cancers - June 18, 2017 Category: Cancer & Oncology Authors: Amy Dwyer Eloise Greenland Fiona Pixley Tags: Review Source Type: research

Cancers, Vol. 9, Pages 67: Androgen Receptor-Dependent and -Independent Mechanisms Involved in Prostate Cancer Therapy Resistance
Despite the initial efficacy of androgen deprivation in prostate cancer, virtually all patients progress to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling is critically required for CRPC. A new generation of medications targeting AR, such as abiraterone and enzalutamide, has improved survival of metastatic CRPC (mCRPC) patients. However, a significant proportion of patients presents with primary resistance to these agents, and in the remainder, secondary resistance will invariably develop, which makes mCRPC the lethal form of the disease. Mechanisms underlying progression to mCRPC and treatme...
Source: Cancers - June 12, 2017 Category: Cancer & Oncology Authors: Daniel Crona Young Whang Tags: Review Source Type: research

Cancers, Vol. 9, Pages 66: Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair
Compared to conventional photon-based external beam radiation (PhXRT), carbon ion radiotherapy (CIRT) has superior dose distribution, higher linear energy transfer (LET), and a higher relative biological effectiveness (RBE). This enhanced RBE is driven by a unique DNA damage signature characterized by clustered lesions that overwhelm the DNA repair capacity of malignant cells. These physical and radiobiological characteristics imbue heavy ions with potent tumoricidal capacity, while having the potential for simultaneously maximally sparing normal tissues. Thus, CIRT could potentially be used to treat some of the most diffi...
Source: Cancers - June 9, 2017 Category: Cancer & Oncology Authors: Osama Mohamad Brock Sishc Janapriya Saha Arnold Pompos Asal Rahimi Michael Story Anthony Davis D.W. Kim Tags: Review Source Type: research

Cancers, Vol. 9, Pages 65: Bridging Plant and Human Radiation Response and DNA Repair through an In Silico Approach
In this study, we have applied an innovative approach utilizing data pertinent to plant and human genes from publicly available databases towards the design of a ‘plant radiation biodosimeter’, that is, a plant and DDR gene-based platform that could serve as a REM reliable biomarker for assessing environmental radiation exposure and associated risk. From our analysis, in addition to REM biomarkers, a significant number of genes, both in human and Arabido psis thaliana, not yet characterized as DDR, are suggested as possible DNA repair players. Last but not least, we provide an example on the applicability of an...
Source: Cancers - June 6, 2017 Category: Cancer & Oncology Authors: Zacharenia Nikitaki Athanasia Pavlopoulou Marcela Hol á Mattia Don à Ioannis Michalopoulos Alma Balestrazzi Karel Angelis Alexandros Georgakilas Tags: Article Source Type: research

Cancers, Vol. 9, Pages 63: Combination of Near Infrared Light-Activated Photodynamic Therapy Mediated by Indocyanine Green with Etoposide to Treat Non-Small-Cell Lung Cancer
This study therefore shows the anticancer efficacy of ICG-PDT combined with VP-16. These findings suggest that ICG-mediated PDT may be applied in combination with the chemotherapy drug VP-16 to treat some cancers, especially the non-small-cell lung cancer. (Source: Cancers)
Source: Cancers - June 5, 2017 Category: Cancer & Oncology Authors: Ting Luo Qinrong Zhang Qing-Bin Lu Tags: Article Source Type: research

Cancers, Vol. 9, Pages 64: Being-in-the-Chemotherapy-Suite versus Being-in-the-Oncology-Ward: An Analytical View of Two Hospital Sites Occupied by People Experiencing Cancer
This article reports on findings that have emerged from ongoing analysis that has been completed in the years proceeding data collection. An ethnographic research design was used to collect data about the participants and th eir family members over a three-year period. Data was collected using participant observation and semi-structured interviews. Over 380 transcripts based on field note entries and taped interviews were produced during the 1121 h of contact with participants and family members that made up the researc h period. Analysis of these texts identified two focal sites within Christchurch Hospital that were occu...
Source: Cancers - June 5, 2017 Category: Cancer & Oncology Authors: Catherine Hughes Kate Heugten Sally Keeling Francisc Szekely Tags: Article Source Type: research

Cancers, Vol. 9, Pages 62: Local Immune Responsiveness of Mice Bearing Premalignant Oral Lesions to PD-1 Antibody Treatment
A carcinogen-induced premalignant oral lesion model that progresses to oral cancer was used to examine the immunological impact of a 5-week treatment regimen to block programmed cell death protein 1 (PD-1). PD-1 antibody treatment resulted in concurrent, but transient, increases in interleukin (IL)-2, IFN- γ and IL-17, and delayed increases in IL-6 and IL-10 within the lesion-bearing tongue epithelium. In contrast, cytokine secretion by lymph node cells of PD-1 antibody-treated mice was lower than for mice treated with control antibodies, with the exception of interferon (IFN)-γ, whose secretion inc reased late...
Source: Cancers - June 2, 2017 Category: Cancer & Oncology Authors: Corinne Levingston M. Young Tags: Article Source Type: research