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https://www.readbyqxmd.com/read/28339833/vdac1-is-a-molecular-target-in-glioblastoma-with-its-depletion-leading-to-reprogrammed-metabolism-and-reversed-oncogenic-properties
#1
Tasleem Arif, Yakov Kerlin, Itay Nakdimon, Daniel Benharroch, Avijit Paul, Daniela Dadon-Klein, Varda Shoshan-Barmatz
Background.: Glioblastoma (GBM), an aggressive brain tumor with frequent relapses and a high mortality, still awaits an effective treatment. Like many cancers, GBM cells acquire oncogenic properties, including metabolic reprogramming, vital for growth. As such, tumor metabolism is an emerging avenue for cancer therapy. One relevant target is the voltage-dependent anion channel 1 (VDAC1), a mitochondrial protein controlling cell energy and metabolic homeostasis. Methods...
February 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339479/mouse-newborn-cells-allow-highly-productive-mouse-cytomegalovirus-replication-constituting-a-novel-convenient-primary-cell-culture-system
#2
Vu Thuy Khanh Le-Trilling, Mirko Trilling
Mammalian cell culture is indispensable for most aspects of current biomedical research. Immortalized cell lines are very convenient, but transforming principles (e.g. oncogenic viruses or their oncogenes) can heavily influence the experimental outcome. Primary cells do not share this apparent disadvantage but are more laborious to generate. Certain viruses (e.g. mouse cytomegalovirus) do not replicate efficiently in most transformed cell lines. In the past, such viruses have been routinely propagated on primary mouse embryonic fibroblasts (MEF) established around day 17 (d17) of gestation...
2017: PloS One
https://www.readbyqxmd.com/read/28339425/potential-role-of-the-ovol1-ovol2-axis-and-c-myc-in-the-progression-of-cutaneous-squamous-cell-carcinoma
#3
Takamichi Ito, Gaku Tsuji, Fumitaka Ohno, Takeshi Nakahara, Hiroshi Uchi, Masutaka Furue
OVOL1 and OVOL2 are ubiquitously conserved genes encoding C2H2 zinc-finger transcription factors in mammals. They promote epithelial cell proliferation, differentiation, and mesenchymal-to-epithelial transition, coordinately mediated via the Wnt signaling pathway. We previously reported that human OVOL1 and OVOL2 were preferentially expressed in the normal epidermis and hair follicles as well as their tumors, and found that OVOL1 is upregulated in Bowen's disease and downregulated in cutaneous squamous cell carcinoma...
March 24, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28335073/clinical-characteristics-and-whole-exome-transcriptome-sequencing-of-coexisting-chronic-myeloid-leukemia-and-myelofibrosis
#4
Malathi Kandarpa, Yi-Mi Wu, Dan Robinson, Patrick William Burke, Arul M Chinnaiyan, Moshe Talpaz
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell (HSC) disorders that can be classified on the basis of genetic, clinical, phenotypic features. Genetic lesions such as JAK2 mutations and BCR-ABL translocation are often mutually exclusive in MPN patients and lead to essential thrombocythemia, polycythemia vera or myelofibrosis (ET/PV/MF) or chronic myeloid leukemia, respectively. Nevertheless, coexistence of these genetic aberrations in the same patient has been reported. Whether these aberrations occur in the same stem cell or a different cell is unclear, but an unstable genome in the HSCs seems to be the common antecedent...
March 23, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28334900/cdk12-regulates-alternative-last-exon-mrna-splicing-and-promotes-breast-cancer-cell-invasion
#5
Jerry F Tien, Alborz Mazloomian, S-W Grace Cheng, Christopher S Hughes, Christalle C T Chow, Leanna T Canapi, Arusha Oloumi, Genny Trigo-Gonzalez, Ali Bashashati, James Xu, Vicky C-D Chang, Sohrab P Shah, Samuel Aparicio, Gregg B Morin
CDK12 (cyclin-dependent kinase 12) is a regulatory kinase with evolutionarily conserved roles in modulating transcription elongation. Recent tumor genome studies of breast and ovarian cancers highlighted recurrent CDK12 mutations, which have been shown to disrupt DNA repair in cell-based assays. In breast cancers, CDK12 is also frequently co-amplified with the HER2 (ERBB2) oncogene. The mechanisms underlying functions of CDK12 in general and in cancer remain poorly defined. Based on global analysis of mRNA transcripts in normal and breast cancer cell lines with and without CDK12 amplification, we demonstrate that CDK12 primarily regulates alternative last exon (ALE) splicing, a specialized subtype of alternative mRNA splicing, that is both gene- and cell type-specific...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334873/alternative-dna-structure-formation-in-the-mutagenic-human-c-myc-promoter
#6
Imee Marie A Del Mundo, Maha Zewail-Foote, Sean M Kerwin, Karen M Vasquez
Mutation 'hotspot' regions in the genome are susceptible to genetic instability, implicating them in diseases. These hotspots are not random and often co-localize with DNA sequences potentially capable of adopting alternative DNA structures (non-B DNA, e.g. H-DNA and G4-DNA), which have been identified as endogenous sources of genomic instability. There are regions that contain overlapping sequences that may form more than one non-B DNA structure. The extent to which one structure impacts the formation/stability of another, within the sequence, is not fully understood...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334865/structure-of-human-pofut1-its-requirement-in-ligand-independent-oncogenic-notch-signaling-and-functional-effects-of-dowling-degos-mutations
#7
Brian J McMillan, Brandon Zimmerman, Emily D Egan, Michael Lofgren, Xiang Xu, Anthony Hesser, Stephen C Blacklow
Protein O-fucosyltransferase-1 (POFUT1), which transfers fucose residues to acceptor sites on serine and threonine residues of epidermal growth factor-like repeats of recipient proteins, is essential for Notch signal transduction in mammals. Here, we examine the consequences of POFUT1 loss on the oncogenic signaling associated with certain leukemia-associated mutations of human Notch1, report the structures of human POFUT1 in free and GDP-fucose bound states, and assess the effects of Dowling-Degos mutations on human POFUT1 function...
March 17, 2017: Glycobiology
https://www.readbyqxmd.com/read/28334732/high-stmn1-level-is-associated-with-chemo-resistance-and-poor-prognosis-in-gastric-cancer-patients
#8
Tuya Bai, Takehiko Yokobori, Bolag Altan, Munenori Ide, Erito Mochiki, Mitsuhiro Yanai, Akiharu Kimura, Norimichi Kogure, Toru Yanoma, Masaki Suzuki, Pinjie Bao, Kyoichi Kaira, Takayuki Asao, Ayaka Katayama, Tadashi Handa, Navchaa Gombodorj, Masahiko Nishiyama, Tetsunari Oyama, Kyoichi Ogata, Hiroyuki Kuwano
BACKGROUND: Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to investigate STMN1 as a prognostic and predictive indicator of response to paclitaxel therapy in patients with GC, including inoperable cases. METHODS: Immunohistochemical analysis of STMN1 was performed on both operable (n=95) and inoperable GC (n=61) samples...
March 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28334655/morpholine-or-methylpiperazine-and-salicylaldimine-based-heteroleptic-square-planner-platinum-ii-complexes-in%C3%A2-vitro-anticancer-study-and-growth-retardation-effect-on-e-%C3%A2-coli
#9
Faiz-Ur Rahman, Amjad Ali, Inam Ullah Khan, Hong-Quan Duong, Shang-Bo Yu, Yue-Jian Lin, Hui Wang, Zhan-Ting Li, Dan-Wei Zhang
Morpholine and methylpiperazine are among the most important structural parts of different drugs including organic chemotherapeutic agents. In the current study we incorporated these entities as co-ligand and a series of structurally related mono- and di-metallic square planner Pt(II) complexes (Pt(II)(salicylaldimine)(morpholine)Cl C1a-C3a, Pt(II)(salicylaldimine) (methylpiperazine)Cl C1b-C3b, di-metallic Pt(II)2(bis-salicylaldimine)(morpholine)2Cl2C4a and Pt(II)2(bis-salicylaldimine)(methylpiperazine)2Cl2C4b were prepared...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28334384/the-cancer-paradigms-of-mammalian-regeneration-can-mammals-regenerate-as-amphibians
#10
Rachel Sarig, Eldad Tzahor
Regeneration in mammals is restricted to distinct tissues and occurs mainly by expansion and maturation of resident stem cells. During regeneration, even subtle mutations in the proliferating cells may cause a detrimental effect by eliciting abnormal differentiation or malignant transformation. Indeed, cancer in mammals has been shown to arise through deregulation of stem cells maturation, which often leads to a differentiation block and cell transformation. In contrast, lower organisms such as amphibians retain a remarkable regenerative capacity in various organs, which occurs via de- and re-differentiation of mature cells...
March 15, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28334365/effect-of-kit-and-pdgfra-mutations-on-survival-in-patients-with-gastrointestinal-stromal-tumors-treated-with-adjuvant-imatinib-an-exploratory-analysis-of-a-randomized-clinical-trial
#11
Heikki Joensuu, Eva Wardelmann, Harri Sihto, Mikael Eriksson, Kirsten Sundby Hall, Annette Reichardt, Jörg T Hartmann, Daniel Pink, Silke Cameron, Peter Hohenberger, Salah-Eddin Al-Batran, Marcus Schlemmer, Sebastian Bauer, Bengt Nilsson, Raija Kallio, Jouni Junnila, Aki Vehtari, Peter Reichardt
Importance: Little is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor α (PDGFRA) mutations. Objective: To investigate the effect of KIT and PDGFRA mutations on recurrence-free survival (RFS) in patients with gastrointestinal stromal tumors (GISTs) treated with surgery and adjuvant imatinib. Design, Setting, and Participants: This exploratory study is based on the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28334334/p53-and-its-mutants-on-the-slippery-road-from-stemness-to-carcinogenesis
#12
Alina Molchadsky, Varda Rotter
Normal development, tissue homeostasis and regeneration following injury rely on the proper functions of wide repertoire of stem cells (SCs) persisting during embryonic period and throughout the adult life. Therefore, SCs employ robust mechanisms to preserve their genomic integrity and avoid heritage of mutations to their daughter cells. Importantly, propagation of SCs with faulty DNA as well as dedifferentiation of genomically altered somatic cells may result in derivation of cancer SCs, which are considered to be the driving force of the tumorigenic process...
March 15, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28334277/in-bone-metastasis-mir-34a-5p-absence-inversely-correlates-with-met-expression-while-met-oncogene-is-unaffected-by-mir-34a-5p-in-non-metastatic-and-metastatic-breast-carcinomas
#13
Paola Maroni, Rossella Puglisi, Gianfranco Mattia, Alessandra Carè, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
The highlight of the molecular basis and therapeutic targets of the bone-metastatic process requires the identification of biomarkers of metastasis colonization. Here, we studied miR-34a-5p expression, and Met-receptor expression and localization in bone metastases from ductal breast carcinomas, and in ductal carcinomas without history of metastasis (20 cases). miR-34a-5p was elevated in non-metastatic breast carcinoma, intermediate in the adjacent tissue and practically absent in bone metastases, opposite to pair-matched carcinoma...
March 16, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28333954/distance-in-cancer-gene-expression-from-stem-cells-predicts-patient-survival
#14
Markus Riester, Hua-Jun Wu, Ahmet Zehir, Mithat Gönen, Andre L Moreira, Robert J Downey, Franziska Michor
The degree of histologic cellular differentiation of a cancer has been associated with prognosis but is subjectively assessed. We hypothesized that information about tumor differentiation of individual cancers could be derived objectively from cancer gene expression data, and would allow creation of a cancer phylogenetic framework that would correlate with clinical, histologic and molecular characteristics of the cancers, as well as predict prognosis. Here we utilized mRNA expression data from 4,413 patient samples with 7 diverse cancer histologies to explore the utility of ordering samples by their distance in gene expression from that of stem cells...
2017: PloS One
https://www.readbyqxmd.com/read/28333549/ksr-as-a-therapeutic-target-for-ras-dependent-cancers
#15
Beth K Neilsen, Danielle E Frodyma, Robert E Lewis, Kurt W Fisher
Targeting downstream effectors required for oncogenic Ras signaling is a potential alternative or complement to the development of more direct approaches targeting Ras in the treatment of Ras-dependent cancers. Areas covered: Here we review literature pertaining to the molecular scaffold Kinase Suppressor of Ras (KSR) and its role in promoting signals critical to tumor maintenance. We summarize the phenotypes in knockout models, describe the role of KSR in cancer, and outline the structure and function of the KSR1 and KSR2 proteins...
March 23, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28333312/establishment-maintenance-and-functional-integrity-of-the-blood-testis-barrier-in-organotypic-cultures-of-fresh-and-frozen-thawed-prepubertal-mouse-testes
#16
C Rondanino, A Maouche, L Dumont, A Oblette, N Rives
STUDY QUESTION: Can the spatio-temporal formation of an intact blood-testis barrier (BTB), which is essential for the progression of spermatogenesis, be reproduced in cultures of fresh or frozen/thawed prepubertal mouse testes? SUMMARY ANSWER: Organotypic cultures allow the establishment and maintenance of major BTB components and the formation of a functional BTB in mouse testicular tissues. WHAT IS KNOWN ALREADY: In vitro maturation of prepubertal testicular tissues is a promising approach to restore fertility in adult survivors of childhood cancer...
March 17, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28333115/modeling-and-targeting-myc-genes-in-childhood-brain-tumors
#17
REVIEW
Sonja Hutter, Sara Bolin, Holger Weishaupt, Fredrik J Swartling
Brain tumors are the second most common group of childhood cancers, accounting for about 20%-25% of all pediatric tumors. Deregulated expression of the MYC family of transcription factors, particularly c-MYC and MYCN genes, has been found in many of these neoplasms, and their expression levels are often correlated with poor prognosis. Elevated c-MYC/MYCN initiates and drives tumorigenesis in many in vivo model systems of pediatric brain tumors. Therefore, inhibition of their oncogenic function is an attractive therapeutic target...
March 23, 2017: Genes
https://www.readbyqxmd.com/read/28332584/akt-targeting-as-a-strategy-to-boost-chemotherapy-efficacy-in-non-small-cell-lung-cancer-through-metabolism-suppression
#18
Marion Le Grand, Raphael Berges, Eddy Pasquier, Marie-Pierre Montero, Laurence Borge, Alice Carrier, Sophie Vasseur, Veronique Bourgarel, Duje Buric, Nicolas André, Diane Braguer, Manon Carré
Metabolic reprogramming is a hallmark of cancer development, mediated by genetic and epigenetic alterations that may be pharmacologically targeted. Among oncogenes, the kinase Akt is commonly overexpressed in tumors and favors glycolysis, providing a rationale for using Akt inhibitors. Here, we addressed the question of whether and how inhibiting Akt activity could improve therapy of non-small cell lung cancer (NSCLC) that represents more than 80% of all lung cancer cases. First, we demonstrated that Akt inhibitors interacted synergistically with Microtubule-Targeting Agents (MTAs) and specifically in cancer cell lines, including those resistant to chemotherapy agents and anti-EGFR targeted therapies...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332504/correspondence-oncogenic-myc-persistently-upregulates-the-molecular-clock-component-rev-erb%C3%AE
#19
Brian J Altman, Annie L Hsieh, Arvin M Gouw, Chi V Dang
No abstract text is available yet for this article.
March 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28332490/correspondence-reply-to-oncogenic-myc-persistently-upregulates-the-molecular-clock-component-rev-erb%C3%AE
#20
Anton Shostak, Bianca Ruppert, Axel Diernfellner, Michael Brunner
No abstract text is available yet for this article.
March 23, 2017: Nature Communications
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