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https://www.readbyqxmd.com/read/28098878/early-growth-response-3-inhibits-growth-of-hepatocellular-carcinoma-cells-via-upregulation-of-fas-ligand
#1
Shujuan Zhang, Chao Xia, Cong Xu, Jing Liu, Han Zhu, Ya Yang, Fei Xu, Juanfeng Zhao, Ying Chang, Qiu Zhao
Hepatocellular carcinoma (HCC) is a prevalent malignancy with aggressive biological behavior and poor prognosis. Early growth response 3 (EGR3) is a zinc finger transcription factor, and has been studied primarily in the context of neurodevelopment, autoimmunity, inflammation and angiogenesis. Accumulating evidence indicates that EGR3 is a novel suppressor gene of tumor initiation and progression in certain cancer events, but little work has been carried out in exploring the relationship between EGR3 and HCC growth...
January 18, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28096693/gastric-and-colon-metastasis-from-breast-cancer-case-report-review-of-the-literature-and-possible-underlying-mechanisms
#2
J Carlos Villa Guzmán, J Espinosa, R Cervera, M Delgado, R Patón, J M Cordero García
Gastrointestinal metastases from breast cancer are not common. We present a 58-year-old female diagnosed with lobular breast cancer some years before whose relapses were gastric and colonic mucosal. Simultaneous metastases are extremely rare. To our knowledge, no cases of initial dual affectation have been reported. The patient also showed gastritis by Helicobacter pylori. Invasive lobular breast carcinoma is the most frequent special type of breast cancer and carries some specific molecular alterations such as loss of expression of E-cadherin...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28096512/papers-of-note-in-science-translational-medicine-9-372
#3
Leslie K Ferrarelli
This week's papers describe new therapeutic avenues to kill tumor-initiating cells in breast, ovarian, and lung cancer patients; mitigate graft-versus-host disease after hematopoietic cell transplants in leukemia patients; and stimulate bone healing in diabetic patients.
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28096419/stromal-cues-regulate-the-pancreatic-cancer-epigenome-and-metabolome
#4
Mara H Sherman, Ruth T Yu, Tiffany W Tseng, Cristovao M Sousa, Sihao Liu, Morgan L Truitt, Nanhai He, Ning Ding, Christopher Liddle, Annette R Atkins, Mathias Leblanc, Eric A Collisson, John M Asara, Alec C Kimmelman, Michael Downes, Ronald M Evans
A fibroinflammatory stromal reaction cooperates with oncogenic signaling to influence pancreatic ductal adenocarcinoma (PDAC) initiation, progression, and therapeutic outcome, yet the mechanistic underpinning of this crosstalk remains poorly understood. Here we show that stromal cues elicit an adaptive response in the cancer cell including the rapid mobilization of a transcriptional network implicated in accelerated growth, along with anabolic changes of an altered metabolome. The close overlap of stroma-induced changes in vitro with those previously shown to be regulated by oncogenic Kras in vivo suggests that oncogenic Kras signaling-a hallmark and key driver of PDAC-is contingent on stromal inputs...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096337/stress-granule-associated-protein-g3bp2-regulates-breast-tumor-initiation
#5
Nisha Gupta, Mark Badeaux, Yiqian Liu, Kamila Naxerova, Dennis Sgroi, Lance L Munn, Rakesh K Jain, Igor Garkavtsev
Breast tumors contain tumorigenic cancer cells, termed "tumor-initiating cells" (TICs), which are capable of both replenishing themselves and giving rise to populations of nontumorigenic breast cancer cells (non-TICs). However, the molecular mechanisms responsible for breast tumor initiation remain poorly understood. Here we describe a chemical screening strategy to identify small molecules that enhance the effect of chemotherapeutic agents on TIC-enriched breast cancer cells. We identified proteins that interact with the lead compound C108, including the stress granule-associated protein, GTPase-activating protein (SH3 domain)-binding protein 2, G3BP2...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096247/order-matters-the-order-of-somatic-mutations-influences-cancer-evolution
#6
David G Kent, Anthony R Green
Cancers evolve as a consequence of multiple somatic lesions, with competition between subclones and sequential subclonal evolution. Some driver mutations arise either early or late in the evolution of different individual tumors, suggesting that the final malignant properties of a subclone reflect the sum of mutations acquired rather than the order in which they arose. However, very little is known about the cellular consequences of altering the order in which mutations are acquired. Recent studies of human myeloproliferative neoplasms show that the order in which individual mutations are acquired has a dramatic impact on the cell biological and molecular properties of tumor-initiating cells...
January 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28096186/translation-reprogramming-is-an-evolutionarily-conserved-driver-of-phenotypic-plasticity-and-therapeutic-resistance-in-melanoma
#7
Paola Falletta, Luis Sanchez-Del-Campo, Jagat Chauhan, Maike Effern, Amy Kenyon, Christopher J Kershaw, Robert Siddaway, Richard Lisle, Rasmus Freter, Matthew J Daniels, Xin Lu, Thomas Tüting, Mark Middleton, Francesca M Buffa, Anne E Willis, Graham Pavitt, Ze'ev A Ronai, Tatjana Sauka-Spengler, Michael Hölzel, Colin R Goding
The intratumor microenvironment generates phenotypically distinct but interconvertible malignant cell subpopulations that fuel metastatic spread and therapeutic resistance. Whether different microenvironmental cues impose invasive or therapy-resistant phenotypes via a common mechanism is unknown. In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, and drug resistance. However, how MITF is suppressed in vivo and how MITF-low cells in tumors escape senescence are poorly understood...
January 17, 2017: Genes & Development
https://www.readbyqxmd.com/read/28095874/clinicopathological-study-of-9-cases-of-prostate-cancer-involving-the-rectal-wall
#8
Tao Tang, Zhengduo Yang, Dan Zhang, Jie Qu, Guang Liu, Shiwu Zhang
BACKGROUND: Prostate cancer involving the rectal wall is rare and may lead to diagnostic pitfalls. CASE PRESENTATION: Out of 9504 patients with rectal tumors between January 2003 and January 2015, 9 patients (elderly with a mean age of 74 years) with prostate cancer involving the rectal wall were clinically misdiagnosed with rectal cancer. The lesions were located in the rectum, and included 3 circumferential rectal masses, 1 ulceration lesion, 1 crater-like mass, and 4 protruding lesions...
January 17, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28095610/uveal-schwannoma-in-a-brown-eyed-dog
#9
Todd L Marlo, Elizabeth A Giuliano, Cecil P Moore, Gillian C Shaw, Leandro B C Teixeira
An eleven-year-old, female spayed Boxer dog was diagnosed with a uveal schwannoma (formerly known as the spindle cell tumor of the blue-eyed dog or SCTBED) despite having a uniformly brown iris. The patient presented to emergency for ocular discomfort, and the right globe was subsequently enucleated due to glaucoma and submitted for histopathology. Upon histopathologic evaluation, a uveal schwannoma was diagnosed and confirmed with immunohistochemical staining. Complete metastatic evaluation 1 and 6 months after initial presentation did not reveal evidence of metastasis, and the dog remains systemically healthy...
January 17, 2017: Veterinary Ophthalmology
https://www.readbyqxmd.com/read/28093985/ketogenic-diet-and-other-dietary-intervention-strategies-in-the-treatment-of-cancer
#10
Matteo Vergati, Eriseld Krasniqi, Girolamo Del Monte, Silvia Riondino, Doriana Vallone, Fiorella Guadagni, Patrizia Ferroni, Mario Roselli
Pre-clinical and clinical studies have investigated the role of a dysregulated metabolism in the sustainability of tumor initiation and progression. One of the most familiar metabolic alterations encountered in several types of cancers is the upregulation of glycolysis, which is also maintained in conditions of normal oxygen tension (aerobic glycolysis, Warburg effect) while oxidative phosphorylation is apparently reduced. As a result, cancer cells convert most incoming glucose to lactate. Although more rapid, adenosine triphosphate (ATP) production by glycolysis is less efficient in terms of ATP generated per unit of glucose consumed than oxidative phosphorylation...
January 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28093523/cutting-edge-nanog-activates-autophagy-under-hypoxic-stress-by-binding-to-bnip3l-promoter
#11
Meriem Hasmim, Bassam Janji, Mehdi Khaled, Muhammad Zaeem Noman, Fawzia Louache, Didier Bordereaux, Abdou Abderamane, Veronique Baud, Fathia Mami-Chouaib, Salem Chouaib
Hypoxia upregulates the core pluripotency factors NANOG, SOX2, and OCT4, associated with tumor aggressiveness and resistance to conventional anticancer treatments. We have previously reported that hypoxia-induced NANOG contributed in vitro to tumor cell resistance to autologous-specific CTL and in vivo to the in situ recruitment of immune-suppressive cells. In this study, we investigated the mechanisms underlying NANOG-mediated tumor cell resistance to specific lysis under hypoxia. We demonstrated the tumor-promoting effect of hypoxia on tumor initiation into immunodeficient mice using human non-small lung carcinoma cells...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28093273/identification-of-fhit-as-a-post-transcriptional-effector-of-thymidine-kinase-1-expression
#12
Daniel L Kiss, Catherine E Waters, Iman M Ouda, Joshua C Saldivar, Jenna R Karras, Zaynab A Amin, Seham Mahrous, Teresa Druck, Ralf A Bundschuh, Daniel R Schoenberg, Kay Huebner
FHIT is a genome caretaker gene that is silenced in >50% of cancers. Loss of Fhit protein expression promotes accumulation of DNA damage, affects apoptosis and epithelial-mesenchymal transition, though molecular mechanisms underlying these alterations have not been fully elucidated. Initiation of genome instability directly follows Fhit loss and the associated reduced Thymidine Kinase 1 (TK1) protein expression. The effects on TK1 of Fhit knockdown and Fhit induction in the current study confirmed the role of Fhit in regulating TK1 expression...
January 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28092946/carcinogenesis-of-the-oral-cavity-environmental-causes-and-potential-prevention-by-black-raspberry
#13
Karam El-Bayoumy, Kun-Ming Chen, Shang-Min Zhang, Yuan-Wan Sun, Shantu Amin, Gary Stoner, Joseph B Guttenplan
Worldwide, cancers of the oral cavity and pharynx comprise the sixth most common malignancies. Histologically, more than 90% of oral cancers are squamous cell carcinoma (SCC). Epidemiologic data strongly support the role of exogenous factors such as tobacco, alcohol, and human papilloma virus infection as major causative agents. Avoidance of risk factors has only been partially successful, and survival rates have not improved despite advances in therapeutic approaches. Therefore, new or improved approaches to prevention and/or early detection are critical...
January 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28092823/ph-lactate-and-hypoxia-reciprocity-in-regulating-high-affinity-monocarboxylate-transporter-expression-in-glioblastoma
#14
James P Caruso, Brandon J Koch, Philip D Benson, Elsa Varughese, Michael D Monterey, Amy E Lee, Ajal M Dave, Sam Kiousis, Andrew E Sloan, Saroj P Mathupala
Highly malignant brain tumors harbor the aberrant propensity for aerobic glycolysis, the excessive conversion of glucose to lactic acid even in the presence of ample tissue oxygen. Lactic acid is rapidly effluxed to the tumor microenvironment via a group of plasma-membrane transporters denoted monocarboxylate transporters (MCTs) to prevent "self-poisoning." One isoform, MCT2, has the highest affinity for lactate and thus should have the ability to respond to microenvironment conditions such as hypoxia, lactate, and pH to help maintain high glycolytic flux in the tumor...
January 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28092674/a-targetable-hb-egf-cited4-axis-controls-oncogenesis-in-lung-cancer
#15
C-H Hsieh, Y-T Chou, M-H Kuo, H-P Tsai, J-L Chang, C-W Wu
Aberrant epidermal growth factor (EGF) receptor (EGFR) signaling contributes to neoplastic initiation and progression in lung. Mutated EGFR has become as an important therapeutic target in lung cancer, whereas targeted treatment is not available for wild-type EGFR or its ligands. In this study, we found that heparin-binding (HB)-EGF, a member of the EGF family, was highly expressed in a subset of lung cancer, proliferation of which was dependent on HB-EGF signaling. Silencing of HB-EGF with RNA interference inhibited cell cycle progression in lung cancer cells...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092415/the-cluster-micrornas-mir-194-and-mir-215-suppress-the-tumorigenicity-of-intestinal-tumor-organoids
#16
Toshiaki Nakaoka, Yoshimasa Saito, Yuriko Shimamoto, Toshihide Muramatsu, Masaki Kimura, Yae Kanai, Hidetsugu Saito
Tumor stem cells with self-renewal and multipotent capacity play critical roles in the initiation and progression of cancer. Recently, a new 3D culture system known as organoid culture has been developed, allowing Lgr5-positive stem cells to form organoids that resemble the properties of original tissues. Here we established organoids derived from intestinal tumors of Apc(min/+) mice and normal intestinal epithelia of C57BL/6J mice and investigated the roles of microRNAs (miRNAs) in intestinal tumor organoids...
January 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28091590/high-performance-magneto-fluorescent-nanoparticles-assembled-from-terbium-and-gadolinium-1-3-diketones
#17
Rustem Zairov, Asiya Mustafina, Nataliya Shamsutdinova, Irek Nizameev, Beatriz Moreira, Svetlana Sudakova, Sergey Podyachev, Alfia Fattakhova, Gulnara Safina, Ingemar Lundstrom, Aidar Gubaidullin, Alberto Vomiero
Polyelectrolyte-coated nanoparticles consisting of terbium and gadolinium complexes with calix[4]arene tetra-diketone ligand were first synthesized. The antenna effect of the ligand on Tb(III) green luminescence and the presence of water molecules in the coordination sphere of Gd(III) bring strong luminescent and magnetic performance to the core-shell nanoparticles. The size and the core-shell morphology of the colloids were studied using transmission electron microscopy and dynamic light scattering. The correlation between photophysical and magnetic properties of the nanoparticles and their core composition was highlighted...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089889/myc-drives-progression-of-small-cell-lung-cancer-to-a-variant-neuroendocrine-subtype-with-vulnerability-to-aurora-kinase-inhibition
#18
Gurkan Mollaoglu, Matthew R Guthrie, Stefanie Böhm, Johannes Brägelmann, Ismail Can, Paul M Ballieu, Annika Marx, Julie George, Christine Heinen, Milind D Chalishazar, Haixia Cheng, Abbie S Ireland, Kendall E Denning, Anandaroop Mukhopadhyay, Jeffery M Vahrenkamp, Kristofer C Berrett, Timothy L Mosbruger, Jun Wang, Jessica L Kohan, Mohamed E Salama, Benjamin L Witt, Martin Peifer, Roman K Thomas, Jason Gertz, Jane E Johnson, Adi F Gazdar, Robert J Wechsler-Reya, Martin L Sos, Trudy G Oliver
Loss of the tumor suppressors RB1 and TP53 and MYC amplification are frequent oncogenic events in small cell lung cancer (SCLC). We show that Myc expression cooperates with Rb1 and Trp53 loss in the mouse lung to promote aggressive, highly metastatic tumors, that are initially sensitive to chemotherapy followed by relapse, similar to human SCLC. Importantly, MYC drives a neuroendocrine-low "variant" subset of SCLC with high NEUROD1 expression corresponding to transcriptional profiles of human SCLC. Targeted drug screening reveals that SCLC with high MYC expression is vulnerable to Aurora kinase inhibition, which, combined with chemotherapy, strongly suppresses tumor progression and increases survival...
December 31, 2016: Cancer Cell
https://www.readbyqxmd.com/read/28089234/oncogenic-kras-induced-increase-in-fluid-phase-endocytosis-is-dependent-on-n-wasp-and-is-required-for-the-formation-of-pancreatic-preneoplastic-lesions
#19
Clara Lubeseder-Martellato, Katharina Alexandrow, Ana Hidalgo-Sastre, Irina Heid, Sophie Luise Boos, Thomas Briel, Roland M Schmid, Jens T Siveke
Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Using three-dimensional mouse and human acinar tissue cultures and genetically engineered mouse models, we provide evidence that (i) KRas(G12D) leads to EGFR-dependent sustained fluid-phase endocytosis (FPE) during acinar metaplasia; (ii) variations in plasma membrane tension increase FPE and lead to ADM in vitro independently of EGFR; and (iii) that RAC1 regulates ADM formation partially through actin-dependent regulation of FPE...
December 24, 2016: EBioMedicine
https://www.readbyqxmd.com/read/28088622/reactive-oxygen-species-and-cancer-paradox-to-promote-or-to-suppress
#20
REVIEW
Sehamuddin Galadari, Anees Rahman, Siraj Pallichankandy, Faisal Thayyullathil
Reactive oxygen species (ROS), a group of highly reactive ions and molecules, are increasingly being appreciated as powerful signaling molecules involved in the regulation of a variety of biological processes. Indeed, their role is continuously being delineated in a variety of pathophysiological conditions. For instance, cancer cells are shown to have increased ROS levels in comparison to their normal counterparts. This is partly due to an enhanced metabolism and mitochondrial dysfunction in cancer cells. The escalated ROS generation in cancer cells contributes to the biochemical and molecular changes necessary for the tumor initiation, promotion and progression, as well as, tumor resistance to chemotherapy...
January 11, 2017: Free Radical Biology & Medicine
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