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Asuka Nanbo, Harutaka Katano, Michiyo Kataoka, Shiho Hoshina, Tsuyoshi Sekizuka, Makoto Kuroda, Yusuke Ohba
Infection of Epstein⁻Barr virus (EBV), a ubiquitous human gamma herpesvirus, is associated with various malignancies in B lymphocytes and epithelial cells. EBV encodes 49 microRNAs in two separated regions, termed the BART and BHRF1 loci. Although accumulating evidence demonstrates that EBV infection regulates the profile of microRNAs in the cells, little is known about the microRNAs in exosomes released from infected cells. Here, we characterized the expression profile of intracellular and exosomal microRNAs in EBV-negative, and two related EBV-infected Burkitt lymphoma cell lines having type I and type III latency by next-generation sequencing...
July 19, 2018: Cancers
Juliet A Carmichael, Daisy Wing-San Mak, Mary O'Brien
Until recently, chemotherapy has remained the mainstay of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC). Excellent responses have been observed with immune-checkpoint inhibitors, and targeted treatments for those tumours with actionable mutations, resulting in a paradigm shift in the treatment approach for these patients. Elderly patients and those with poor performance status (PS), such as Eastern Cooperative Oncology Group (ECOG) 2, have historically been excluded from clinical trials due to poor outcomes...
July 18, 2018: Cancers
Lisa Scarton, Saunjoo Yoon, Sungho Oh, Edward Agyare, Jose Trevino, Bo Han, Eunsook Lee, Veronica Wendy Setiawan, Jennifer B Permuth, Thomas D Schmittgen, Folakemi G Odedina, Diana J Wilkie
We summarize the risk factors that may significantly contribute to racial disparities in pancreatic cancer, which is now the third leading cause of cancer deaths and projected to be second around 2030 in 12 years. For decades, the incidence rate of pancreatic cancer among Blacks has been 30% to 70% higher than other racial groups in the United States and the 5-year survival rate is approximately 5%. Diabetes and obesity have been identified as potentially predisposing factors to pancreatic cancer and both are more common among Blacks...
July 18, 2018: Cancers
Mariafrancesca Cascione, Valeria De Matteis, Chiara C Toma, Stefano Leporatti
The Epithelial to mesenchymal transition (EMT) is the process that drives epithelial tumor cells to acquire an invasive phenotype. The role of transforming growth factor-β1 (TGF-β1) in EMT is still debated. We used confocal laser scanning microscopy and scanning force spectroscopy to perform a morphomechanical analysis on epithelial breast cancer cells (MCF-7), comparing them before and after TGF-β1 exogenous stimulation (5 ng/mL for 48 h). After TGF-β1 treatment, loss of cell⁻cell adherence (mainly due to the reduction of E-cadherin expression of about 24%) and disaggregation of actin cortical fibers were observed in treated MCF-7...
July 16, 2018: Cancers
Corina Cuceu, Bruno Colicchio, Eric Jeandidier, Steffen Junker, François Plassa, Grace Shim, Justyna Mika, Monika Frenzel, Mustafa Al Jawhari, William M Hempel, Grainne O'Brien, Aude Lenain, Luc Morat, Theodore Girinsky, Alain Dieterlen, Joanna Polanska, Christophe Badie, Patrice Carde, Radhia M'Kacher
Background : Microsatellite and chromosomal instability have been investigated in Hodgkin lymphoma (HL). Materials and Methods : We studied seven HL cell lines (five Nodular Sclerosis (NS) and two Mixed Cellularity (MC)) and patient peripheral blood lymphocytes (100 NS-HL and 23 MC-HL). Microsatellite instability (MSI) was assessed by PCR. Chromosomal instability and telomere dysfunction were investigated by FISH. DNA repair mechanisms were studied by transcriptomic and molecular approaches. Results : In the cell lines, we observed high MSI in L428 (4/5), KMH2, and HDLM2 (3/5), low MSI in L540, L591, and SUP-HD1, and none in L1236...
July 13, 2018: Cancers
Judith Hecker, Isabella Miller, Katharina S Götze, Mareike Verbeek
Treatment options for older patients with intermediate or high-risk acute myeloid leukemia (AML) remain unsatisfactory. Allogeneic stem cell transplantation, the treatment of choice for the majority of younger AML patients, has been hampered in elderly patients by higher treatment related mortality, comorbidities and lack of a suitable donor. With the higher availability of suitable donors as well as of reduced intensity conditioning regimens, novel low intensity treatments prior to transplantation and optimized supportive care, the number of older AML patients being successfully transplanted is steadily increasing...
July 11, 2018: Cancers
Marine Ricordel, Johann Foloppe, Delphine Antoine, Annie Findeli, Juliette Kempf, Pascale Cordier, Aude Gerbaud, Benoit Grellier, Monika Lusky, Eric Quemeneur, Philippe Erbs
Oncolytic virus (OV) therapy has emerged as a promising approach for cancer treatment with the potential to be less toxic and more efficient than classic cancer therapies. Various types of OVs in clinical development, including Vaccinia virus (VACV)-derived OVs, have shown good safety profiles, but limited therapeutic efficacy as monotherapy in some cancer models. Many different methods have been employed to improve the oncolytic potency of OVs. In this study, we used a directed evolution process, pooling different strains of VACV, including Copenhagen, Western Reserve and Wyeth strains and the attenuated modified vaccinia virus Ankara (MVA), to generate a new recombinant poxvirus with increased oncolytic properties...
July 10, 2018: Cancers
Elizabeth I Harper, Emma F Sheedy, M Sharon Stack
Age is one of the biggest risk factors for ovarian cancer. Older women have higher rates of diagnosis and death associated with the disease. In mouse models, it was shown that aged mice had greater tumor burden than their younger counterparts when intraperitoneally injected with ovarian tumor cells. While very few papers have been published looking at the direct link between ovarian cancer metastasis and age, there is a wealth of information on how age affects metastatic microenvironments. Mesothelial cells, the peritoneal extracellular matrix (ECM), fibroblasts, adipocytes and immune cells all exhibit distinct changes with age...
July 10, 2018: Cancers
John M Lamar, Vijeyaluxmy Motilal Nehru, Guy Weinberg
Epithelioid hemangioendothelioma (EHE) is a rare soft-tissue sarcoma involving cells with histologic markers that suggest an endothelial origin. Around 90% of EHEs are caused by the fusion of Transcriptional Co-activator with a PDZ-motif (TAZ) with Calmodulin Binding Transcription Activator 1 (CAMTA1), a central nervous system-specific transcription activator. The 10% of EHEs that lack the TAZ⁻CAMTA1 fusion instead have a fusion of Yes-associated Protein (YAP) and Transcription Factor E3 (TFE3) genes (YAP-TFE3)...
July 10, 2018: Cancers
Javadi Monisha, Nand Kishor Roy, Ganesan Padmavathi, Kishore Banik, Devivasha Bordoloi, Amrita Devi Khwairakpam, Frank Arfuso, Arunachalam Chinnathambi, Tahani Awad Alahmadi, Sulaiman Ali Alharbi, Gautam Sethi, Alan Prem Kumar, Ajaikumar B Kunnumakkara
Oral cancer is a major public health burden worldwide. The lack of biomarkers for early diagnosis has increased the difficulty in managing this disease. Recent studies have reported that neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, is upregulated in various tumors. In our study, we found that NGAL was significantly downregulated in primary malignant and metastatic tissues of oral cancer in comparison to normal tissues. The downregulation of NGAL was strongly correlated with both degree of differentiation and stage (I⁻IV); it can also serve as a prognostic biomarker for oral cancer...
July 10, 2018: Cancers
Yan Xu
As one of the important cancer hallmarks, metabolism reprogramming, including lipid metabolism alterations, occurs in tumor cells and the tumor microenvironment (TME). It plays an important role in tumorigenesis, progression, and metastasis. Lipids, and several lysophospholipids in particular, are elevated in the blood, ascites, and/or epithelial ovarian cancer (EOC) tissues, making them not only useful biomarkers, but also potential therapeutic targets. While the roles and signaling of these lipids in tumor cells are extensively studied, there is a significant gap in our understanding of their regulations and functions in the context of the microenvironment...
July 9, 2018: Cancers
Maider Varela-Guruceaga, Sonia Tejada-Solís, Marc García-Moure, Juan Fueyo, Candelaria Gomez-Manzano, Ana Patiño-García, Marta M Alonso
In recent years, we have seen an important progress in our comprehension of the molecular basis of pediatric brain tumors (PBTs). However, they still represent the main cause of death by disease in children. Due to the poor prognosis of some types of PBTs and the long-term adverse effects associated with the traditional treatments, oncolytic viruses (OVs) have emerged as an interesting therapeutic option since they displayed safety and high tolerability in pre-clinical and clinical levels. In this review, we summarize the OVs evaluated in different types of PBTs, mostly in pre-clinical studies, and we discuss the possible future direction of research in this field...
July 9, 2018: Cancers
Kah Poh Loh, Heidi D Klepin
The incidence of acute myeloid leukemia (AML) increases with age, but the outcomes for older adults with AML are poor due to underlying tumor biology, poor tolerance to aggressive treatment, and the physiologic changes of aging. Because of the underlying heterogeneity in health status, treatment decisions are difficult in this population. A geriatric assessment (GA) refers to the use of various validated tools to assess domains that are important in older adults including physical function, cognition, comorbidities, polypharmacy, social support, and nutritional status...
July 6, 2018: Cancers
Zachary Schrank, Gagan Chhabra, Leo Lin, Tsatsral Iderzorig, Chike Osude, Nabiha Khan, Adijan Kuckovic, Sanjana Singh, Rachel J Miller, Neelu Puri
Lung cancer is treated with many conventional therapies, such as surgery, radiation, and chemotherapy. However, these therapies have multiple undesirable side effects. To bypass the side effects elicited by these conventional treatments, molecularly-targeted therapies are currently in use or under development. Current molecularly-targeted therapies effectively target specific biomarkers, which are commonly overexpressed in lung cancers and can cause increased tumorigenicity. Unfortunately, several molecularly-targeted therapies are associated with initial dramatic responses followed by acquired resistance due to spontaneous mutations or activation of signaling pathways...
July 4, 2018: Cancers
Taichiro Goto
Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonias, often progresses to restrictive respiratory disturbance and mortality, typically within 10 years. IPF frequently coexists with lung cancer, and the combination of these two disease entities is far more difficult to treat than either lung cancer or IPF alone. In particular, surgery for lung cancer with IPF in the background increases postoperative morbidity and mortality by exacerbating pre-existing IPF, i.e., acute exacerbation of IPF (AEIPF)...
July 4, 2018: Cancers
Varsha Jain, Abigail T Berman
Radiation therapy is a major treatment modality for management of non-small cell lung cancer. Radiation pneumonitis is a dose limiting toxicity of radiotherapy, affecting its therapeutic ratio. This review presents patient and treatment related factors associated with the development of radiation pneumonitis. Research focusing on reducing the incidence of radiation pneumonitis by using information about lung ventilation, imaging-based biomarkers as well as normal tissue complication models is discussed. Recent advances in our understanding of molecular mechanisms underlying lung injury has led to the development of several targeted interventions, which are also explored in this review...
July 3, 2018: Cancers
Rosa Fontana, Maria Vivo
It has been widely shown that the focal adhesion kinase (FAK) is involved in nearly every aspect of cancer, from invasion to metastasis to epithelial⁻mesenchymal transition and maintenance of cancer stem cells. FAK has been shown to interact with p14ARF (alternative reading frame)—a well-established tumor suppressor—and functions in the negative regulation of cancer through both p53-dependent and -independent pathways. Interestingly, both FAK and ARF (human and mouse counterpart) proteins, as well as p53, are involved in autophagy—a process of “self-digestion”—whose main function is the recycling of cellular components and quality control of proteins and organelles...
June 29, 2018: Cancers
Kevin Washetine, Simon Heeke, Christelle Bonnetaud, Mehdi Kara-Borni, Marius Ilié, Sandra Lassalle, Catherine Butori, Elodie Long-Mira, Charles Hugo Marquette, Charlotte Cohen, Jérôme Mouroux, Eric Selva, Virginie Tanga, Coraline Bence, Jean-Marc Félix, Loic Gazoppi, Taycir Skhiri, Emmanuelle Gormally, Pascal Boucher, Bruno Clément, Georges Dagher, Véronique Hofman, Paul Hofman
Lung cancer is the major cause of death from cancer in the world and its incidence is increasing in women. Despite the progress made in developing immunotherapies and therapies targeting genomic alterations, improvement in the survival rate of advanced stages or metastatic patients remains low. Thus, urgent development of effective therapeutic molecules is needed. The discovery of novel therapeutic targets and their validation requires high quality biological material and associated clinical data. With this aim, we established a biobank dedicated to lung cancers...
June 29, 2018: Cancers
Ikuno Uehara, Nobuyuki Tanaka
p53 has functional roles in tumor suppression as a guardian of the genome, surveillant of oncogenic cell transformation, and as recently demonstrated, a regulator of intracellular metabolism. Accumulating evidence has shown that the tumor microenvironment, accompanied by inflammation and tissue remodeling, is important for cancer proliferation, metastasis, and maintenance of cancer stem cells (CSCs) that self-renew and generate the diverse cells comprising the tumor. Furthermore, p53 has been demonstrated to inhibit inflammatory responses, and functional loss of p53 causes excessive inflammatory reactions...
June 27, 2018: Cancers
Antonio Maurizi, Nadia Rucci
Bone metastases are frequently the final fate of breast and prostate cancer patients. According to the definition of metastasis as an incurable disease, to date there are no effective treatments for tumor-associated bone metastases and this represents a real challenge for the researchers in the field. The bone is a heterogeneous environment that represents a fertile soil for tumor cells, supporting their growth. Among the different cell types present in the bone, in this review we will focus our attention on the osteoclasts, which are crucial players in the so called “vicious cycle”, a phenomenon triggered by tumor cells eventually leading to both tumor proliferation as well as bone deregulation, thus fueling the development of bone metastasis...
June 27, 2018: Cancers
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