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Frontiers in Oncology

Chiemi Saigo, Yusuke Kito, Tamotsu Takeuchi
Recent findings indicate that the WW domain-containing oxidoreductase (WWOX) is a tumor suppressor protein that contains two N-terminal WW domains and a central short-chain dehydrogenase/reductase domain. WWOX protein mediates multiple signaling networks that suppress carcinogenesis through binding of its first WW domain to various cancer-associated proteins, i.e., p73, AP-2γ, and others. Although the tumor suppressor property of WWOX is inarguable, WWOX is not inactivated in the manner characteristic of the canonical Knudson hypothesis...
2018: Frontiers in Oncology
Nemanja Rajković, Xingyu Li, Konstantinos N Plataniotis, Ksenija Kanjer, Marko Radulovic, Nebojša T Milošević
Improved prognosis of breast cancer outcome could prolong patient survival by reliable identification of patients at high risk of metastasis occurrence which could benefit from more aggressive treatments. Based on such clinical need, we prognostically evaluated the malignant cells in breast tumors, as the obvious potential source of unexploited prognostic information. The patient group was homogeneous, without any systemic treatments or lymph node spread, with smaller tumor size (pT1/2) and a long follow-up...
2018: Frontiers in Oncology
Hisham F Bahmad, Katia Cheaito, Reda M Chalhoub, Ola Hadadeh, Alissar Monzer, Farah Ballout, Albert El-Hajj, Deborah Mukherji, Yen-Nien Liu, Georges Daoud, Wassim Abou-Kheir
Cancer Stem Cells (CSCs) are a sub-population of cells, identified in most tumors, responsible for the initiation, recurrence, metastatic potential, and resistance of different malignancies. In prostate cancer (PCa), CSCs were identified and thought to be responsible for the generation of the lethal subtype, commonly known as Castration-Resistant Prostate Cancer (CRPC). In vitro models to investigate the properties of CSCs in PCa are highly required. Sphere-formation assay is an in vitro method commonly used to identify CSCs and study their properties...
2018: Frontiers in Oncology
Karolina Pospiech, Elzbieta Płuciennik, Andrzej K Bednarek
The WWOX tumor suppressor gene is located at 16q23. 1-23.2, which covers the region of FRA16D-a common fragile sites. Deletions within the WWOX coding sequence are observed in up to 80% of breast cancer cases, which makes it one of the most common genetic alterations in this tumor type. The WWOX gene is known to play a role in breast cancer: increased expression of WWOX inhibits cell proliferation in suspension, reduces tumor growth rates in xenographic transplants, but also enhances cell migration through the basal membrane and contributes to morphological changes in 3D matrix-based cell cultures...
2018: Frontiers in Oncology
Patries M Herst, Rebecca H Dawson, Michael V Berridge
Intercellular communication between cancer cells and other cells in the tumor microenvironment plays a defining role in tumor development. Tumors contain infiltrates of stromal cells and immune cells that can either promote or inhibit tumor growth, depending on the cytokine/chemokine milieu of the tumor microenvironment and their effect on cell activation status. Recent research has shown that stromal cells can also affect tumor growth through the donation of mitochondria to respiration-deficient tumor cells, restoring normal respiration...
2018: Frontiers in Oncology
Marieke Bamps, Rüveyda Dok, Sandra Nuyts
Objectives: Low-level laser therapy (LLLT) is a promising non-invasive treatment option for oropharyngeal mucositis, which is a common side effect of many oncological treatments. LLLT is known for its wound healing properties due to the stimulation of cellular processes, such as proliferation, migration and differentiation. Controversy exists on the possible stimulatory effect of LLLT on head and neck cancer (HNSCC) cells in patients treated with radiotherapy. The aim of this study was to evaluate the biostimulatory effect together with the underlying mechanisms of LLLT on HNSCC cancer cells and normal epithelial cells...
2018: Frontiers in Oncology
Teresa Y Lee, Ubaldo E Martinez-Outschoorn, Russell J Schilder, Christine H Kim, Scott D Richard, Norman G Rosenblum, Jennifer M Johnson
Endometrial cancer is the most common gynecologic malignancy in developed countries. Its increasing incidence is thought to be related in part to the rise of metabolic syndrome, which has been shown to be a risk factor for the development of hyperestrogenic and hyperinsulinemic states. This has consequently lead to an increase in other hormone-responsive cancers as well e.g., breast and ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial cancer has highlighted the important role of metabolism in cancer establishment and persistence...
2018: Frontiers in Oncology
John G Clohessy, Pier Paolo Pandolfi
Precision medicine holds real promise for the treatment of cancer. Adapting therapeutic strategies so patients receive individualized treatment protocols, will transform how diseases like cancer are managed. Already, molecular profiling technologies have provided unprecedented capacity to characterize tumors, yet the ability to translate this to actionable outcome in the clinic is limited. To enable real time translation of personalized therapeutic approaches to patient care in a co-clinical manner will require the adoption and integration of approaches that facilitate modeling of patient disease...
2018: Frontiers in Oncology
Tomohiro Enokida, Susumu Okano, Takao Fujisawa, Yuri Ueda, Shinya Uozumi, Makoto Tahara
Purpose: We sought to evaluate the efficacy and safety of the combination of cetuximab (Cmab) and paclitaxel (PTX) in patients with squamous cell carcinoma of the head and neck (SCCHN) who had unresectable recurrent or metastatic (R/M) disease after platinum-based chemoradiotherapy. Materials and Methods: Data on 23 patients with SCCHN who received paclitaxel and cetuximab (Cmab) for R/M disease no more than 6 months after CRT completion were retrospectively reviewed. PTX and Cmab were given in a 28-day cycle (PTX, 80 mg/m2 on days 1, 8, and 15; Cmab, loading dose 400 mg/m2 followed by a weekly 250 mg/m2 )...
2018: Frontiers in Oncology
Ying Meng, Suganth Suppiah, Shanan Surendrakumar, Luca Bigioni, Nir Lipsman
Low-intensity MR-guided focused ultrasound in combination with intravenously injected microbubbles is a promising platform for drug delivery to the central nervous system past the blood-brain barrier. The blood-brain barrier is a key bottleneck for cancer therapeutics via limited inter- and intracellular transport. Further, drugs that cross the blood-brain barrier when delivered in a spatially nonspecific way, result in adverse effects on normal brain tissue, or at high concentrations, result in increasing risks to peripheral organs...
2018: Frontiers in Oncology
Patrick Weyerhäuser, Sven R Kantelhardt, Ella L Kim
There is a growing evidence that antimalarial chloroquine could be re-purposed for cancer treatment. A dozen of clinical trials have been initiated within the past 10 years to test the potential of chloroquine as an adjuvant treatment for therapy-refractory cancers including glioblastoma, one of the most aggressive human cancers. While there is considerable evidence for the efficacy and safety of chloroquine the mechanisms underlying the tumor suppressive actions of this drug remain elusive. Up until recently, inhibition of the late stage of autophagy was thought to be the major mechanism of chloroquine-mediated cancer cells death...
2018: Frontiers in Oncology
Fabio Corrà, Chiara Agnoletto, Linda Minotti, Federica Baldassari, Stefano Volinia
Non-coding RNAs (ncRNAs) have been implicated in most cellular functions. The disruption of their function through somatic mutations, genomic imprinting, transcriptional and post-transcriptional regulation, plays an ever-increasing role in cancer development. ncRNAs, including notorious microRNAs, have been thus proposed to function as tumor suppressors or oncogenes, often in a context-dependent fashion. In parallel, ncRNAs with altered expression in cancer have been reported to exert a key role in determining drug sensitivity or restoring drug responsiveness in resistant cells...
2018: Frontiers in Oncology
Sara Bisetto, Diana Whitaker-Menezes, Nicole A Wilski, Madalina Tuluc, Joseph Curry, Tingting Zhan, Christopher M Snyder, Ubaldo E Martinez-Outschoorn, Nancy J Philp
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common human cancer and affects approximately 50,000 new patients every year in the US. The major risk factors for HNSCC are tobacco and alcohol consumption as well as oncogenic HPV infections. Despite advances in therapy, the overall survival rate for all-comers is only 50%. Understanding the biology of HNSCC is crucial to identifying new biomarkers, implementing early diagnostic approaches and developing novel therapies. As in several other cancers, HNSCC expresses elevated levels of MCT4, a member of the SLC16 family of monocarboxylate transporters...
2018: Frontiers in Oncology
Courtney S Malo, Roman H Khadka, Katayoun Ayasoufi, Fang Jin, Jackson E AbouChehade, Michael J Hansen, Raymond Iezzi, Kevin D Pavelko, Aaron J Johnson
Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median survival rate of 15 months with treatment. Thus, there is a critical need to develop novel therapies for GBM. Immunotherapy is emerging as a promising therapeutic strategy. However, current therapies for GBM, in particular anti-angiogenic therapies that block vascular endothelial growth factor (VEGF), may have undefined consequences on the efficacy of immunotherapy. While this treatment is primarily prescribed to reduce tumor vascularization, multiple immune cell types also express VEGF receptors, including the most potent antigen-presenting cell, the dendritic cell (DC)...
2018: Frontiers in Oncology
Paul D Juarez, Patricia Matthews-Juarez
Traditional research approaches, including genome-wide association studies (GWAS), epigenome-wide association studies (EWAS) and Gene × Environment (G × E) studies are limited in their ability to handle the multiplicity of chemical and non-chemical toxicants to which people are exposed in the real world, over their life course, their impact on epigenomics and other biological systems, and their relationship to cancer onset, progression, and outcomes. Exposome-wide association study (ExWAS) provides a new approach for conceptualizing the roles and relationships of multiple chemical and non-chemical exposures in the etiology and progression of cancer at key developmental periods, over the life course, and across generations...
2018: Frontiers in Oncology
Martin David Forster, Michael-John Devlin
Head and Neck Squamous Cell Carcinoma (HNSCC) is the 6th most common cancer globally and commonly presents with locally advanced disease, which has a recurrence rate of around 50% despite aggressive multi-modality treatment involving surgery, radiotherapy and chemotherapy or EGFR inhibition where appropriate. As understanding of the underlying cancer biology and the complex interactions within the tumor microenvironment improves, there is gathering interest in and evidence for the role of immunomodulating agents in the management of HNSCC...
2018: Frontiers in Oncology
Jingquan Jia, Michael A Morse, Rebecca J Nagy, Richard B Lanman, John H Strickler
MET amplification is rare in treatment-naïve metastatic colorectal cancer (CRC) tumors, but can emerge as a mechanism of resistance to anti-EGFR therapies. Preclinical and clinical data suggest that patients with MET amplified tumors benefit from MET-targeted therapy. Cabozantinib is an inhibitor of multiple tyrosine kinases, included c-MET. Panitumumab is an inhibitor of EGFR. This report describes a patient with KRAS, NRAS , and BRAF wild-type metastatic CRC who experienced disease progression on all standard chemotherapy and anti-EGFR antibody therapy...
2018: Frontiers in Oncology
Giuseppe Cannino, Francesco Ciscato, Ionica Masgras, Carlos Sánchez-Martín, Andrea Rasola
Mitochondria are dynamic organelles that exchange a multiplicity of signals with other cell compartments, in order to finely adjust key biological routines to the fluctuating metabolic needs of the cell. During neoplastic transformation, cells must provide an adequate supply of the anabolic building blocks required to meet a relentless proliferation pressure. This can occur in conditions of inconstant blood perfusion leading to variations in oxygen and nutrient levels. Mitochondria afford the bioenergetic plasticity that allows tumor cells to adapt and thrive in this ever changing and often unfavorable environment...
2018: Frontiers in Oncology
Renzhi Yao, Haifan Zou, Weijia Liao
CircRNA, a kind of tissue specific and covalently closed circular non-coding RNA is very abundant in eukaryocyte. Generally, circRNA is generated by back-splicing of protein-coding genes' pre-mRNA. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Due to the characteristics of poor prognosis and high recurrence, the pathogenesis of HCC is highly concerned by researchers worldwide. Recent studies demonstrated that numerous circRNAs were differentially expressed in HCC tissues and normal liver tissues, which is closely related with the development and prognosis of HCC...
2018: Frontiers in Oncology
Marina Mojena, Adrián Povo-Retana, Silvia González-Ramos, Victoria Fernández-García, Javier Regadera, Arturo Zazpe, Inés Artaiz, Paloma Martín-Sanz, Francisco Ledo, Lisardo Boscá
Melanomas are heterogeneous and aggressive tumors, and one of the worse in prognosis. Melanoma subtypes follow distinct pathways until terminal oncogenic transformation. Here, we have evaluated a series of molecules that exhibit potent cytotoxic effects over the murine and human melanoma cell lines B16F10 and MalMe-3M, respectively, both ex vivo and in animals carrying these melanoma cells. Ex vivo mechanistic studies on molecular targets involved in melanoma growth, migration and viability were evaluated in cultured cells treated with these drugs which exhibited potent proapoptotic and cytotoxic effects and reduced cell migration...
2018: Frontiers in Oncology
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