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Cancers

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https://www.readbyqxmd.com/read/29772755/temozolomide-enhances-triple-negative-breast-cancer-virotherapy-in-vitro
#1
Rodolfo Garza-Morales, Roxana Gonzalez-Ramos, Akiko Chiba, Roberto Montes de Oca-Luna, Lacey R McNally, Kelly M McMasters, Jorge G Gomez-Gutierrez
Triple-negative breast cancer (TNBC) is one of the most aggressive types of cancer, and treatment is limited to chemotherapy and radiation. Oncolytic virotherapy may be a promising approach to treat TNBC. However, oncolytic adenovirus (OAd)-based mono-therapeutic clinical trials have resulted in modest outcomes. The OAd potency could be increased by chemotherapy-induced autophagy, an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. In this study, the ability of alkylating agent temozolomide (TMZ)-induced autophagy to increase OAd replication and oncolysis in TNBC cells was evaluated...
May 17, 2018: Cancers
https://www.readbyqxmd.com/read/29762508/dicer1-syndrome-dicer1-mutations-in-rare-cancers
#2
REVIEW
Jake C Robertson, Cheryl L Jorcyk, Julia Thom Oxford
DICER1 syndrome is a rare genetic disorder that predisposes individuals to multiple cancer types. Through mutations of the gene encoding the endoribonuclease, Dicer, DICER1 syndrome disrupts the biogenesis and processing of miRNAs with subsequent disruption in control of gene expression. Since the first description of DICER1 syndrome, case reports have documented novel germline mutations of the DICER1 gene in patients with cancers as well as second site mutations that alter the function of the Dicer protein expressed...
May 15, 2018: Cancers
https://www.readbyqxmd.com/read/29757973/a-new-strategy-to-control-and-eradicate-undruggable-oncogenic-k-ras-driven-pancreatic-cancer-molecular-insights-and-core-principles-learned-from-developmental-and-evolutionary-biology
#3
REVIEW
Robert E Van Sciver, Michael P Lee, Caroline Dasom Lee, Alex C Lafever, Elizaveta Svyatova, Kevin Kanda, Amber L Colliver, Lauren L Siewertsz van Reesema, Angela M Tang-Tan, Vasilena Zheleva, Monicah N Bwayi, Minglei Bian, Rebecca L Schmidt, Lynn M Matrisian, Gloria M Petersen, Amy H Tang
Oncogenic K-RAS mutations are found in virtually all pancreatic cancers, making K-RAS one of the most targeted oncoproteins for drug development in cancer therapies. Despite intense research efforts over the past three decades, oncogenic K-RAS has remained largely "undruggable". Rather than targeting an upstream component of the RAS signaling pathway (i.e., EGFR/HER2) and/or the midstream effector kinases (i.e., RAF/MEK/ERK/PI3K/mTOR), we propose an alternative strategy to control oncogenic K-RAS signal by targeting its most downstream signaling module, Seven-In-Absentia Homolog (SIAH)...
May 14, 2018: Cancers
https://www.readbyqxmd.com/read/29747461/role-of-the-bone-microenvironment-in-the-development-of-painful-complications-of-skeletal-metastases
#4
REVIEW
Sun H Park, Matthew R Eber, D Brooke Widner, Yusuke Shiozawa
Cancer-induced bone pain (CIBP) is the most common and painful complication in patients with bone metastases. It causes a significant reduction in patient quality of life. Available analgesic treatments for CIBP, such as opioids that target the central nervous system, come with severe side effects as well as the risk of abuse and addiction. Therefore, alternative treatments for CIBP are desperately needed. Although the exact mechanisms of CIBP have not been fully elucidated, recent studies using preclinical models have demonstrated the role of the bone marrow microenvironment (e...
May 10, 2018: Cancers
https://www.readbyqxmd.com/read/29738494/toward-the-discovery-of-a-novel-class-of-yap%C3%A2-tead-interaction-inhibitors-by-virtual-screening-approach-targeting-yap%C3%A2-tead-protein%C3%A2-protein-interface
#5
Floriane Gibault, Mathilde Coevoet, Manon Sturbaut, Amaury Farce, Nicolas Renault, Frédéric Allemand, Jean-François Guichou, Anne-Sophie Drucbert, Catherine Foulon, Romain Magnez, Xavier Thuru, Matthieu Corvaisier, Guillemette Huet, Philippe Chavatte, Patricia Melnyk, Fabrice Bailly, Philippe Cotelle
Intrinsically disordered protein YAP (yes-associated protein) interacts with TEADs transcriptional factors family (transcriptional enhancer associated domain) creating three interfaces. Interface 3, between the Ω-loop of YAP and a shallow pocket of TEAD was identified as the most important TEAD zone for YAP-TEAD interaction. Using the first X-ray structure of the hYAP50⁻71 -hTEAD1209⁻426 complex (PDB 3KYS) published in 2010, a protein-protein interaction inhibitors-enriched library (175,000 chemical compounds) was screened against this hydrophobic pocket of TEAD...
May 8, 2018: Cancers
https://www.readbyqxmd.com/read/29738483/proline-rich-protein-tyrosine-kinase-2-in-inflammation-and-cancer
#6
REVIEW
Xiangdong Zhu, Yonghua Bao, Yongchen Guo, Wancai Yang
Focal adhesion kinase (FAK) and its homologous FAK-related proline-rich tyrosine kinase 2 (Pyk2) contain the same domain, exhibit high sequence homology and are defined as a distinct family of non-receptor tyrosine kinases. This group of kinases plays critical roles in cytoskeletal dynamics and cell adhesion by regulating survival and growth signaling. This review summarizes the physiological and pathological functions of Pyk2 in inflammation and cancers. In particular, overexpression of Pyk2 in cancerous tissues is correlated with poor outcomes...
May 8, 2018: Cancers
https://www.readbyqxmd.com/read/29735942/nuclear-export-inhibition-for-pancreatic-cancer-therapy
#7
REVIEW
Irfana Muqbil, Asfar S Azmi, Ramzi M Mohammad
Pancreatic cancer is a deadly disease that is resistant to most available therapeutics. Pancreatic cancer to date has no effective drugs that could enhance the survival of patients once their disease has metastasized. There is a need for the identification of novel actionable drug targets in this unusually recalcitrant cancer. Nuclear protein transport is an important mechanism that regulates the function of several tumor suppressor proteins (TSPs) in a compartmentalization-dependent manner. High expression of the nuclear exporter chromosome maintenance region 1 (CRM1) or exportin 1 (XPO1), a common feature of several cancers including pancreatic cancer, results in excessive export of critical TSPs to the incorrect cellular compartment, leading to their functional inactivation...
May 7, 2018: Cancers
https://www.readbyqxmd.com/read/29734788/yap-and-taz-in-lung-cancer-oncogenic-role-and-clinical-targeting
#8
REVIEW
Federica Lo Sardo, Sabrina Strano, Giovanni Blandino
Lung cancer is the leading cause of cancer death in the world and there is no current treatment able to efficiently treat the disease as the tumor is often diagnosed at an advanced stage. Moreover, cancer cells are often resistant or acquire resistance to the treatment. Further knowledge of the mechanisms driving lung tumorigenesis, aggressiveness, metastasization, and resistance to treatments could provide new tools for detecting the disease at an earlier stage and for a better response to therapy. In this scenario, Yes Associated Protein (YAP) and Trascriptional Coactivator with PDZ-binding motif (TAZ), the final effectors of the Hippo signaling transduction pathway, are emerging as promising therapeutic targets...
May 6, 2018: Cancers
https://www.readbyqxmd.com/read/29734786/electron-nuclear-dynamics-simulations-of-proton-cancer-therapy-reactions-water-radiolysis-and-proton-and-electron-induced-dna-damage-in-computational-prototypes
#9
Erico S Teixeira, Karthik Uppulury, Austin J Privett, Christopher Stopera, Patrick M McLaurin, Jorge A Morales
Proton cancer therapy (PCT) utilizes high-energy proton projectiles to obliterate cancerous tumors with low damage to healthy tissues and without the side effects of X-ray therapy. The healing action of the protons results from their damage on cancerous cell DNA. Despite established clinical use, the chemical mechanisms of PCT reactions at the molecular level remain elusive. This situation prevents a rational design of PCT that can maximize its therapeutic power and minimize its side effects. The incomplete characterization of PCT reactions is partially due to the health risks associated with experimental/clinical techniques applied to human subjects...
May 6, 2018: Cancers
https://www.readbyqxmd.com/read/29734785/the-guardian-of-the-genome-revisited-p53-downregulates-genes-required-for-telomere-maintenance-dna-repair-and-centromere-structure
#10
REVIEW
Eléonore Toufektchan, Franck Toledo
The p53 protein has been extensively studied for its capacity to prevent proliferation of cells with a damaged genome. Surprisingly, however, our recent analysis of mice expressing a hyperactive mutant p53 that lacks the C-terminal domain revealed that increased p53 activity may alter genome maintenance. We showed that p53 downregulates genes essential for telomere metabolism, DNA repair, and centromere structure and that a sustained p53 activity leads to phenotypic traits associated with dyskeratosis congenita and Fanconi anemia...
May 6, 2018: Cancers
https://www.readbyqxmd.com/read/29734758/the-prevalence-of-cd146-expression-in-breast-cancer-subtypes-and-its-relation-to-outcome
#11
Ingeborg E de Kruijff, Anna M Timmermans, Michael A den Bakker, Anita M A C Trapman-Jansen, Renée Foekens, Marion E Meijer-Van Gelder, Esther Oomen-de Hoop, Marcel Smid, Antoinette Hollestelle, Carolien H M van Deurzen, John A Foekens, John W M Martens, Stefan Sleijfer
CD146, involved in epithelial-to-mesenchymal transition (EMT), might affect cancer aggressiveness. We here investigated the prevalence of CD146 expression in breast cancer subtypes, its relation to prognosis, the relation between CD146 and EMT and the outcome to tamoxifen. Primary breast cancer tissues from 1342 patients were available for this retrospective study and immunohistochemically stained for CD146. For survival analyses, pure prognosis was studied by only including lymph-node negative patients who did not receive (neo)adjuvant systemic treatment ( n = 551)...
May 5, 2018: Cancers
https://www.readbyqxmd.com/read/29734756/translation-control-by-p53
#12
Justina Kasteri, Dibash Das, Xuelin Zhong, Leah Persaud, Ashleigh Francis, Hilal Muharam, Moira Sauane
The translation of mRNAs plays a critical role in the regulation of gene expression and therefore, in the regulation of cell proliferation, differentiation and apoptosis. Unrestricted initiation of translation causes malignant transformation and plays a key role in the maintenance and progression of cancers. Translation initiation is regulated by the ternary complex and the eukaryotic initiation factor 4F (eIF4F) complex. The p53 tumor suppressor protein is the most well studied mammalian transcription factor that mediates a variety of anti-proliferative processes...
May 5, 2018: Cancers
https://www.readbyqxmd.com/read/29751571/aptamers-promising-tools-for-cancer-diagnosis-and-therapy
#13
EDITORIAL
Laura Cerchia
The most common approaches to cancer treatment have been, for decades, based on surgical excision, radio- and/or chemotherapy, which, in spite of their modest survival benefits, still encounter several limitations, in part due to their lack of specificity.[...].
May 3, 2018: Cancers
https://www.readbyqxmd.com/read/29751559/insights-of-crosstalk-between-p53-protein-and-the-mkk3-mkk6-p38-mapk-signaling-pathway-in-cancer
#14
REVIEW
Lorenzo Stramucci, Angelina Pranteda, Gianluca Bossi
TP53 is universally recognized as a pivotal protein in cell-cycle fate and apoptotic induction and, unsurprisingly, it is one of the most commonly hijacked control mechanisms in cancer. Recently, the kinase MKK3 emerged as a potential therapeutic target in different types of solid tumor being linked to mutant p53 gain-of-function. In this review, we summarize the delicate relationship among p53 mutational status, MKK3/MKK6 and the downstream activated master kinase p38MAPK, dissecting a finely-tuned crosstalk, in a potentially cell-context dependent scenario that urges towards a deeper characterization of the different molecular players involved in this signaling cascade and their interactions...
May 3, 2018: Cancers
https://www.readbyqxmd.com/read/29723998/the-ebv-encoded-oncoprotein-lmp1-induces-an-epithelial-to-mesenchymal-transition-emt-via-its-ctar1-domain-through-integrin-mediated-erk-mapk-signalling
#15
Mhairi A Morris, Louise Laverick, Wenbin Wei, Alexandra M Davis, Samantha O'Neill, Liam Wood, Jack Wright, Christopher W Dawson, Lawrence S Young
The Epstein⁻Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) oncogene can induce profound effects on epithelial growth and differentiation including many of the features of the epithelial-to-mesenchymal transition (EMT). To better characterise these effects, we used the well-defined Madin Darby Canine Kidney (MDCK) epithelial cell model and found that LMP1 expression in these cells induces EMT as defined by characteristic morphological changes accompanied by loss of E-cadherin, desmosomal cadherin and tight junction protein expression...
May 1, 2018: Cancers
https://www.readbyqxmd.com/read/29723986/ebv-positive-diffuse-large-b-cell-lymphoma-and-chronic-lymphocytic-leukemia-patients-exhibit-increased-anti-dutpase-antibodies
#16
Marshall Williams, Maria Eugenia Ariza
The Epstein-Barr virus (EBV), which is a ubiquitous γ-herpesvirus, establishes a latent infection in more than 90% of the global adult population. EBV-associated malignancies have increased by 14.6% over the last 20 years, and account for approximately 1.5% of all cancers worldwide and 1.8% of all cancer deaths. However, the potential involvement/contribution of lytic proteins to the pathophysiology of EBV-associated cancers is not well understood. We have previously demonstrated that the EBV-deoxyuridine triphosphate nucleotidohydrolase (dUTPase) modulates innate and adaptive immune responses by engaging the Toll-Like Receptor 2 (TLR2), which leads to the modulation of downstream genes involved in oncogenesis, chronic inflammation, and in effector T-cell function...
May 1, 2018: Cancers
https://www.readbyqxmd.com/read/29710783/targeting-epigenetic-aberrations-in-pancreatic-cancer-a-new-path-to-improve-patient-outcomes
#17
REVIEW
Brooke D Paradise, Whitney Barham, Martín E Fernandez-Zapico
Pancreatic cancer has one of the highest mortality rates among all types of cancers. The disease is highly aggressive and typically diagnosed in late stage making it difficult to treat. Currently, the vast majority of therapeutic regimens have only modest curative effects, and most of them are in the surgical/neo-adjuvant setting. There is a great need for new and more effective treatment strategies in common clinical practice. Previously, pathogenesis of pancreatic cancer was attributed solely to genetic mutations; however, recent advancements in the field have demonstrated that aberrant activation of epigenetic pathways contributes significantly to the pathogenesis of the disease...
April 28, 2018: Cancers
https://www.readbyqxmd.com/read/29690649/responses-to-the-selective-bruton-s-tyrosine-kinase-btk-inhibitor-tirabrutinib-ono-gs-4059-in-diffuse-large-b-cell-lymphoma-cell-lines
#18
Ryohei Kozaki, Meike Vogler, Harriet S Walter, Sandrine Jayne, David Dinsdale, Reiner Siebert, Martin J S Dyer, Toshio Yoshizawa
Bruton's tyrosine kinase (BTK) is a key regulator of the B-cell receptor signaling pathway, and aberrant B-cell receptor (BCR) signaling has been implicated in the survival of malignant B-cells. However, responses of the diffuse large B-cell lymphoma (DLBCL) to inhibitors of BTK (BTKi) are infrequent, highlighting the need to identify mechanisms of resistance to BTKi as well as predictive biomarkers. We investigated the response to the selective BTKi, tirabrutinib, in a panel of 64 hematopoietic cell lines...
April 23, 2018: Cancers
https://www.readbyqxmd.com/read/29690507/hypoxia-induced-cisplatin-resistance-in-non-small-cell-lung-cancer-cells-is-mediated-by-hif-1%C3%AE-and-mutant-p53-and-can-be-overcome-by-induction-of-oxidative-stress
#19
Christophe Deben, Vanessa Deschoolmeester, Jorrit De Waele, Julie Jacobs, Jolien Van den Bossche, An Wouters, Marc Peeters, Christian Rolfo, Evelien Smits, Filip Lardon, Patrick Pauwels
The compound APR-246 (PRIMA-1MET ) is a known reactivator of (mutant) p53 and inducer of oxidative stress which can sensitize cancer cells to platinum-based chemotherapeutics. However, the effect of a hypoxic tumor environment has been largely overlooked in this interaction. This study focusses on the role of hypoxia-inducible factor-1α (HIF-1α) and the p53 tumor suppressor protein in hypoxia-induced cisplatin resistance in non-small cell lung cancer (NSCLC) cells and the potential of APR-246 to overcome this resistance...
April 21, 2018: Cancers
https://www.readbyqxmd.com/read/29690504/selective-inhibition-of-histone-deacetylation-in-melanoma-increases-targeted-gene-delivery-by-a-bacteriophage-viral-vector
#20
Samuel Campbell, Keittisak Suwan, Sajee Waramit, Eric Ofori Aboagye, Amin Hajitou
The previously developed adeno-associated virus/phage (AAVP) vector, a hybrid between M13 bacteriophage (phage) viruses that infect bacteria only and human Adeno-Associated Virus (AAV), is a promising tool in targeted gene therapy against cancer. AAVP can be administered systemically and made tissue specific through the use of ligand-directed targeting. Cancer cells and tumor-associated blood vessels overexpress the αν integrin receptors, which are involved in tumor angiogenesis and tumor invasion...
April 21, 2018: Cancers
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