Cancers, Vol. 11, Pages 553: MicroRNA-Based Diagnosis and Treatment of Metastatic Human Osteosarcoma
Okada Osteosarcoma is a malignant tumor of the bones that commonly occurs in young individuals. The 5-year survival rate of osteosarcoma patients is 60–70%. Metastasis to the lungs leads to death in 30–40% of osteosarcoma patients. Therefore, the development of effective strategies for early detection and treatment of this disease are important to improve the survival of osteosarcoma patients. However, metastatic markers for osteosarcoma and molecules that might be targeted for the treatment of metastatic osteosarcoma have not been identified yet. Therefore, the mechanism of metastasis to th...
Source: Cancers - April 18, 2019 Category: Cancer & Oncology Authors: Ryo Sasaki Mitsuhiko Osaki Futoshi Okada Tags: Review Source Type: research

Cancers, Vol. 11, Pages 555: Targeting Wnt Signaling via Notch in Intestinal Carcinogenesis
s Gassler Proliferation and differentiation of intestinal epithelial cells is assisted by highly specialized and well-regulated signaling cascades. The Wnt pathway, which is one of the fundamental pathways in the intestine, contributes to the organization of proliferative intestinal crypts by positioning and cycling of intestinal stem cells and their derivatives. The Wnt pathway promotes differentiation of intestinal secretory cell types along the crypt-plateau and crypt-villus axis. In contrast to the Wnt pathway, the intestinal Notch cascade participates in cellular differentiation and directs progenitor cells toward...
Source: Cancers - April 18, 2019 Category: Cancer & Oncology Authors: Elke Kaemmerer Min Kyung Jeon Alexander Berndt Christian Liedtke Nikolaus Gassler Tags: Review Source Type: research

Cancers, Vol. 11, Pages 556: Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer
n Michael Blank SMURF2, an E3 ubiquitin ligase and suggested tumor suppressor, operates in normal cells to prevent genomic instability and carcinogenesis. However, the mechanisms underlying SMURF2 inactivation in human malignancies remain elusive, as SMURF2 is rarely found mutated or deleted in cancers. We hypothesized that SMURF2 might have a distinct molecular biodistribution in cancer versus normal cells and tissues. The expression and localization of SMURF2 were analyzed in 666 human normal and cancer tissues, with primary focus on prostate and breast tumors. These investigations were accompanied by SMURF2 gene e...
Source: Cancers - April 18, 2019 Category: Cancer & Oncology Authors: Andrea Emanuelli Dhanoop Manikoth Ayyathan Praveen Koganti Pooja Anil Shah Liat Apel-Sarid Biagio Paolini Rajesh Detroja Milana Frenkel-Morgenstern Michael Blank Tags: Article Source Type: research

Cancers, Vol. 11, Pages 554: Complementary Roles of GCN5 and PCAF in Foxp3+ T-Regulatory Cells
Wayne W. Hancock Functions of the GCN5-related N-acetyltransferase (GNAT) family of histone/protein acetyltransferases (HATs) in Foxp3+ T-regulatory (Treg) cells are unexplored, despite the general importance of these enzymes in cell biology. We now show that two prototypical GNAT family members, GCN5 (general control nonrepressed-protein 5, lysine acetyltransferase (KAT)2a) and p300/CBP-associated factor (p300/CBP-associated factor (PCAF), Kat2b) contribute to Treg functions through partially distinct and partially overlapping mechanisms. Deletion of Gcn5 or PCAF did not affect Treg development or suppressive functio...
Source: Cancers - April 18, 2019 Category: Cancer & Oncology Authors: Yujie Liu Chunrong Bao Liqing Wang Rongxiang Han Ulf H. Beier Tatiana Akimova Philip A. Cole Sharon Y. R. Dent Wayne W. Hancock Tags: Article Source Type: research

Cancers, Vol. 11, Pages 557: DIRAS3-Derived Peptide Inhibits Autophagy in Ovarian Cancer Cells by Binding to Beclin1
Kim Zhen Lu Robert C. Bast Autophagy can protect cancer cells from acute starvation and enhance resistance to chemotherapy. Previously, we reported that autophagy plays a critical role in the survival of dormant, drug resistant ovarian cancer cells using human xenograft models and correlated the up-regulation of autophagy and DIRAS3 expression in clinical samples obtained during “second look” operations. DIRAS3 is an imprinted tumor suppressor gene that encodes a 26 kD GTPase with homology to RAS that inhibits cancer cell proliferation and motility. Re-expression of DIRAS3 in ovarian ca...
Source: Cancers - April 18, 2019 Category: Cancer & Oncology Authors: Margie N. Sutton Gilbert Y. Huang Xiaowen Liang Rajesh Sharma Albert S. Reger Weiqun Mao Lan Pang Philip J. Rask Kwangkook Lee Joshua P. Gray Amy M. Hurwitz Timothy Palzkill Steven W. Millward Choel Kim Zhen Lu Robert C. Bast Tags: Article Source Type: research

Cancers, Vol. 11, Pages 558: TRPC3 Regulates the Proliferation and Apoptosis Resistance of Triple Negative Breast Cancer Cells through the TRPC3/RASA4/MAPK Pathway
In this study, subcellular fractionation followed by Western blot and immunocytochemistry showed that TRPC3 was over-expressed on the plasma membrane of TNBC line MDA-MB-231 when compared to an estrogen receptor-positive cell line MCF-7. TRPC3 blocker Pyr3 and dominant negative of TRPC3 attenuated proliferation, induced apoptosis and sensitized cell death to chemotherapeutic agents in MDA-MB-231 as measured by proliferation assays. Interestingly, Ras GTPase-activating protein 4 (RASA4), a Ca2+-promoted Ras-MAPK pathway suppressor, was found to be located on the plasma membrane of MDA-MB-231. Blocking TRPC3 decreased the am...
Source: Cancers - April 18, 2019 Category: Cancer & Oncology Authors: Wang Qi Qi Tsang Tags: Article Source Type: research

Cancers, Vol. 11, Pages 559: New Insights into the Implication of Epigenetic Alterations in the EMT of Triple Negative Breast Cancer
idet Breast cancer is the most common cancer and leading cause of cancer death among women worldwide, encompassing a wide heterogeneity of subtypes with different clinical features. During the last two decades, the use of targeted therapies has emerged in clinical research in order to increase treatment efficiency, improve prognosis and reduce recurrence. However, the triple negative breast cancer (TNBC) subtype remains a clinical challenge, with poor prognosis since no therapeutic targets have been identified. This aggressive breast cancer entity lacks expression of oestrogen receptor (ER) and progesterone receptor (P...
Source: Cancers - April 18, 2019 Category: Cancer & Oncology Authors: Khaled Bidet Tags: Review Source Type: research

Cancers, Vol. 11, Pages 550: Timing of Adjuvant Chemotherapy and Survival in Colorectal, Gastric, and Pancreatic Cancer. A Systematic Review and Meta-Analysis
Conclusions: Starting adjuvant CT within 6–8 weeks post-surgery is associated with a significant survival benefit for colorectal and gastric cancer, but not for pancreatic cancer. (Source: Cancers)
Source: Cancers - April 17, 2019 Category: Cancer & Oncology Authors: Petrelli Zaniboni Ghidini Ghidini Turati Pizzo Ratti Libertini Tomasello Tags: Review Source Type: research

Cancers, Vol. 11, Pages 551: Genetic Variants as Predictive Markers for Ototoxicity and Nephrotoxicity in Patients with Locally Advanced Head and Neck Cancer Treated with Cisplatin-Containing Chemoradiotherapy (The PRONE Study)
In conclusion, we showed prospectively that in LAHNC patients genetic variants in ACYP2 are significantly associated with clinically determined ototoxicity. Validation studies are necessary to prove the added value for individualized treatments plans in these patients. (Source: Cancers)
Source: Cancers - April 17, 2019 Category: Cancer & Oncology Authors: Chantal M. Driessen Janneke C. Ham Maroeska te Loo Esther van Meerten Maurits van Lamoen Marina H. Hakobjan Robert P. Takes Winette T. van der Graaf Johannes H. Kaanders Marieke J.H. Coenen Carla M. van Herpen Tags: Article Source Type: research

Cancers, Vol. 11, Pages 552: Clinical Implications of Noncoding Indels in the Surfactant-Encoding Genes in Lung Cancer
In this study, we recruited 94 patients with 113 lung cancers (88 adenocarcinomas, 16 squamous cell carcinomas, and nine other histologies) who had undergone surgery in our department. A cancer panel was designed in-house for analyzing the noncoding regions, and targeted sequencing was performed. Indels in the noncoding region of surfactant-encoding genes were identified in 29/113 (25.7%) cases and represent the precise cell of origin for the lung cancer, irrespective of histological type and/or disease stage. In clinical practice, these indels may be used as clonal markers in patients with multiple cancers and to determin...
Source: Cancers - April 17, 2019 Category: Cancer & Oncology Authors: Nakagomi Hirotsu Goto Shikata Yokoyama Higuchi Otake Amemiya Oyama Mochizuki Omata Tags: Article Source Type: research

Cancers, Vol. 11, Pages 547: Novel Insights of Lymphomagenesis of Helicobacter pylori-Dependent Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
Ann-Lii Cheng Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most common subtype of gastric lymphoma. Most gastric MALT lymphomas are characterized by their association with the Helicobacter pylori (HP) infection and are cured by first-line HP eradication therapy (HPE). Several studies have been conducted to investigate why most gastric MALT lymphomas remain localized, are dependent on HP infection, and show HP-specific intratumoral T-cells (e.g., CD40-mediated signaling, T-helper-2 (Th2)-type cytokines, chemokines, costimulatory molecules, and FOXP3+ regulatory T-cells) and their communication with B...
Source: Cancers - April 17, 2019 Category: Cancer & Oncology Authors: Sung-Hsin Kuo Ming-Shiang Wu Kun-Huei Yeh Chung-Wu Lin Ping-Ning Hsu Li-Tzong Chen Ann-Lii Cheng Tags: Review Source Type: research

Cancers, Vol. 11, Pages 548: Dasatinib Treatment Increases Sensitivity to c-Met Inhibition in Triple-Negative Breast Cancer Cells
hn Crown Norma O’Donovan In pre-clinical studies, triple-negative breast cancer (TNBC) cells have demonstrated sensitivity to the multi-targeted kinase inhibitor dasatinib; however, clinical trials with single-agent dasatinib showed limited efficacy in unselected populations of breast cancer, including TNBC. To study potential mechanisms of resistance to dasatinib in TNBC, we established a cell line model of acquired dasatinib resistance (231-DasB). Following an approximately three-month exposure to incrementally increasing concentrations of dasatinib (200 nM to 500 nM) dasatinib, 231-DasB cells were resistant ...
Source: Cancers - April 17, 2019 Category: Cancer & Oncology Authors: Patricia Gaule Nupur Mukherjee Brendan Corkery Alex J. Eustace Kathy Gately Sandra Roche Robert O ’Connor Kenneth J. O ’Byrne Naomi Walsh Michael J. Duffy John Crown Norma O ’Donovan Tags: Article Source Type: research

Cancers, Vol. 11, Pages 549: Swallowing Safety and Efficiency after Open Partial Horizontal Laryngectomy: A Videofluoroscopic Study
In conclusion, swallowing safety was affected by incomplete laryngeal closure, while swallowing efficiency was affected by increased pharyngeal transit time, reduced upper esophageal sphincter opening, and incomplete tongue base retraction. The identified physio-pathological mechanisms could represent targets for rehabilitative and surgical approaches in patients with dysphagia after OPHL. (Source: Cancers)
Source: Cancers - April 17, 2019 Category: Cancer & Oncology Authors: Nicole Pizzorni Antonio Schindler Micol Castellari Marco Fantini Erika Crosetti Giovanni Succo Tags: Article Source Type: research

Cancers, Vol. 11, Pages 546: Frequent Occurrence of NRAS and BRAF Mutations in Human Acral Naevi
Hadaschik Klaus G. Griew. Acral naevi are benign melanocytic tumors occurring at acral sites. Occasionally they can progress to become malignant tumors (melanomas). The genetics of acral naevi have not been assessed in larger studies. In our study, a large cohort of 130 acral naevi was screened for gene mutations known to be important in other naevi and melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with clinicopathological parameters. Frequent mutations in genes activating the MAP kinase pathway were identified, including n = 87 (67%) BRAF, n = 24 (18%) NRAS, and one (1%) M...
Source: Cancers - April 16, 2019 Category: Cancer & Oncology Authors: Philipp Jansen Ioana Cosgarea Rajmohan Murali Inga M öller Antje Sucker Cindy Franklin Annette Paschen Anne Zaremba Titus J. Brinker Ingo Stoffels Dirk Schadendorf Joachim Klode Eva Hadaschik Klaus G. Griewank Tags: Article Source Type: research

Cancers, Vol. 11, Pages 534: Gastric Cancer in Northern Canadian Populations: A Focus on Cardia and Non-Cardia Subsites
This study has, for the first time, quantified the incidence of CGC and NCGC for the NT and YT, providing new insights into the burden of these cancers among northern Canadian populations. (Source: Cancers)
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Amy Colquhoun Heather Hannah Andr é Corriveau Brendan Hanley Yan Yuan Karen J. Goodman The CANHelp Working Group The CANHelp Working Group Tags: Article Source Type: research

Cancers, Vol. 11, Pages 535: The Association between Salt and Potential Mediators of the Gastric Precancerous Process
Conclusion: In humans, salt was associated with an increase in epithelial damage in stomachs with more severe previous H. pylori-induced chronic inflammation. (Source: Cancers)
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Susan Thapa Lori A. Fischbach Robert Delongchamp Mohammed F. Faramawi Mohammed Orloff Tags: Brief Report Source Type: research

Cancers, Vol. 11, Pages 536: Rising Serum Uric Acid Level Is Negatively Associated with Survival in Renal Cell Carcinoma
Conclusions: Increasing SUA was associated with poorer outcomes. Decreased SUA levels were associated with statin intake and lower stage disease as well as lack of progression to CKD and anemia. Further investigation is requisite. (Source: Cancers)
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Kendrick Yim Ahmet Bindayi Rana McKay Reza Mehrazin Omer A. Raheem Charles Field Aaron Bloch Robert Wake Stephen Ryan Anthony Patterson Ithaar H. Derweesh Tags: Article Source Type: research

Cancers, Vol. 11, Pages 537: A Characterization of Dendritic Cells and Their Role in Immunotherapy in Glioblastoma: From Preclinical Studies to Clinical Trials
chael Lim Glioblastoma (GBM) is the most common and fatal primary central nervous system malignancy in adults with a median survival of less than 15 months. Surgery, radiation, and chemotherapy are the standard of care and provide modest benefits in survival, but tumor recurrence is inevitable. The poor prognosis of GBM has made the development of novel therapies targeting GBM of paramount importance. Immunotherapy via dendritic cells (DCs) has garnered attention and research as a potential strategy to boost anti-tumor immunity in recent years. As the “professional” antigen processing and pr...
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Siddhartha Srivastava Christina Jackson Timothy Kim John Choi Michael Lim Tags: Review Source Type: research

Cancers, Vol. 11, Pages 538: Next-Generation Hedgehog/GLI Pathway Inhibitors for Cancer Therapy
erger The Hedgehog/Glioma-associated oncogene homolog (HH/GLI) signaling pathway regulates self-renewal of rare and highly malignant cancer stem cells (CSC), which have been shown to account for the initiation and maintenance of tumor growth as well as for drug resistance, metastatic spread and relapse. Efficacious therapeutic approaches targeting CSC pathways, such as HH/GLI signaling in combination with chemo, radiation or immunotherapy are, therefore, of high medical need. Pharmacological inhibition of HH/GLI pathway activity represents a promising approach to eliminate malignant CSC. Clinically approved HH/GLI path...
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Elisabeth Peer Suzana Tesanovic Fritz Aberger Tags: Review Source Type: research

Cancers, Vol. 11, Pages 539: Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review
la Silvestris Despite that the impact of immune checkpoint inhibitors on malignancies treatment is unprecedented, a lack of response to these molecules is observed in several cases. Differently from melanoma and non-small cell lung cancer, where the use of immune checkpoint inhibitors results in a high efficacy, the response rate in other tumors, such as gastrointestinal cancers, breast cancer, sarcomas, and part of genitourinary cancers remains low. The first strategy evaluated to improve the response rate to immune checkpoint inhibitors is the use of predictive factors for the response such as PD-L1 expression, tumor...
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Vito Longo Oronzo Brunetti Amalia Azzariti Domenico Galetta Patrizia Nardulli Francesco Leonetti Nicola Silvestris Tags: Review Source Type: research

Cancers, Vol. 11, Pages 540: The Prognostic Roles of Pretreatment Circulating Tumor Cells, Circulating Cancer Stem-Like Cells, and Programmed Cell Death-1 Expression on Peripheral Lymphocytes in Patients with Initially Unresectable, Recurrent or Metastatic Head and Neck Cancer: An Exploratory Study of Three Biomarkers in One-time Blood Drawing
Jason Chia-Hsun Hsieh Circulating tumor cells (CTCs) and immune status are strongly related to cancer prognosis, although few studies have examined both factors. This prospective observational study (ClinicalTrials.gov: NCT02420600) evaluated whether CTCs, circulating cancer stem-like cells (cCSCs), and peripheral lymphocytes with/without Programmed cell death protein 1 (PD-1) expression were associated with prognosis among patients receiving palliative chemotherapy for initially unresectable, recurrent/metastatic head and neck squamous cell carcinoma (rmHNSCC). Thirty-four patients were enrolled between January 2015...
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Pei-Hung Chang Min-Hsien Wu Sen-Yu Liu Hung-Ming Wang Wen-Kuan Huang Chun-Ta Liao Tzu-Chen Yen Shu-Hang Ng Jen-Shi Chen Yung-Chang Lin Hung-Chih Lin Jason Chia-Hsun Hsieh Tags: Article Source Type: research

Cancers, Vol. 11, Pages 542: Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Induces Intracellular Ca2+ Release through the Two-Pore Channel TPC1 in Metastatic Colorectal Cancer Cells
ntagna Francesco Moccia Nicotinic acid adenine dinucleotide phosphate (NAADP) gates two-pore channels 1 and 2 (TPC1 and TPC2) to elicit endo-lysosomal (EL) Ca2+ release. NAADP-induced EL Ca2+ signals may be amplified by the endoplasmic reticulum (ER) through the Ca2+-induced Ca2+ release mechanism (CICR). Herein, we aimed at assessing for the first time the role of EL Ca2+ signaling in primary cultures of human metastatic colorectal carcinoma (mCRC) by exploiting Ca2+ imaging and molecular biology techniques. The lysosomotropic agent, Gly-Phe β-naphthylamide (GPN), and nigericin, which dissipates the &am...
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Pawan Faris Giorgia Pellavio Federica Ferulli Francesca Di Nezza Mudhir Shekha Dmitry Lim Marcello Maestri Germano Guerra Luigi Ambrosone Paolo Pedrazzoli Umberto Laforenza Daniela Montagna Francesco Moccia Tags: Article Source Type: research

Cancers, Vol. 11, Pages 541: Low CD8+ T Cell Infiltration and High PD-L1 Expression Are Associated with Level of CD44+/CD133+ Cancer Stem Cells and Predict an Unfavorable Prognosis in Pancreatic Cancer
n-Shen Shan Cancer immunotherapy targeting immune checkpoints has exhibited promising clinical outcomes in many cancers, but it offers only limited benefits for pancreatic cancer (PC). Cancer stem cells (CSCs), a minor subpopulation of cancer cells, play important roles in tumor initiation, progression, and drug resistance. Accumulating evidence suggests that CSCs employ immunosuppressive effects to evade immune system recognition. However, the clinical implications of the associations among CD8+ T cells infiltration, programmed death receptor ligand-1 (PD-L1) expression, and CSCs existence are poorly understood in PC....
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Ya-Chin Hou Ying-Jui Chao Min-Hua Hsieh Hui-Ling Tung Hao-Chen Wang Yan-Shen Shan Tags: Article Source Type: research

Cancers, Vol. 11, Pages 543: 18F-FDG-PET Can Predict Microvessel Density in Head and Neck Squamous Cell Carcinoma
Conclusion: 8F-FDG-PET parameters correlate statistically significantly with MVD in HNSCC. SUVmax may be used for discrimination of tumors with high tumor-related MVD. (Source: Cancers)
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Alexey Surov Hans Jonas Meyer Anne-Kathrin H öhn Andreas Wienke Osama Sabri Sandra Purz Tags: Article Source Type: research

Cancers, Vol. 11, Pages 544: CHI3L1, NTRK2, 1p/19q and IDH Status Predicts Prognosis in Glioma
au Karine Durand Fabrice Lalloué The aim of this study was to identify relevant biomarkers for the prognosis of glioma considering current molecular changes such as IDH mutation and 1p19q deletion. Gene expression profiling was performed using the TaqMan Low Density Array and hierarchical clustering using 96 selected genes in 64 patients with newly diagnosed glioma. The expression dataset was validated on a large independent cohort from The Cancer Genome Atlas (TCGA) database. A differential expression panel of 26 genes discriminated two prognostic groups regardless of grade and molecular groups of tumors: P...
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Elise Deluche Barbara Bessette Stephanie Durand Fran çois Caire Val érie Rigau Sandrine Robert Alain Chaunavel Lionel Forestier Fran çois Labrousse Marie-Odile Jauberteau Karine Durand Fabrice Lallou é Tags: Article Source Type: research

Cancers, Vol. 11, Pages 545: Identification of KIF11 As a Novel Target in Meningioma
imon Unterberg Abdollahi Herold-Mende Kinesins play an important role in many physiological functions including intracellular vesicle transport and mitosis. The emerging role of kinesins in different cancers led us to investigate the expression and functional role of kinesins in meningioma. Therefore, we re-analyzed our previous microarray dataset of benign, atypical, and anaplastic meningiomas (n = 62) and got evidence for differential expression of five kinesins (KIFC1, KIF4A, KIF11, KIF14 and KIF20A). Further validation in an extended study sample (n = 208) revealed a significant upregulation of these genes...
Source: Cancers - April 15, 2019 Category: Cancer & Oncology Authors: Jungwirth Yu Moustafa Rapp Warta Jungk Sahm Dettling Zweckberger Lamszus Senft Loehr Ke ßler Ketter Westphal Debus von Deimling Simon Unterberg Abdollahi Herold-Mende Tags: Article Source Type: research

Cancers, Vol. 11, Pages 532: The Evolving Landscape of Cancer Stem Cells and Ways to Overcome Cancer Heterogeneity
atori Cancer stem cells (CSCs) with therapeutic resistance and plasticity can be found in various types of tumors and are recognized as attractive targets for treatments. As CSCs are derived from tissue stem or progenitor cells, and/or dedifferentiated mature cells, their signal transduction pathways are critical in the regulation of CSCs; chronic inflammation causes the accumulation of genetic mutations and aberrant epigenetic changes in these cells, potentially leading to the production of CSCs. However, the nature of CSCs appears to be stronger than the treatments of the past. To improve the treatments targeting CSC...
Source: Cancers - April 14, 2019 Category: Cancer & Oncology Authors: Hiroaki Taniguchi Yasunori Suzuki Yukikazu Natori Tags: Review Source Type: research

Cancers, Vol. 11, Pages 533: The Interplay of Autophagy and Tumor Microenvironment in Colorectal Cancer —Ways of Enhancing Immunotherapy Action
Cancers, Vol. 11, Pages 533: The Interplay of Autophagy and Tumor Microenvironment in Colorectal Cancer—Ways of Enhancing Immunotherapy Action Cancers doi: 10.3390/cancers11040533 Authors: Evangelos Koustas Panagiotis Sarantis Georgia Kyriakopoulou Athanasios G. Papavassiliou Michalis V. Karamouzis Autophagy as a primary homeostatic and catabolic process is responsible for the degradation and recycling of proteins and cellular components. The mechanism of autophagy has a crucial role in several cellular functions and its dysregulation is associated with tumorigenesis, tumor–stroma intera...
Source: Cancers - April 14, 2019 Category: Cancer & Oncology Authors: Evangelos Koustas Panagiotis Sarantis Georgia Kyriakopoulou Athanasios G. Papavassiliou Michalis V. Karamouzis Tags: Review Source Type: research

Cancers, Vol. 11, Pages 531: Efficacy of a Selective Binder of αVβ3 Integrin Linked to the Tyrosine Kinase Inhibitor Sunitinib in Ovarian Carcinoma Preclinical Models
Cancers, Vol. 11, Pages 531: Efficacy of a Selective Binder of αVβ3 Integrin Linked to the Tyrosine Kinase Inhibitor Sunitinib in Ovarian Carcinoma Preclinical Models Cancers doi: 10.3390/cancers11040531 Authors: Andrea Sartori Cristina Corno Michelandrea De Cesare Eugenio Scanziani Lucia Minoli Lucia Battistini Franca Zanardi Paola Perego Ovarian carcinoma, the most lethal gynecological cancer, is characterized by late diagnosis, with drug resistance limiting the efficacy of platinum-based therapy. Since some integrins are upregulated in cancer, including ovarian carcinoma, they represent ...
Source: Cancers - April 13, 2019 Category: Cancer & Oncology Authors: Andrea Sartori Cristina Corno Michelandrea De Cesare Eugenio Scanziani Lucia Minoli Lucia Battistini Franca Zanardi Paola Perego Tags: Article Source Type: research

Cancers, Vol. 11, Pages 522: Germline Missense Variants in BRCA1: New Trends and Challenges for Clinical Annotation
teiro Genetic testing allows for the identification of germline DNA variations, which are associated with a significant increase in the risk of developing breast cancer (BC) and ovarian cancer (OC). Detection of a BRCA1 or BRCA2 pathogenic variant triggers several clinical management actions, which may include increased surveillance and prophylactic surgery for healthy carriers or treatment with the PARP inhibitor therapy for carriers diagnosed with cancer. Thus, standardized validated criteria for the annotation of BRCA1 and BRCA2 variants according to their pathogenicity are necessary to support clinical decision-mak...
Source: Cancers - April 12, 2019 Category: Cancer & Oncology Authors: Volha A. Golubeva Thales C. Nepomuceno Alvaro N. A. Monteiro Tags: Review Source Type: research

Cancers, Vol. 11, Pages 524: Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death
oa Jesús Balsinde Hydroxy fatty acids are known to cause cell cycle arrest and apoptosis. The best studied of them, 9-hydroxystearic acid (9-HSA), induces apoptosis in cell lines by acting through mechanisms involving different targets. Using mass spectrometry-based lipidomic approaches, we show in this study that 9-HSA levels in human colorectal tumors are diminished when compared with normal adjacent tissue. Since this decrease could be compatible with an escape mechanism of tumors from 9-HSA-induced apoptosis, we investigated different features of the utilization of this hydroxyfatty acid in colon. We show ...
Source: Cancers - April 12, 2019 Category: Cancer & Oncology Authors: Juan P. Rodr íguez Carlos Guijas Alma M. Astudillo Julio M. Rubio Mar ía A. Balboa Jes ús Balsinde Tags: Article Source Type: research

Cancers, Vol. 11, Pages 523: Cyclin-Dependent Kinase 5 (CDK5)-Mediated Phosphorylation of Upstream Stimulatory Factor 2 (USF2) Contributes to Carcinogenesis
sa Y. Dimova The transcription factor USF2 is supposed to have an important role in tumor development. However, the regulatory mechanisms contributing to the function of USF2 are largely unknown. Cyclin-dependent kinase 5 (CDK5) seems to be of importance since high levels of CDK5 were found in different cancers associated with high USF2 expression. Here, we identified USF2 as a phosphorylation target of CDK5. USF2 is phosphorylated by CDK5 at two serine residues, serine 155 and serine 222. Further, phosphorylation of USF2 at these residues was shown to stabilize the protein and to regulate cellular growth and migration...
Source: Cancers - April 12, 2019 Category: Cancer & Oncology Authors: Tabughang Franklin Chi Tina Horbach Claudia G ötz Thomas Kietzmann Elitsa Y. Dimova Tags: Article Source Type: research

Cancers, Vol. 11, Pages 525: Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient ’s Survival
Cancers, Vol. 11, Pages 525: Transient Receptor Potential Mucolipin-1 Channels in Glioblastoma: Role in Patient’s Survival Cancers doi: 10.3390/cancers11040525 Authors: Maria Beatrice Morelli Consuelo Amantini Daniele Tomassoni Massimo Nabissi Antonella Arcella Giorgio Santoni A link between mucolipin channels and tumors has been recently suggested. Herein, we aim to investigate the transient receptor potential mucolipin (TRPML)-1 relevance in glioblastoma. The expression of this channel was evaluated via qRT-PCR and immunohistochemistry in biopsies from 66 glioblastoma patients and two human gliobl...
Source: Cancers - April 12, 2019 Category: Cancer & Oncology Authors: Maria Beatrice Morelli Consuelo Amantini Daniele Tomassoni Massimo Nabissi Antonella Arcella Giorgio Santoni Tags: Article Source Type: research

Cancers, Vol. 11, Pages 526: Automated Quantification of Extranuclear ER α using Phosphor-integrated Dots for Predicting Endocrine Therapy Resistance in HR+/HER2− Breast Cancer
Cancers, Vol. 11, Pages 526: Automated Quantification of Extranuclear ERα using Phosphor-integrated Dots for Predicting Endocrine Therapy Resistance in HR+/HER2− Breast Cancer Cancers doi: 10.3390/cancers11040526 Authors: Guo Tada Kitamura Hamada Miyashita Harada-Shoji Sato Hamanaka Tsuboi Harada Takano-Kasuya Okada Nakano Ohuchi Hayashi Ishida Gonda In addition to genomic signaling, Estrogen receptor alpha (ERα) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistanc...
Source: Cancers - April 12, 2019 Category: Cancer & Oncology Authors: Guo Tada Kitamura Hamada Miyashita Harada-Shoji Sato Hamanaka Tsuboi Harada Takano-Kasuya Okada Nakano Ohuchi Hayashi Ishida Gonda Tags: Article Source Type: research

Cancers, Vol. 11, Pages 527: Proteasome 26S Subunit, non-ATPase 3 (PSMD3) Regulates Breast Cancer by Stabilizing HER2 from Degradation
In this study, we investigated the expression level of Proteasome 26S subunit, non-ATPase 3 (PSMD3) in BC using BC cell lines, human BC tissue samples, Oncomine, and TCGA databases and studied the PSMD3-HER2 protein interaction. PSMD3 was upregulated in BC, particularly in the HER2+ subtype. PSMD3 immunostaining was detected in the cytoplasm and nucleus of BC tumor tissues. Strong interaction between PSMD3 and HER2 at the protein level was observed. Knockdown of PSMD3 significantly impaired the stability of HER2, inhibited BC cell proliferation and colony formation, and induced cell apoptosis. Ubiquitination process was st...
Source: Cancers - April 12, 2019 Category: Cancer & Oncology Authors: Fararjeh Chen Ho Cheng Liu Chang Chang Wu Tu Tags: Article Source Type: research

Cancers, Vol. 11, Pages 528: The Role of HOX Transcription Factors in Cancer Predisposition and Progression
g Wei Homeobox (HOX) transcription factors, encoded by a subset of homeodomain superfamily genes, play pivotal roles in many aspects of cellular physiology, embryonic development, and tissue homeostasis. Findings over the past decade have revealed that mutations in HOX genes can lead to increased cancer predisposition, and HOX genes might mediate the effect of many other cancer susceptibility factors by recognizing or executing altered genetic information. Remarkably, several lines of evidence highlight the interplays between HOX transcription factors and cancer risk loci discovered by genome-wide association studies, ...
Source: Cancers - April 12, 2019 Category: Cancer & Oncology Authors: Bo Li Qilai Huang Gong-Hong Wei Tags: Review Source Type: research

Cancers, Vol. 11, Pages 529: Role of Macrophage Migration Inhibitory Factor (MIF) in Melanoma
Fabrice Journe Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine involved in the carcinogenesis of many cancer types. Here, we review the published experimental and clinical data for MIF and its involvement in melanoma. All reported data show that MIF is overexpressed in melanoma cells, especially in case of metastatic disease. Clinical studies also indicate that high MIF expression is positively associated with aggressiveness of the disease. Some data also highlight the implication of MIF in angiogenesis, immunity and metastasis in melanoma cell lines, as well as the availability of different th...
Source: Cancers - April 12, 2019 Category: Cancer & Oncology Authors: Laura Soumoy Nad ège Kindt Ghanem Ghanem Sven Saussez Fabrice Journe Tags: Review Source Type: research

Cancers, Vol. 11, Pages 530: Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis
Conclusion: The identified prognostic and predictive factors can be included and analyzed in future RCTs and be of guidance for nomograms. Further validation should be performed in large patient cohorts. (Source: Cancers)
Source: Cancers - April 12, 2019 Category: Cancer & Oncology Authors: van den Ende ter Veer Mali van Berge Henegouwen Hulshof van Oijen van Laarhoven Tags: Article Source Type: research

Cancers, Vol. 11, Pages 518: Identification of Cancer Stem Cell Molecular Markers and Effects of hsa-miR-21-3p on Stemness in Esophageal Squamous Cell Carcinoma
u Ran Liu Cancer stem cells (CSCs) are closely related to tumor resistance and tumor recurrence in esophageal squamous cell carcinoma (ESCC). The lack of specific biomarkers to identify and isolate CSCs has led to the slow progression of research on CSCs in ESCC. Here, we established a method to identify and isolate CSCs in ESCC using fluorescence-activated cell sorting with combined surface biomarkers including CD71, CD271, and CD338. CD71−/CD271+/CD338+ subpopulation cells possessed more stem cell properties in proliferation, self-renewal, differentiation, metastasis, drug resistance, and tumorigenesi...
Source: Cancers - April 11, 2019 Category: Cancer & Oncology Authors: Zhikui Gao Hui Liu Yajuan Shi Lihong Yin Yong Zhu Ran Liu Tags: Article Source Type: research

Cancers, Vol. 11, Pages 520: Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer
Lee Kim Increased detection of plasma lysophosphatidic acid (LPA) has been proposed as a potential diagnostic biomarker in ovarian cancer, but inconsistency exists in these reports. It has been shown that LPA can undergo an artificial increase during sample processing and analysis, which has not been accounted for in ovarian cancer research. The aim of this study is to provide a potential explanation about how the artificial increase in LPA may have interfered with previous LPA analysis in ovarian cancer research. Using an established LC-MS method, we measured LPA and other lysophospholipid levels in plasma obta...
Source: Cancers - April 11, 2019 Category: Cancer & Oncology Authors: Yagi Shoaib Kuschner Nishikimi Becker Lee Kim Tags: Article Source Type: research

Cancers, Vol. 11, Pages 521: Dendritic Cells and Cancer: From Biology to Therapeutic Intervention
Waithman Inducing effective anti-tumor immunity has become a major therapeutic strategy against cancer. Dendritic cells (DC) are a heterogenous population of antigen presenting cells that infiltrate tumors. While DC play a critical role in the priming and maintenance of local immunity, their functions are often diminished, or suppressed, by factors encountered in the tumor microenvironment. Furthermore, DC populations with immunosuppressive activities are also recruited to tumors, limiting T cell infiltration and promoting tumor growth. Anti-cancer therapies can impact the function of tumor-associated DC and/or alter t...
Source: Cancers - April 11, 2019 Category: Cancer & Oncology Authors: Wylie Macri Mintern Waithman Tags: Review Source Type: research

Cancers, Vol. 11, Pages 517: Cancer Vaccines Co-Targeting HER2/Neu and IGF1R
Conclusions: Multi-engineered adjuvanted cancer cell vaccines can break the tolerance towards a highly tolerized RTK, such as IGF1R. Cell vaccines co-targeting HER2/neu and IGF1R elicited low levels of specific antibodies that slightly delayed onset of HER2/neu-driven, IGF1R-dependent tumors. (Source: Cancers)
Source: Cancers - April 11, 2019 Category: Cancer & Oncology Authors: Carla De Giovanni Lorena Landuzzi Arianna Palladini Marianna Lucia Ianzano Giordano Nicoletti Francesca Ruzzi Augusto Amici Stefania Croci Patrizia Nanni Pier-Luigi Lollini Tags: Article Source Type: research

Cancers, Vol. 11, Pages 519: Establishment and Characterization of a New Intrahepatic Cholangiocarcinoma Cell Line Resistant to Gemcitabine
In conclusion, we characterized a new GEM resistance ICC model that could be exploited either to study alternative mechanisms of resistance or to explore new therapies. (Source: Cancers)
Source: Cancers - April 11, 2019 Category: Cancer & Oncology Authors: Chiara Varamo Caterina Peraldo-Neia Paola Ostano Marco Basiric ò Chiara Raggi Paola Bernabei Tiziana Venesio Enrico Berrino Massimo Aglietta Francesco Leone Giuliana Cavalloni Tags: Article Source Type: research

Cancers, Vol. 11, Pages 504: Gastric Microbiota in Helicobacter pylori-Negative and -Positive Gastritis Among High Incidence of Gastric Cancer Area
Yoshio Yamaoka Helicobacter pylori (H. pylori) related chronic gastritis is a well-known major etiological factor for gastric cancer development. However, H. pylori-negative gastritis (HpN) is not well described. We aimed to examine gastric mucosal microbiota in HpN compared to H. pylori-positive gastritis (HpP) and H. pylori-negative non-gastritis group (control). Here, we studied 11 subjects with HpN, 40 with HpP and 24 controls. We performed endoscopy with six gastric biopsies. Comparison groups were defined based on strict histological criteria for the disease and H. pylori diagnosis. We used 16S rRNA gene amplico...
Source: Cancers - April 10, 2019 Category: Cancer & Oncology Authors: Boldbaatar Gantuya Hashem B. El-Serag Takashi Matsumoto Nadim J. Ajami Khasag Oyuntsetseg Dashdorj Azzaya Tomohisa Uchida Yoshio Yamaoka Tags: Article Source Type: research

Cancers, Vol. 11, Pages 505: Ethanol-Mediated Stress Promotes Autophagic Survival and Aggressiveness of Colon Cancer Cells via Activation of Nrf2/HO-1 Pathway
varuso Marianna Lauricella Epidemiological studies suggest that chronic alcohol consumption is a lifestyle risk factor strongly associated with colorectal cancer development and progression. The aim of the present study was to examine the effect of ethanol (EtOH) on survival and progression of three different colon cancer cell lines (HCT116, HT29, and Caco-2). Our data showed that EtOH induces oxidative and endoplasmic reticulum (ER) stress, as demonstrated by reactive oxygen species (ROS) and ER stress markers Grp78, ATF6, PERK and, CHOP increase. Moreover, EtOH triggers an autophagic response which is accompanied b...
Source: Cancers - April 10, 2019 Category: Cancer & Oncology Authors: Cesare Cernigliaro Antonella D ’Anneo Daniela Carlisi Michela Giuliano Antonella Marino Gammazza Rosario Barone Lucia Longhitano Francesco Cappello Sonia Emanuele Alfio Distefano Claudia Campanella Giuseppe Calvaruso Marianna Lauricella Tags: Article Source Type: research

Cancers, Vol. 11, Pages 506: Treatment of a Malignant Soft Tissue Tumor Arising in the Vicinity of the Sciatic Nerve with an In-Situ Preparation Technique and Intensive Multidisciplinary Therapy
Hideki Murakami Preservation of the sciatic nerve is difficult in cases of highly malignant soft tissuetumors closely surrounding the nerve. Herein, we present the first case of preservation of thisnerve by combining an in-situ preparation technique (ISP; a technique enabling the preparation ofneurovascular bundles without contamination by tumor cells) with intensive concurrent neoadjuvantchemo-radiotherapy with hyperthermia (RHC; radio-hyperthermo-chemotherapy). A 62-year-oldman presented with a soft tissue mass in the right thigh and was diagnosed with undifferentiatedpleomorphic sarcoma. The tumor arose in the mul...
Source: Cancers - April 10, 2019 Category: Cancer & Oncology Authors: Hisaki Aiba Katsuhiro Hayashi Satoshi Yamada Hideki Okamoto Hiroaki Kimura Shinji Miwa Hiroyuki Inatani Takanobu Otsuka Hideki Murakami Tags: Case Report Source Type: research

Cancers, Vol. 11, Pages 507: Integrative Analysis Reveals Subtype-Specific Regulatory Determinants in Triple Negative Breast Cancer
akowski Different breast cancer (BC) subtypes have unique gene expression patterns, but their regulatory mechanisms have yet to be fully elucidated. We hypothesized that the top upregulated (Yin) and downregulated (Yang) genes determine the fate of cancer cells. To reveal the regulatory determinants of these Yin and Yang genes in different BC subtypes, we developed a lasso regression model integrating DNA methylation (DM), copy number variation (CNV) and microRNA (miRNA) expression of 391 BC patients, coupled with miRNA–target interactions and transcription factor (TF) binding sites. A total of 25, 20, 15...
Source: Cancers - April 10, 2019 Category: Cancer & Oncology Authors: Shujun Huang Wayne Xu Pingzhao Hu Ted M. Lakowski Tags: Article Source Type: research

Cancers, Vol. 11, Pages 508: Kinase Regulation of HOX Transcription Factors
Morgan The HOX genes are a group of homeodomain-containing transcription factors that play important regulatory roles in early development, including the establishment of cell and tissue identity. HOX expression is generally reduced in adult cells but is frequently re-established as an early event in tumour formation and supports an oncogenic phenotype. HOX transcription factors are also involved in cell cycle regulation and DNA repair, along with normal adult physiological process including stem cell renewal. There have been extensive studies on the mechanism by which HOX proteins regulate transcription, with particu...
Source: Cancers - April 10, 2019 Category: Cancer & Oncology Authors: Monika Primon Keith D. Hunter Hardev S. Pandha Richard Morgan Tags: Review Source Type: research

Cancers, Vol. 11, Pages 509: Development of a New Nomogram Including Neutrophil-to-Lymphocyte Ratio to Predict Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization
yu Sung Rim Jun Yong Park The neutrophil-to-lymphocyte ratio (NLR) has recently been reported to predict the prognosis of hepatocellular carcinoma (HCC). We explored whether NLR predicted the survival of patients with HCC undergoing transarterial chemoembolization (TACE), and developed a predictive model. In total, 1697 patients with HCC undergoing TACE as first-line therapy at two university hospitals were enrolled (derivation set n = 921, internal validation set n = 395, external validation set n = 381). The tumor size, tumor number, AFP level, vascular invasion, Child–Pugh score, objective response a...
Source: Cancers - April 10, 2019 Category: Cancer & Oncology Authors: Young Eun Chon Hana Park Hye Kyung Hyun Yeonjung Ha Mi Na Kim Beom Kyung Kim Joo Ho Lee Seung Up Kim Do Young Kim Sang Hoon Ahn Seong Gyu Hwang Kwang-Hyub Han Kyu Sung Rim Jun Yong Park Tags: Article Source Type: research

Cancers, Vol. 11, Pages 510: Cancer Pain Assessment and Classification
dra More than half of patients affected by cancer experience pain of moderate-to-severe intensity, often in multiple sites, and of different etiologies and underlying mechanisms. The heterogeneity of pain mechanisms is expressed with the fluctuating nature of cancer pain intensity and clinical characteristics. Traditional ways of classifying pain in the cancer population include distinguishing pain etiology, clinical characteristics related to pain and the patient, pathophysiology, and the use of already validated classification systems. Concepts like breakthrough, nociceptive, neuropathic, and mixed pain are very impo...
Source: Cancers - April 10, 2019 Category: Cancer & Oncology Authors: Augusto Caraceni Morena Shkodra Tags: Review Source Type: research