Cancers, Vol. 10, Pages 348: Role of COX-2/PGE2 Mediated Inflammation in Oral Squamous Cell Carcinoma
artin A significant amount of research indicates that the cyclooxygenase/prostaglandin E2 (PGE2) pathway of inflammation contributes to the development and progression of a variety of cancers, including squamous cell carcinoma, or the oral cavity and oropharynx (OSCC). Although there have been promising results from studies examining the utility of anti-inflammatory drugs in the treatment of OSCC, this strategy has been met with only variable success and these drugs are also associated with toxicities that make them inappropriate for some OSCC patients. Improved inflammation-targeting therapies require continued study ...
Source: Cancers - September 22, 2018 Category: Cancer & Oncology Authors: Walaa Hamed Shaker Nasry Juan Carlos Rodriguez-Lecompte Chelsea K. Martin Tags: Review Source Type: research

Cancers, Vol. 10, Pages 345: Castration-Resistant Prostate Cancer Refractory to Second-Generation Androgen Receptor Axis-Targeted Agents: Opportunities and Challenges
shi Kobayashi Second-generation androgen receptor axis-targeted (ARAT) agents, namely abiraterone and enzalutamide, enable stronger blockade of the androgen receptor (AR) axis and longer survival of men with castration-resistant prostate cancer (CRPC). However, the extent of the improved survival remains insufficient and the majority of patients eventually develop resistance to these novel agents. Some patients develop resistance against ARAT treatment through mechanisms termed “complete AR independence” or “AR indifference”, and no longer require activation of th...
Source: Cancers - September 21, 2018 Category: Cancer & Oncology Authors: Yuki Kita Takayuki Goto Shusuke Akamatsu Toshinari Yamasaki Takahiro Inoue Osamu Ogawa Takashi Kobayashi Tags: Review Source Type: research

Cancers, Vol. 10, Pages 346: The “Yin and Yang” of Natural Compounds in Anticancer Therapy of Triple-Negative Breast Cancers
Cancers, Vol. 10, Pages 346: The “Yin and Yang” of Natural Compounds in Anticancer Therapy of Triple-Negative Breast Cancers Cancers doi: 10.3390/cancers10100346 Authors: Elizabeth Varghese Samson Mathews Samuel Mariam Abotaleb Sohaila Cheema Ravinder Mamtani Dietrich Büsselberg Among the different types of breast cancers, triple-negative breast cancers (TNBCs) are highly aggressive, do not respond to conventional hormonal/human epidermal growth factor receptor 2 (HER2)-targeted interventions due to the lack of the respective receptor targets, have chances of early recurrence, metastasize...
Source: Cancers - September 21, 2018 Category: Cancer & Oncology Authors: Elizabeth Varghese Samson Mathews Samuel Mariam Abotaleb Sohaila Cheema Ravinder Mamtani Dietrich B üsselberg Tags: Review Source Type: research

Cancers, Vol. 10, Pages 347: NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells
Fujimoto Chiho Ohbayashi The nucleus accumbens-associated protein 1 (NACC1) is a transcription factor constitutively expressed in the urothelium, where it regulates cell growth, senescence, autophagy, and epithelial-mesenchymal transition. microRNA (miRNA) constitutes a class of small non-coding RNAs which are involved in cell proliferation, differentiation, and progression of tumors. miRNAs and their target molecules are utilized for molecular diagnosis of urothelial carcinoma. NACC1 is one of several putative target molecules of miR-331-3p, and is associated with cell proliferation in cancers such as prostate and ...
Source: Cancers - September 21, 2018 Category: Cancer & Oncology Authors: Kohei Morita Tomomi Fujii Hiroe Itami Tomoko Uchiyama Tokiko Nakai Kinta Hatakeyama Aya Sugimoto Makito Miyake Yasushi Nakai Nobumichi Tanaka Keiji Shimada Masaharu Yamazaki Kiyohide Fujimoto Chiho Ohbayashi Tags: Article Source Type: research

Cancers, Vol. 10, Pages 344: The Unfolded Protein Response in Breast Cancer
Afshin Samali In 2018, in the US alone, it is estimated that 268,670 people will be diagnosed with breast cancer, and that 41,400 will die from it. Since breast cancers often become resistant to therapies, and certain breast cancers lack therapeutic targets, new approaches are urgently required. A cell-stress response pathway, the unfolded protein response (UPR), has emerged as a promising target for the development of novel breast cancer treatments. This pathway is activated in response to a disturbance in endoplasmic reticulum (ER) homeostasis but has diverse physiological and disease-specific functions. In breast...
Source: Cancers - September 21, 2018 Category: Cancer & Oncology Authors: Eoghan P. McGrath Susan E. Logue Katarzyna Mnich Shane Deegan Richard J äger Adrienne M. Gorman Afshin Samali Tags: Review Source Type: research

Cancers, Vol. 10, Pages 342: Mechanisms Underlying the Action and Synergism of Trastuzumab and Pertuzumab in Targeting HER2-Positive Breast Cancer
Wang Human epidermal growth factor receptor (HER) 2 (HER2) is overexpressed in 20–30% of breast cancers. HER2 is a preferred target for treating HER2-positive breast cancer. Trastuzumab and pertuzumab are two HER2-targeted monoclonal antibodies approved by the Food and Drug Administration (FDA) to use as adjuvant therapy in combination with docetaxel to treat metastatic HER2-positive breast cancer. Adding the monoclonal antibodies to treatment regimen has changed the paradigm for treatment of HER2-positive breast cancer. Despite improving outcomes, the percentage of the patients who benefit from the trea...
Source: Cancers - September 20, 2018 Category: Cancer & Oncology Authors: Babak Nami Hamid Maadi Zhixiang Wang Tags: Review Source Type: research

Cancers, Vol. 10, Pages 343: Characterization of Precursor-Dependent Steroidogenesis in Human Prostate Cancer Models
Tomlinson Guns Castration-resistant prostate tumors acquire the independent capacity to generate androgens by upregulating steroidogenic enzymes or using steroid precursors produced by the adrenal glands for continued growth and sustainability. The formation of steroids was measured by liquid chromatography-mass spectrometry in LNCaP and 22Rv1 prostate cancer cells, and in human prostate tissues, following incubation with steroid precursors (22-OH-cholesterol, pregnenolone, 17-OH-pregnenolone, progesterone, 17-OH-progesterone). Pregnenolone, progesterone, 17-OH-pregnenolone, and 17-OH-progesterone increased C21 steroi...
Source: Cancers - September 20, 2018 Category: Cancer & Oncology Authors: Subrata Deb Steven Pham Dong-Sheng Ming Mei Yieng Chin Hans Adomat Antonio Hurtado-Coll Martin E. Gleave Emma S. Tomlinson Guns Tags: Article Source Type: research

Cancers, Vol. 10, Pages 340: Autologous Transplantation for Older Adults with AML
s Pabst While the majority of patients with acute myeloid leukemia (AML) are above the age of 65 years at diagnosis, the outcome of older AML patients remains disappointing. Even if standard intensive chemotherapy induces morphologic complete remission (CR1), relapses in older AML patients are common leading to poor long-term survival outcomes. Since autologous hematopoietic stem cell transplantation (HCT) offers distinct anti-leukemic effectiveness while avoiding graft-versus-host disease associated with allogeneic transplantation, it represents an option for consolidation treatment in selected older AML patients. How...
Source: Cancers - September 19, 2018 Category: Cancer & Oncology Authors: Beatrice U. Mueller Katja Seipel Ulrike Bacher Thomas Pabst Tags: Review Source Type: research

Cancers, Vol. 10, Pages 341: Deficiency in STAT1 Signaling Predisposes Gut Inflammation and Prompts Colorectal Cancer Development
itlaltepetl Salinas Abhay Satoskar Luis Terrazas Signal transducer and activator of transcription 1 (STAT1) is part of the Janus kinase (JAK/STAT) signaling pathway that controls critical events in intestinal immune function related to innate and adaptive immunity. Recent studies have implicated STAT1 in tumor–stroma interactions, and its expression and activity are perturbed during colon cancer. However, the role of STAT1 during the initiation of inflammation-associated cancer is not clearly understood. To determine the role of STAT1 in colitis-associated colorectal cancer (CAC), we analyzed the tumor develo...
Source: Cancers - September 19, 2018 Category: Cancer & Oncology Authors: Sonia Leon-Cabrera Armando V ázquez-Sandoval Emmanuel Molina-Guzman Yael Delgado-Ramirez Norma Delgado-Buenrostro Blanca Callejas Yolanda Chirino Carlos P érez-Plasencia Miriam Rodr íguez-Sosa Jonadab Olgu ín Citlaltepetl Salinas Abhay Satoskar Luis T Tags: Article Source Type: research

Cancers, Vol. 10, Pages 338: Phase I Study of Carbon Ion Radiotherapy and Image-Guided Brachytherapy for Locally Advanced Cervical Cancer
up for Gynecologic Cancer A phase I study was performed to determine the recommended dose of carbon ion radiotherapy and 3D image-guided brachytherapy for histologically confirmed stage II (≥4 cm), III, or IVA cervical cancer. Dose-limiting toxicities (treatment-related toxicities occurring within three months from the start of carbon ion radiotherapy) included Grade 3 non-hematological toxicity, Grade 4 hematological toxicity, or interruption of treatment for more than two weeks due to treatment-related toxicities. Carbon ion radiotherapy consisted of whole-pelvic irradiation with 36.0 Gy (relative biological effec...
Source: Cancers - September 18, 2018 Category: Cancer & Oncology Authors: Tatsuya Ohno Shin-ei Noda Kazutoshi Murata Yuya Yoshimoto Noriyuki Okonogi Ken Ando Tomoaki Tamaki Shingo Kato Takashi Hirakawa Tatsuya Kanuma Takashi Minegishi Takashi Nakano on behalf of the Working Group for Gynecologic Cancer Tags: Article Source Type: research

Cancers, Vol. 10, Pages 339: Current Immunotherapeutic Approaches in T Cell Non-Hodgkin Lymphomas
llert T cell non-Hodgkin lymphoma (T-NHL) is a rare and heterogeneous group of neoplasms of the lymphoid system. With the exception of a few relatively indolent entities, T-NHL is typically aggressive, treatment resistant, and associated with poor prognosis. Relatively few options with proven clinical benefit are available for patients with relapsed or refractory disease. Immunotherapy has emerged as a promising treatment for the management of patients with hematological malignancies. The identification of tumor antigens has provided a large number of potential targets. Therefore, several monoclonal antibodies (alemtuz...
Source: Cancers - September 18, 2018 Category: Cancer & Oncology Authors: Teresa Poggio Justus Duyster Anna L. Illert Tags: Review Source Type: research

Cancers, Vol. 10, Pages 337: Oxidative Phosphorylation: A Target for Novel Therapeutic Strategies Against Ovarian Cancer
atankar Aerobic glycolysis is an important metabolic adaptation of cancer cells. There is growing evidence that oxidative phosphorylation is also an active metabolic pathway in many tumors, including in high grade serous ovarian cancer. Metastasized ovarian tumors use fatty acids for their energy needs. There is also evidence of ovarian cancer stem cells privileging oxidative phosphorylation (OXPHOS) for their metabolic needs. Metformin and thiazolidinediones such as rosiglitazone restrict tumor growth by inhibiting specific steps in the mitochondrial electron transport chain. These observations suggest that strategies...
Source: Cancers - September 18, 2018 Category: Cancer & Oncology Authors: Amruta P. Nayak Arvinder Kapur Lisa Barroilhet Manish S. Patankar Tags: Review Source Type: research

Cancers, Vol. 10, Pages 336: Revisiting Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Cancer: Saint or Sinner?
sin Human neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein present in a wide variety of tissues and cell types. NGAL exists as a 25 kDa monomer, a 46 kDa homodimer (the most abundant form in healthy subjects) and a 130 kDa disulfide-linked heterodimer bound to latent matrix metalloproteinase-9. Dysregulated expression of NGAL in human malignancies suggests its value as a clinical marker. A growing body of evidence is highlighting NGAL’s paradoxical (i.e., both beneficial and detrimental) effects on cellular processes associated with tumor development (proliferation, survival, migration,...
Source: Cancers - September 18, 2018 Category: Cancer & Oncology Authors: Brigitte Bauvois Santos A. Susin Tags: Review Source Type: research

Cancers, Vol. 10, Pages 335: Combination of EGFR Inhibitor Lapatinib and MET Inhibitor Foretinib Inhibits Migration of Triple Negative Breast Cancer Cell Lines
rota Nowak Triple-negative breast cancer (TNBC) is the most challenging subtype to treat due to the lack of estrogen receptor, progesterone receptor, and HER2 expression, which excludes the usage of directed targeted therapy against them. Promising therapeutic targets are the hepatocyte growth factor receptor (MET) and epidermal growth factor receptor (EGFR), which expression is frequently elevated in TNBC. Inhibitors of these receptors used as monotherapy are often ineffective. Due to that, we studied the efficacy of combined therapy targeting MET and EGFR simultaneously. Two TNBC cell lines were treated with lapatini...
Source: Cancers - September 17, 2018 Category: Cancer & Oncology Authors: Aleksandra Simiczyjew Ewelina Dratkiewicz Marleen Van Troys Christophe Ampe Ilona Stycze ń Dorota Nowak Tags: Article Source Type: research

Cancers, Vol. 10, Pages 334: Factors Secreted by Cancer-Associated Fibroblasts that Sustain Cancer Stem Properties in Head and Neck Squamous Carcinoma Cells as Potential Therapeutic Targets
This study investigates for the first time the crosstalk between stromal fibroblasts and cancer stem cell (CSC) biology in head and neck squamous cell carcinomas (HNSCC), with the ultimate goal of identifying effective therapeutic targets. The effects of conditioned media from cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) on the CSC phenotype were assessed by combining functional and expression analyses in HNSCC-derived cell lines. Further characterization of CAFs and NFs secretomes by mass spectrometry was followed by pharmacologic target inhibition. We demonstrate that factors secreted by CAFs but not...
Source: Cancers - September 17, 2018 Category: Cancer & Oncology Authors: Sa úl Álvarez-Teijeiro Cristina Garc ía-Inclán M. Ángeles Villaronga Pedro Casado Francisco Hermida-Prado Roc ío Granda-Díaz Juan P. Rodrigo Fernando Calvo Nagore del-R ío-Ibisate Alberto Gandarillas Francisco Mor ís Mario Hermsen Pedro Cutillas Tags: Article Source Type: research

Cancers, Vol. 10, Pages 333: Proton Beam Therapy in Combination with Intra-Arterial Infusion Chemotherapy for T4 Squamous Cell Carcinoma of the Maxillary Gingiva
This study aimed to evaluate the therapeutic effect and toxicity of proton beam therapy in combination with intra-arterial infusion chemotherapy in patients with squamous cell carcinoma of the maxillary gingiva. Between December 2010 and March 2016, 30 patients with T4 squamous cell carcinoma of the maxillary gingiva were treated with radiotherapy and retrograde intra-arterial infusion chemotherapy using cisplatin (20–40 mg/m2, 4–6 times). Radiotherapy was basically administered using boost proton beam therapy for primary tumor and neck lymph node tumors, following 36–40 Gy photon ...
Source: Cancers - September 15, 2018 Category: Cancer & Oncology Authors: Hiromasa Endo Kanako Takayama Kenji Mitsudo Tatsuya Nakamura Ichiro Seto Hisashi Yamaguchi Takashi Ono Motohisa Suzuki Yusuke Azami Hitoshi Wada Masao Murakami Iwai Tohnai Tags: Article Source Type: research

Cancers, Vol. 10, Pages 330: Proliferative and Invasive Colorectal Tumors in Pet Dogs Provide Unique Insights into Human Colorectal Cancer
Howerth Shaying Zhao Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer model. To better use this resource, we performed an initial global comparison between proliferative and invasive colorectal tumors from 20 canine cases, and evaluated their molecular homology to human colorectal cancer (CRC). First, proliferative canine tumors harbor overactivated WNT/β-catenin pathways and recurrent CTNNB1 (β-catenin) mutations S45F/P, D32Y and G34E. Invasive canine tumors harbor prominent fibroblast proliferation and overactivated stroma. Both groups have recurrent TP53 ...
Source: Cancers - September 14, 2018 Category: Cancer & Oncology Authors: Jin Wang Tianfang Wang Yanfang Sun Yuan Feng William C. Kisseberth Carolyn J. Henry Irene Mok Susan E. Lana Kevin Dobbin Nicole Northrup Elizabeth W. Howerth Shaying Zhao Tags: Article Source Type: research

Cancers, Vol. 10, Pages 331: TRPC6 Channels Are Required for Proliferation, Migration and Invasion of Breast Cancer Cell Lines by Modulation of Orai1 and Orai3 Surface Exposure
i Juan A. Rosado Transient receptor potential channels convey signaling information from a number of stimuli to a wide variety of cellular functions, mainly by inducing changes in cytosolic Ca2+ concentration. Different members of the TRPC, TRPM and TRPV subfamilies have been reported to play a role in tumorigenesis. Here we show that the estrogen receptor positive and triple negative breast cancer cell lines, MCF7 and MDA-MB-231, respectively, exhibit enhanced expression of the TRPC6 channel as compared to the non-tumoral MCF10A cell line. In vitro TRPC6 knockdown using shRNA impaired MCF7 and MDA-MB-231 cell prolif...
Source: Cancers - September 14, 2018 Category: Cancer & Oncology Authors: Isaac Jardin Raquel Diez-Bello Jose J. Lopez Pedro C. Redondo Gin és M. Salido Tarik Smani Juan A. Rosado Tags: Article Source Type: research

Cancers, Vol. 10, Pages 332: Clonal Heterogeneity Reflected by PI3K-AKT-mTOR Signaling in Human Acute Myeloid Leukemia Cells and Its Association with Adverse Prognosis
ash;ystein Bruserud Clonal heterogeneity detected by karyotyping is a biomarker associated with adverse prognosis in acute myeloid leukemia (AML). Constitutive activation of the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in AML cells, and this pathway integrates signaling from several upstream receptors/mediators. We suggest that this pathway reflects biologically important clonal heterogeneity. We investigated constitutive PI3K-Akt-mTOR pathway activation in primary human AML cells derived from 114 patients, together with 18 pathway mediators. The cohort includ...
Source: Cancers - September 14, 2018 Category: Cancer & Oncology Authors: Ina Nepstad Kimberley Joanne Hatfield Tor Henrik Anderson Tvedt H åkon Reikvam Øystein Bruserud Tags: Article Source Type: research

Cancers, Vol. 10, Pages 329: Repurposing of Drugs Targeting YAP-TEAD Functions
or Maria Paola Costi Drug repurposing is a fast and consolidated approach for the research of new active compounds bypassing the long streamline of the drug discovery process. Several drugs in clinical practice have been reported for modulating the major Hippo pathway’s terminal effectors, namely YAP (Yes1-associated protein), TAZ (transcriptional co-activator with PDZ-binding motif) and TEAD (transcriptional enhanced associate domains), which are directly involved in the regulation of cell growth and tissue homeostasis. Since this pathway is known to have many cross-talking phenomena with cell signalin...
Source: Cancers - September 14, 2018 Category: Cancer & Oncology Authors: Gian Marco Elisi Matteo Santucci Domenico D ’Arca Angela Lauriola Gaetano Marverti Lorena Losi Laura Scalvini Maria Laura Bolognesi Marco Mor Maria Paola Costi Tags: Review Source Type: research

Cancers, Vol. 10, Pages 326: Chromogenic Multiplex Immunohistochemistry Reveals Modulation of the Immune Microenvironment Associated with Survival in Elderly Patients with Lung Adenocarcinoma
Hugo Marquette Jean-François Pomerol Gilles Erb Véronique Hofman Paul Hofman With underrepresentation of elderly patients with lung adenocarcinoma (LADC) in anti-PD-1/PD-L1 clinical trials, better understanding of the interplay of PD-L1 and tumor-associated immune cells (TAICs) could assist clinicians in stratifying these patients for immunotherapy. One hundred and one patients with LADCs, stratified by age, were included for analysis of PD-L1 expression and density of TAICs expressing CD4, CD8, and CD33, by using multiplex chromogenic immunohistochemistry (IHC) assays and automated digital quanti...
Source: Cancers - September 13, 2018 Category: Cancer & Oncology Authors: Marius Ili é M élanie Beaulande Saima Ben Hadj Emmanuel Chamorey Renaud Schiappa Elodie Long-Mira Sandra Lassalle Catherine Butori Charlotte Cohen Sylvie Leroy Olivier Gu érin J érôme Mouroux Charles-Hugo Marquette Jean-Fran çois Pomerol Gilles Erb Tags: Article Source Type: research

Cancers, Vol. 10, Pages 327: The Role of Signal Transducer and Activator of Transcription 3 (STAT3) and Its Targeted Inhibition in Hematological Malignancies
tam Sethi Signal transducer and activator of transcription 3 (STAT3), a member of the STAT protein family, can be phosphorylated by receptor-associated Janus kinases (JAKs) in response to stimulation by cytokines and growth factors. It forms homo- or heterodimers that can translocate to the cell nucleus where they act as transcription activators. Constitutive activation of STAT3 has been found to be associated with initiation and progression of various cancers. It can exert proliferative as well as anti-apoptotic effects. This review focuses on the role of STAT3 in pathogenesis i.e., proliferation, differentiation, mig...
Source: Cancers - September 13, 2018 Category: Cancer & Oncology Authors: Loukik Arora Alan Prem Kumar Frank Arfuso Wee Joo Chng Gautam Sethi Tags: Review Source Type: research

Cancers, Vol. 10, Pages 328: Clinical Impact of Epithelial-to-Mesenchymal Transition Regulating MicroRNAs in Pancreatic Ductal Adenocarcinoma
In conclusion, EMT-regulating microRNAs have great potential as liquid and solid biopsy markers in PDAC patients. Their prognostic and therapeutic benefits remain important tasks for future studies. (Source: Cancers)
Source: Cancers - September 13, 2018 Category: Cancer & Oncology Authors: Sameer Abdallah Dhayat Max Michael Traeger Jan Rehkaemper Anda Jana Stroese Konrad Steinestel Eva Wardelmann Iyad Kabar Norbert Senninger Tags: Article Source Type: research

Cancers, Vol. 10, Pages 325: G9a Correlates with VLA-4 Integrin and Influences the Migration of Childhood Acute Lymphoblastic Leukemia Cells
We report here, for the first time, that the expression of G9a (a histone methyltransferase related with gene silencing) correlates with the expression of the integrin subunit α4 in children with ALL. We have demonstrated that G9a depletion or its inhibition with BIX01294 abrogated the ability of ALL cells to migrate through an endothelial monolayer. Moreover, G9a-depleted and BIX01294-treated cells presented bigger nuclei and more adherent phenotype than control cells on endothelial monolayers. Blocking G9a did not affect the cell cytoskeleton or integrin expression of ALL cell lines, and only its depletion ...
Source: Cancers - September 12, 2018 Category: Cancer & Oncology Authors: Elena Madrazo David Ruano Lorea Abad Estefan ía Alonso-Gómez Carmen S ánchez-Valdepeñas África González-Murillo Manuel Ram írez Javier Redondo-Mu ñoz Tags: Article Source Type: research

Cancers, Vol. 10, Pages 324: No Increase in Colon Cancer Risk Following Induction with Neu5Gc-Bearing Rabbit Anti-T Cell IgG (ATG) in Recipients of Kidney Transplants
Gerhard Opelz Because of a mutation of the gene allowing the synthesis of the Neu5Gc form of neuraminidic acid, humans lack the Neu5Gc present in other mammals and develop anti-Neu5Gc. However, humans can absorb dietary Neu5Gc and normal colon epithelium displays minute amounts of Neu5Gc. The potential “physiological” formation of in situ immune complexes has been proposed as a risk factor for colon cancer and as the link between red meat-rich diet and colon carcinoma. In this article, we took advantage of evidence that polyclonal rabbit IgG (ATG) elicits an immune response against Neu5Gc an...
Source: Cancers - September 12, 2018 Category: Cancer & Oncology Authors: Jean-Paul Soulillou Caner S üsal Bernd D öhler Gerhard Opelz Tags: Perspective Source Type: research

Cancers, Vol. 10, Pages 323: CAR-T Cells Based on Novel BCMA Monoclonal Antibody Block Multiple Myeloma Cell Growth
un Wu Vita Golubovskaya The cell-surface protein B cell maturation antigen (BCMA, CD269) has emerged as a promising target for CAR-T cell therapy for multiple myeloma. In order to create a novel BCMA CAR, we generated a new BCMA monoclonal antibody, clone 4C8A. This antibody exhibited strong and selective binding to human BCMA. BCMA CAR-T cells containing the 4C8A scFv were readily detected with recombinant BCMA protein by flow cytometry. The cells were cytolytic for RPMI8226, H929, and MM1S multiple myeloma cells and secreted high levels of IFN-γ in vitro. BCMA-dependent cytotoxicity and IFN-&g...
Source: Cancers - September 11, 2018 Category: Cancer & Oncology Authors: Robert Berahovich Hua Zhou Shirley Xu Yuehua Wei Jasper Guan Jian Guan Hizkia Harto Shuxiang Fu Kaihuai Yang Shuying Zhu Le Li Lijun Wu Vita Golubovskaya Tags: Article Source Type: research

Cancers, Vol. 10, Pages 320: Melatonin Sensitizes Hepatocellular Carcinoma Cells to Chemotherapy Through Long Non-Coding RNA RAD51-AS1-Mediated Suppression of DNA Repair
In this study, we examined the anti-HCC effects of melatonin and elucidated the regulatory mechanisms. The results of functional assays showed that in addition to inhibiting the proliferation, migration, and invasion abilities of HCC cells, melatonin suppressed their DNA repair capacity, thereby promoting the cytotoxicity of chemotherapy and radiotherapy. Whole-transcriptome and gain- and loss-of-function analyses revealed that melatonin induces expression of the long noncoding RNA RAD51-AS1, which binds to RAD51 mRNA to inhibit its translation, effectively decreasing the DNA repair capacity of HCC cells and increasing the...
Source: Cancers - September 10, 2018 Category: Cancer & Oncology Authors: Chin-Chuan Chen Chi-Yuan Chen Shu-Huei Wang Chau-Ting Yeh Shih-Chi Su Shir-Hwa Ueng Wen-Yu Chuang Chuen Hsueh Tong-Hong Wang Tags: Article Source Type: research

Cancers, Vol. 10, Pages 321: miR-9-5p in Nephrectomy Specimens is a Potential Predictor of Primary Resistance to First-Line Treatment with Tyrosine Kinase Inhibitors in Patients with Metastatic Renal Cell Carcinoma
nika Fendler Klaus Jung Approximately 20–30% of patients with metastatic renal cell carcinoma (mRCC) in first-line treatment with tyrosine kinase inhibitors (TKIs) do not respond due to primary resistance to this drug. At present, suitable robust biomarkers for prediction of a response are not available. Therefore, the aim of this study was to evaluate a panel of microRNAs (miRNAs) in nephrectomy specimens for use as predictive biomarkers for TKI resistance. Archived formalin-fixed, paraffin embedded nephrectomy samples from 60 mRCC patients treated with first-line TKIs (sunitinib, n = 51; pazopanib, n ...
Source: Cancers - September 10, 2018 Category: Cancer & Oncology Authors: Bernhard Ralla Jonas Busch Anne Fl örcken J örg Westermann Zhongwei Zhao Ergin Kilic Sabine Weickmann Monika Jung Annika Fendler Klaus Jung Tags: Article Source Type: research

Cancers, Vol. 10, Pages 322: High-Dose-Rate Brachytherapy Monotherapy versus Image-Guided Intensity-Modulated Radiotherapy with Helical Tomotherapy for Patients with Localized Prostate Cancer
We examined 353 HDR-BT and 270 IG-IMRT patients. To reduce background selection bias, we used the method of inverse probability treatment weighting (IPTW) with propensity scores. The actuarial five-year biochemical failure-free survival rates were 92.9% and 96.7% (p = 0.1847; p = 0.077 in IPTW) for HDR-BT and IG-IMRT, respectively; they were 100% and 95.8% (p = 0.286) for the low-risk group, 95.6% and 92% (p = 0.42) for the intermediate-risk group, 90.4% and 84.9% (p = 0.1059; p = 0.04 in IPTW) for the high-risk group, and 87.1% and 89.2% (p = 0.3816) for the very-high-risk group. In the assessment of accumulated incidence...
Source: Cancers - September 10, 2018 Category: Cancer & Oncology Authors: Hideya Yamazaki Koji Masui Gen Suzuki Satoaki Nakamura Daisuke Shimizu Tatsuyuki Nishikawa Haruumi Okabe Ken Yoshida Tadayuki Kotsuma Eiichi Tanaka Keisuke Otani Yasuo Yoshioka Kazuhiko Ogawa Tags: Article Source Type: research

Cancers, Vol. 10, Pages 319: Impact of Tumor Regression Grade as a Major Prognostic Factor in Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiotherapy: A Proposal for a Modified Staging System
In conclusion, a GR to neoadjuvant CRT is an independent predictor of good DFS and overall survival and further stratifies patients so as to estimate the risk of recurrence and survival among patients with ypStage II and III rectal cancer. (Source: Cancers)
Source: Cancers - September 7, 2018 Category: Cancer & Oncology Authors: Changhoon Song Joo-Hyun Chung Sung-Bum Kang Duck-Woo Kim Heung-Kwon Oh Hye Seung Lee Jin Won Kim Keun-Wook Lee Jee Hyun Kim Jae-Sung Kim Tags: Article Source Type: research

Cancers, Vol. 10, Pages 318: Nutrition Impact Symptoms Are Prognostic of Quality of Life and Mortality after Surgery for Oesophageal Cancer
la Lagergren We aimed to clarify the influence of nutritional problems after surgery for oesophageal cancer on functional health related quality of life (HRQOL) and survival. A prospective nationwide cohort of oesophageal cancer patients operated 2001–2005 in Sweden with 6 months postoperative follow up was used. Nutritional problems were categorized as low/moderate/severe/very severe based on weight loss and nutrition impact symptoms. An ANCOVA model calculated mean score differences (MD) with 95% confidence intervals (CI) of global quality of life (QOL), social and physical function scores, stratified by preope...
Source: Cancers - September 7, 2018 Category: Cancer & Oncology Authors: Poorna Anandavadivelan Lena Martin Therese Dj ärv Asif Johar Pernilla Lagergren Tags: Article Source Type: research

Cancers, Vol. 10, Pages 317: Transcriptome Signatures of Canine Mammary Gland Tumors and Its Comparison to Human Breast Cancers
-Yoel Cho Breast cancer (BC)/mammary gland carcinoma (MGC) is the most frequently diagnosed and leading cause of cancer-related mortality in both women and canines. To better understand both canine MGC and human BC-specific genes, we sequenced RNAs obtained from eight pairs of carcinomas and adjacent normal tissues in dogs. By comprehensive transcriptome analysis, 351 differentially expressed genes (DEGs) were identified in overall canine MGCs. Based on the DEGs, comparative analysis revealed correlation existing among the three histological subtypes of canine MGC (ductal, simple, and complex) and four molecular subtyp...
Source: Cancers - September 7, 2018 Category: Cancer & Oncology Authors: Kang-Hoon Lee Hyoung-Min Park Keun-Hong Son Tae-Jin Shin Je-Yoel Cho Tags: Article Source Type: research

Cancers, Vol. 10, Pages 314: PTPRT and PTPRD Deleterious Mutations and Deletion Predict Bevacizumab Resistance in Metastatic Colorectal Cancer Patients
Conclusion: Deleterious alterations in PTPRT/PTPRD are potential biomarkers for bevacizumab resistance. (Source: Cancers)
Source: Cancers - September 6, 2018 Category: Cancer & Oncology Authors: Hung-Chih Hsu Nina Lapke Shu-Jen Chen Yen-Jung Lu Ren-Shiang Jhou Chien-Yuh Yeh Wen-Sy Tsai Hsin-Yuan Hung Jason Chia-Hsun Hsieh Tsai-Sheng Yang Tan Kien Thiam Jeng-Fu You Tags: Article Source Type: research

Cancers, Vol. 10, Pages 315: Could miRNA Signatures be Useful for Predicting Uterine Sarcoma and Carcinosarcoma Prognosis and Treatment?
This study aimed to assess the expression profile of 84 cancer-related miRNAs and to evaluate their correlation with clinical pathological features. Eighty-two formalin-fixed paraffin-embedded (FFPE) samples were selected. In leiomyosarcoma (LMS), there was an association of lower cancer-specific survival (CSS) with the downregulation of miR-125a-5p and miR-10a-5p, and the upregulation of miR-196a-5p and miR-34c-5p. In carcinosarcoma (CS), lower CSS was associated with the upregulation of miR-184, and the downregulation of let-7b-5p and miR-124. In endometrial stromal sarcomas (ESS), the upregulation of miR-373-3p, miR-372...
Source: Cancers - September 6, 2018 Category: Cancer & Oncology Authors: Laura Gonzalez dos Anjos Bruna Cristine de Almeida Thais Gomes de Almeida Andr é Mourão Lavorato Rocha Giovana De Nardo Maffazioli Fernando Augusto Soares Isabela Werneck da Cunha Edmund Chada Baracat Katia Candido Carvalho Tags: Article Source Type: research

Cancers, Vol. 10, Pages 316: The Extracellular Matrix and Pancreatic Cancer: A Complex Relationship
Liss Pancreatic ductal adenocarcinoma (PDAC) has an extraordinarily dense fibrotic stroma that impedes tumor perfusion and delivery of anticancer drugs. Since the extracellular matrix (ECM) comprises the bulk of the stroma, it is primarily responsible for the increased interstitial tissue pressure and stiff mechanical properties of the stroma. Besides its mechanical influence, the ECM provides important biochemical and physical cues that promote survival, proliferation, and metastasis. By serving as a nutritional source, the ECM also enables PDAC cells to survive under the nutrient-poor conditions. While therapeutic s...
Source: Cancers - September 6, 2018 Category: Cancer & Oncology Authors: Maximilian Weniger Kim C. Honselmann Andrew S. Liss Tags: Review Source Type: research

Cancers, Vol. 10, Pages 313: Non-Invasive Assessment of Lactate Production and Compartmentalization in Renal Cell Carcinomas Using Hyperpolarized 13C Pyruvate MRI
Larson Zhen J. Wang Optimal treatment selection for localized renal tumors is challenging due to their variable biological behavior and limited ability to pre-operatively assess their aggressiveness. We investigated hyperpolarized (HP) 13C pyruvate MRI to noninvasively assess tumor lactate production and compartmentalization, which are strongly associated with renal tumor aggressiveness. Orthotopic tumors were created in mice using human renal cell carcinoma (RCC) lines (A498, 786-O, UOK262) with varying expression of lactate dehydrogenase A (LDHA) which catalyzes the pyruvate-to-lactate conversion, and varying expre...
Source: Cancers - September 5, 2018 Category: Cancer & Oncology Authors: Renuka Sriram Jeremy Gordon Celine Baligand Fayyaz Ahamed Justin Delos Santos Hecong Qin Robert A. Bok Daniel B. Vigneron John Kurhanewicz Peder E. Z. Larson Zhen J. Wang Tags: Article Source Type: research

Cancers, Vol. 10, Pages 311: Insonation of Systemically Delivered Cisplatin-Loaded Microbubbles Significantly Attenuates Nephrotoxicity of Chemotherapy in Experimental Models of Head and Neck Cancer
iang Chu Chih-Hung Wang The use of cisplatin (CDDP), the most common chemotherapy drug for head and neck cancer, is limited by its undesirable side effects, especially nephrotoxicity. We investigated ultrasound microbubbles (USMB) as a tool to increase the local intra-tumoral CDDP level while decreasing systemic CDDP cytotoxicity. We allowed CDDP to interact with human serum albumin and then sonicated the resulting CDDP‒albumin complex to generate CDDP-loaded MBs (CDDP-MBs). We then established a head-and-neck tumor-bearing mouse model by implanting FaDu-fLuc/GFP cells into severe combined immunodeficiency mice and...
Source: Cancers - September 5, 2018 Category: Cancer & Oncology Authors: Hang-Kang Chen Shu-Mei Zhang Junn-Liang Chang Hsin-Chien Chen Yi-Chun Lin Cheng-Ping Shih Huey-Kang Sytwu Mei-Cho Fang Yuan-Yung Lin Chao-Yin Kuo Ai-Ho Liao Yueng-Hsiang Chu Chih-Hung Wang Tags: Article Source Type: research

Cancers, Vol. 10, Pages 312: Serial MRI Imaging Reveals Minimal Impact of Ketogenic Diet on Established Liver Tumor Growth
Kyle L. Hoehn Rodent models of liver tumorigenesis have reproducibly shown that dietary sugar intake is a powerful driver of liver tumor initiation and growth. In contrast, dietary sugar restriction with ketogenic diets or calorie restriction generally prevents liver tumor formation. Ketogenic diet is viewed positively as a therapeutic adjuvant; however, most ketogenic diet studies described to date have been performed in prevention mode rather than treatment mode. Therefore, it remains unclear whether a ketogenic diet can be administered in late stages of disease to stall or reverse liver tumor growth. To model the cl...
Source: Cancers - September 5, 2018 Category: Cancer & Oncology Authors: Frances L. Byrne Stefan R. Hargett Sujoy Lahiri R. Jack Roy Stuart S. Berr Stephen H. Caldwell Kyle L. Hoehn Tags: Brief Report Source Type: research

Cancers, Vol. 10, Pages 306: Targeting Raf Kinase Inhibitory Protein Regulation and Function
ner Raf Kinase Inhibitory Protein (RKIP) is a highly conserved kinase inhibitor that functions as a metastasis suppressor in a variety of cancers. Since RKIP can reprogram tumor cells to a non-metastatic state by rewiring kinase networks, elucidating the mechanism by which RKIP acts not only reveals molecular mechanisms that regulate metastasis, but also represents an opportunity to target these signaling networks therapeutically. Although RKIP is often lost during metastatic progression, the mechanism by which this occurs in tumor cells is complex and not well understood. In this review, we summarize our current under...
Source: Cancers - September 4, 2018 Category: Cancer & Oncology Authors: Ali Ekrem Yesilkanal Marsha Rich Rosner Tags: Review Source Type: research

Cancers, Vol. 10, Pages 307: A Comprehensive Survey of Immune Cytolytic Activity-Associated Gene Co-Expression Networks across 17 Tumor and Normal Tissue Types
Song Zhi Wei Cytolytic immune activity in solid tissue can be quantified by transcript levels of two genes, GZMA and PRF1, which is named the CYT score. A previous study has investigated the molecular and genetic properties of tumors associated CYT, but a systematic exploration of how co-expression networks across different tumors are shaped by anti-tumor immunity is lacking. Here, we examined the connectivity and biological themes of CYT-associated modules in gene co-expression networks of 14 tumor and 3 matched normal tissues constructed from the RNA-Seq data of the “The Cancer Genome Atlas&r...
Source: Cancers - September 4, 2018 Category: Cancer & Oncology Authors: Tian Tian Ji Wan Yan Han Haoran Liu Feng Gao Youdong Pan Qi Song Zhi Wei Tags: Article Source Type: research

Cancers, Vol. 10, Pages 308: Cariprazine, A Dopamine D2/D3 Receptor Partial Agonist, Modulates ABCG2-Mediated Multidrug Resistance in Cancer
Amit K. Tiwari Multidrug resistance (MDR) is a continuing clinical problem that limits the efficacy of chemotherapy in cancer. The over expression of the ATP-binding cassette (ABC) family G2 (ABCG2) transporter is one of the main mechanisms that mediates MDR in cancer. Molecular modeling data indicated that cariprazine, a dopamine D2/D3 receptor partial agonist, had a significant binding affinity for ABCG2 transporter with a Glide XP score of −6.515. Therefore, in this in vitro study, we determined the effect of cariprazine on MDR resulting from the overexpression of ABCG2 transporters. Alone, cariprazin...
Source: Cancers - September 4, 2018 Category: Cancer & Oncology Authors: Noor Hussein Charles R. Ashby Haneen Amawi Angelique Nyinawabera Atul Vij Vishwa M. Khare Chandrabose Karthikeyan Amit K. Tiwari Tags: Article Source Type: research

Cancers, Vol. 10, Pages 309: A Dietary Intervention to Lower Serum Levels of IGF-I in BRCA Mutation Carriers
Conclusions: Women in the intervention group showed significant improvements in IGF-I and in other IRm that might influence the penetrance of BRCA mutations. (Source: Cancers)
Source: Cancers - September 4, 2018 Category: Cancer & Oncology Authors: Patrizia Pasanisi Eleonora Bruno Elisabetta Venturelli Daniele Morelli Andreina Oliverio Ivan Baldassari Francesca Rovera Giovanna Iula Monica Taborelli Bernard Peissel Jacopo Azzolini Siranoush Manoukian Tags: Article Source Type: research

Cancers, Vol. 10, Pages 310: Surgical Resection Versus Stereotactic Body Radiation Therapy for Stage I NSCLC: Can Randomized Trials Provide the Solution?
ers Surgical resection has traditionally been considered the standard of care for patients with stage I non-small cell lung cancer (NSCLC). With the introduction of stereotactic radiation body therapy (SBRT), there is now a viable option for medically inoperable patients with stage I NSCLC. The effectiveness of SBRT in patients with stage I disease but at elevated surgical risk is unknown. Multiple randomized controlled trials (RCTs) have been attempted to compare surgical resection and SBRT in this population, but have been aborted due to poor patient enrollment. Despite these failures, there still remains a push for ...
Source: Cancers - September 4, 2018 Category: Cancer & Oncology Authors: Melanie P. Subramanian Bryan F. Meyers Tags: Perspective Source Type: research

Cancers, Vol. 10, Pages 304: Classic Hodgkin Lymphoproliferative Diseases Clonally Unrelated to B-Chronic Lymphocytic Leukemia Successfully Treated with Bendamustine Plus Rituximab
Nakamura Itaru Matsumura A 62-year-old male was diagnosed with chronic lymphocytic leukemia (CLL) and treated with a fludarabine-containing regimen which maintained the disease in a partial response. Nine years after diagnosis, a rapidly growing systemic lymphadenopathy was observed, and a biopsy specimen revealed the presence of typical Hodgkin/Reed-Sternberg (HRS) cells, surrounded by T-lymphocytes and CLL cells. Sequencing analysis of the germline complementary determining region 3 (CDR3) region of the immunoglobulin heavy chain (IGH) gene showed that the Hodgkin/Reed-Sternberg cells were clonally unrelated to th...
Source: Cancers - September 3, 2018 Category: Cancer & Oncology Authors: Shinya Rai Hirokazu Tanaka Ko Fujimoto Takahiro Kumode Hiroaki Inoue Yasuhiro Taniguchi Yasuyoshi Morita J. Luis Espinoza Yoichi Tatsumi Takashi Ashida Ryota Matsuoka Yukie Yara Kikuti Naoya Nakamura Itaru Matsumura Tags: Case Report Source Type: research

Cancers, Vol. 10, Pages 305: Peroxiredoxin II Regulates Cancer Stem Cells and Stemness-Associated Properties of Cancers
Kwon Cancer stem cells (CSCs) represent a sub-population of cancer cells with the ability to regulate stemness-associated properties which are specifically responsible for unlimited growth of cancers, generation of diverse cancer cells in differentiated state and resistance to existing chemotherapy and radiotherapy. Even though, current therapies destroy majority of cancer cells, it is believed to leave CSCs without eradicating which may be the conceptualization for chemoresistance and radio-resistance. Reactive oxygen species (ROS) maintain stem cells and regulate the stemness-associated properties of cancers. Beyond...
Source: Cancers - September 3, 2018 Category: Cancer & Oncology Authors: Nisansala Chandimali Dong Kee Jeong Taeho Kwon Tags: Review Source Type: research

Cancers, Vol. 10, Pages 296: Heated Intraperitoneal Chemotherapy in the Management of Advanced Ovarian Cancer
abele Heated intraperitoneal chemotherapy (HIPEC) has several potential benefits. Higher doses of chemotherapy can be used with HIPEC because the plasma-peritoneal barrier results in little absorption into the blood stream. HIPEC offers higher peritoneal penetration in comparison to an intravenous (IV) regimen and does not have the traditional normothermic intraperitoneal (IP) regimen limitation of post-operative adhesions. Hyperthermia itself has cytotoxic effects and can potentiate antineoplastic effects of chemotherapy in part by increasing the depth of tumor penetration by up to 3 mm. For the treatment of ovarian c...
Source: Cancers - September 1, 2018 Category: Cancer & Oncology Authors: Andrea Jewell Megan McMahon Dineo Khabele Tags: Review Source Type: research

Cancers, Vol. 10, Pages 297: The p53 Pathway in Glioblastoma
Fang Yuan Roger Abounader The tumor suppressor and transcription factor p53 plays critical roles in tumor prevention by orchestrating a wide variety of cellular responses, including damaged cell apoptosis, maintenance of genomic stability, inhibition of angiogenesis, and regulation of cell metabolism and tumor microenvironment. TP53 is one of the most commonly deregulated genes in cancer. The p53-ARF-MDM2 pathway is deregulated in 84% of glioblastoma (GBM) patients and 94% of GBM cell lines. Deregulated p53 pathway components have been implicated in GBM cell invasion, migration, proliferation, evasion of apoptosis, a...
Source: Cancers - September 1, 2018 Category: Cancer & Oncology Authors: Ying Zhang Collin Dube Myron Gibert Nichola Cruickshanks Baomin Wang Maeve Coughlan Yanzhi Yang Initha Setiady Ciana Deveau Karim Saoud Cassandra Grello Madison Oxford Fang Yuan Roger Abounader Tags: Review Source Type: research

Cancers, Vol. 10, Pages 298: Rare Genetic Diseases with Defects in DNA Repair: Opportunities and Challenges in Orphan Drug Development for Targeted Cancer Therapy
ndi A better understanding of mechanistic insights into genes and enzymes implicated in rare diseases provide a unique opportunity for orphan drug development. Advances made in identification of synthetic lethal relationships between rare disorder genes with oncogenes and tumor suppressor genes have brought in new anticancer therapeutic opportunities. Additionally, the rapid development of small molecule inhibitors against enzymes that participate in DNA damage response and repair has been a successful strategy for targeted cancer therapeutics. Here, we discuss the recent advances in our understanding of how many rare ...
Source: Cancers - September 1, 2018 Category: Cancer & Oncology Authors: Sonali Bhattacharjee Saikat Nandi Tags: Review Source Type: research

Cancers, Vol. 10, Pages 299: Metabolic Syndrome and the Risk of Breast Cancer and Subtypes by Race, Menopause and BMI
The objective of this study was to investigate the association of metabolic syndrome (MetS) with the risk of invasive breast cancer and molecular subtypes across race, menopause, and body mass index (BMI) groups. We examined the association of metabolic syndrome and its components with risk of invasive breast cancer among 94,555 female participants of the National Institute of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, accounting for ductal carcinoma in situ as a competing risk. Cox proportional hazard regression with the Fine and Gray method was used to generate hazard ratios (HR) and...
Source: Cancers - September 1, 2018 Category: Cancer & Oncology Authors: Daniel T. Dibaba Dejana Braithwaite Tomi Akinyemiju Tags: Article Source Type: research

Cancers, Vol. 10, Pages 300: Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive Candidate Markers for Colorectal Cancer
ndina Juan M. Falcón-Pérez Low invasive tests with high sensitivity for colorectal cancer and advanced precancerous lesions will increase adherence rates, and improve clinical outcomes. We have performed an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-(TOF) MS)-based metabolomics study to identify faecal biomarkers for the detection of patients with advanced neoplasia. A cohort of 80 patients with advanced neoplasia (40 advanced adenomas and 40 colorectal cancers) and 49 healthy subjects were analysed in the study. We evaluated the faecal levels of 105 metabolites inclu...
Source: Cancers - September 1, 2018 Category: Cancer & Oncology Authors: Joaquin Cubiella Marc Clos-Garcia Cristina Alonso Ibon Martinez-Arranz Miriam Perez-Cormenzana Ziortza Barrenetxea Jesus Berganza Isabel Rodr íguez-Llopis Mauro D ’Amato Luis Bujanda Marta Diaz-Ondina Juan M. Falc ón-Pérez Tags: Article Source Type: research