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https://www.readbyqxmd.com/read/29352734/resistance-to-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer-the-role-of-cancer-stem-cells
#1
REVIEW
Marzia Del Re, Elena Arrigoni, Giuliana Restante, Antonio Passaro, Eleonora Rofi, Stefania Crucitta, Filippo De Marinis, Antonello Di Paolo, Romano Danesi
Among the potential mechanisms involved in resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), the manifestation of stem-like properties in cancer cells seems to have a crucial role. Alterations involved in the development of TKI resistance may be acquired in a very early phase of tumorigenesis, supporting the hypothesis that these aberrations may be present in cancer stem cells (CSCs). In this regard, the characterization of tumor subclones in the initial phase and the identification of the CSCs may be helpful in planning a specific treatment to target selected biomarkers, suppress tumor growth, and prevent drug resistance...
January 20, 2018: Stem Cells
https://www.readbyqxmd.com/read/29352488/understanding-intratumor-heterogeneity-by-combining-genome-analysis-and-mathematical-modeling
#2
REVIEW
Atsushi Niida, Satoshi Nagayama, Satoru Miyano, Koshi Mimori
Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy...
January 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29351065/measurement-of-binding-strength-between-prey-proteins-interacting-with-toxoplasma-gondii-sag1-and-sag2-using-isothermal-titration-calorimetry-itc
#3
Meng-Yee Lai, Yee-Ling Lau
Following the outcome from a previously performed yeast two-hybrid experiment, the binding strength between T. gondii SAG1 and SAG2 and their respective prey proteins were further confirmed in this study. The sag1, sag2 and their prey genes were amplified and cloned into a pGEMT vector. To express the recombinant proteins, the fragments were then subcloned into a pRSETA vector and transformed into E. coli BL21 (DE3) cells. The recombinant proteins were expressed optimally at 37°C and 1mM of IPTG. The 6X His-tag fusion proteins were purified, dialyzed and concentrated...
March 26, 2018: Acta Parasitologica
https://www.readbyqxmd.com/read/29347918/somatic-evolutionary-timings-of-driver-mutations
#4
Karen Gomez, Sayaka Miura, Louise A Huuki, Brianna S Spell, Jeffrey P Townsend, Sudhir Kumar
BACKGROUND: A unified analysis of DNA sequences from hundreds of tumors concluded that the driver mutations primarily occur in the earliest stages of cancer formation, with relatively few driver mutation events detected in the late-arising subclones. However, emerging evidence from the sequencing of multiple tumors and tumor regions per individual suggests that late-arising subclones with additional driver mutations are underestimated in single-sample analyses. METHODS: To test whether driver mutations generally map to early tumor development, we examined multi-regional tumor sequencing data from 101 individuals reported in 11 published studies...
January 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29344579/prognostic-significance-of-cytogenetic-heterogeneity-in-patients-with-newly-diagnosed-multiple-myeloma
#5
Maximilian Merz, Anna Jauch, Thomas Hielscher, Tilmann Bochtler, Stefan Olaf Schönland, Anja Seckinger, Dirk Hose, Uta Bertsch, Kai Neben, Marc Steffen Raab, Jens Hillengass, Hans Salwender, Igor Wolfgang Blau, Hans-Walter Lindemann, Ingo G H Schmidt-Wolf, Christof Scheid, Mathias Haenel, Katja C Weisel, Hartmut Goldschmidt
We investigated subclonal cytogenetic aberrations (CA) detected by interphase fluorescence in situ hybridization (iFISH) in patients with newly diagnosed multiple myeloma (MM) enrolled in the Haemato Oncology Foundation for Adults in the Netherlands (HOVON)-65/German-Speaking MM Group (GMMG)-HD4 phase 3 trial. Patients were either treated with 3 cycles of vincristine, Adriamycin, and dexamethasone or bortezomib, Adriamycin, and dexamethasone and then thalidomide or bortezomib maintenance after tandem autologous transplantation...
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29337243/intratumoral-morphological-heterogeneity-can-be-an-indicator-of-genetic-heterogeneity-in-colorectal-cancer
#6
Juliane Büttner, Korinna Jöhrens, Frederick Klauschen, Michael Hummel, Dido Lenze, Wolfgang Saeger, Annika Lehmann
Anti-EGFR-targeted therapy is used to treat metastatic colorectal cancers with RAS wild-type. However, resistance to targeted therapy is often observed and can be primary or acquired. One reason for primary resistance is the presence of mutations that are undetected due to genetic heterogeneity, which can be expressed by differences present in primary tumor and distant metastasis or recurrence or by an intratumoral heterogeneity (presence of different subclones in the investigated tumor sample). The aim of our study was to investigate if morphological heterogeneity can be an indicator of intratumoral heterogeneity...
January 11, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29334678/genome-evolution-analysis-of-recurrent-testicular-malignant-mesothelioma-by-whole-genome-sequencing
#7
Shigeng Zhang, Qi Zhang, Qing Sun, Jinlong Tang, Jimin Chen, Na Ji, Yichun Zheng, Francia Fang, Wanjun Lei, Pengpeng Li, Nan Zhang
BACKGROUND/AIMS: Malignant mesothelioma of the tunica vaginalis testis is a rare and lethal disease. The genomic characteristics and genetic changes of tumor cells during the progression of this disease are unknown. METHODS: we performed whole-genome sequencing of four successive tumor samples derived from surgery and a blood sample in a single patient. RESULTS: All tumors were found to have significant C-to-T and T-to-C mutations, and amplification of copy number in chromosomes 1 and 12 were notified in all tumor samples...
January 15, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29328552/changes-in-chromosome-counts-and-patterns-in-cho-cell-lines-upon-generation-of-recombinant-cell-lines-and-subcloning
#8
Sabine Vcelar, Michael Melcher, Norbert Auer, Astrid Hrdina, Anja Puklowski, Friedrich Leisch, Vaibhav Jadhav, Till Wenger, Martina Baumann, Nicole Borth
Chinese hamster ovary cells are the number one production system for therapeutic proteins. A pre-requirement for their use in industrial production of biopharmaceuticals is to be clonal, thus originating from a single cell in order to be phenotypically and genomically identical. In the present study it was evaluated whether standard procedures, such as the generation of a recombinant cell line in combination with selection for a specific and stable phenotype (expression of the recombinant product) or subcloning have any impact on karyotype stability or homogeneity in CHO cells...
January 12, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29326119/association-of-mutations-with-morphologic-dysplasia-in-de-novo-acute-myeloid-leukemia-without-2016-who-classification-defined-cytogenetic-abnormalities
#9
Olga K Weinberg, Christopher J Gibson, Traci M Blonquist, Donna Neuberg, Olga Pozdnyakova, Frank Kuo, Benjamin L Ebert, Robert P Hasserjian
Despite improvements in our understanding of the molecular basis of acute myeloid leukemia, the association between genetic mutations with morphologic dysplasia remains unclear. In this study, we evaluated and scored dysplasia in bone marrow specimens from 168 patients with de novo acute myeloid leukemia; none of these patients had 2016 WHO Classification-defined cytogenetic abnormalities. We then performed targeted sequencing of diagnostic bone marrow aspirates for recurrent mutations associated with myeloid malignancies...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29319506/bacterial-communities-from-the-arsenic-mine-in-z%C3%A5-oty-stok-sudety-mountains-poland
#10
Tomasz Cłapa, Dorota Narożna, Rafał Siuda, Andrzej Borkowski, Marek Selwet, Cezary J Mądrzak, Ewa Koźlecka
Investigations of bacterial communities and characterization of mineralogy of the environment in the Złoty Stok As-Au deposit were carried out. PXRD analysis revealed the presence of picropharmacolite as the most common secondary arsenic mineral in the mine. Total DNA was extracted from slime streams or slime biofilms samples to investigate the bacterial communities. PCR amplification of 16S rDNA was performed followed by subcloning of its products. Over 170 clones were analyzed by means of RFLP method. Eight group of clones representing different restriction patterns were identified...
September 27, 2017: Polish Journal of Microbiology
https://www.readbyqxmd.com/read/29317874/molecular-cloning-expression-and-characterization-of-plasmid-encoding-rhomboid-4-rom4-of-tachyzoite-of-toxoplasma-gondii-rh-strain
#11
Mohammad Taghi Rahimi, Shahabeddin Sarvi, Mahdi Sharif, Saeid Abediankenari, Ehsan Ahmadpour, Reza Valadan, Ahmad Daryani
Background: The objective of this study was to clone, express and characterize the gene encoding rhomboid 4 (ROM4) proteins, a vital gene in surface adhesion and host cell invasion process of tachyzoite of T. gondii in an appropriate expression vector and eukaryotic cell for production of recombinant protein. Methods: Toxoplasma RNA was isolated from tachyzoites (RH strain) and complementary DNA was synthesized. Oligonucleotide primer pair was designed based on Toxoplasma ROM4 gene sequence with XhoI and EcoRI restriction sites at 5' end of forward and reverse primers, respectively...
October 2017: Iranian Journal of Parasitology
https://www.readbyqxmd.com/read/29316330/rna-seq-highlights-high-clonal-variation-in-monoclonal-antibody-producing-cho-cells
#12
Camila A Orellana, Esteban Marcellin, Robin W Palfreyman, Trent P Munro, Peter P Gray, Lars K Nielsen
The development of next-generation sequencing technologies has opened new opportunities to better characterize complex eukaryotic cells. Chinese hamster ovary (CHO) cells play a primary role in therapeutic protein production, with currently five of the top ten blockbuster drugs produced in CHO. However, engineering superior CHO cells with improved production features has had limited success to date and cell lines are still developed through the generation and screening of large strain pools. Here, we applied RNA sequencing to contrast a high and a low monoclonal antibody producing cell line...
January 5, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29311225/keeping-tumors-out-of-the-mapk-fitness-zone
#13
David F Stern
Greatest fitness of tumor cell subclones in patients undergoing MAPK-targeting therapies requires just-right levels of MAPK pathway signaling. New therapeutic approaches induce tumor cell death by intensifying MAPK signaling induced by inhibitor withdrawal in combination with DNA damage, or prevent selection of resistant clones with a steep fitness barrier imposed by triple combination of BRAF, MEK, and ERK inhibitors. Cancer Discov; 8(1); 20-3. ©2018 AACRSee related article by Hong et al., p. 74.
January 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29305520/soluble-slamf6-receptor-induces-strong-cd8-t-cell-effector-function-and-improves-anti-melanoma-activity-in-vivo
#14
Galit Eisenberg, Roni Engelstein, Anat Geiger, Emma Hajaj, Sharon Merims, Shoshana Frankenburg, Ronny Uzana, Abraham Rutenberg, Arthur Machlenkin, Gabi Frei, Tamar Peretz, Michal Lotem
SLAMF6, a member of the SLAM (signaling lymphocyte activation molecules) family, is a homotypic-binding immune receptor expressed on NK, T, and B lymphocytes. Phosphorylation variance between T-cell subclones prompted us to explore its role in anti-melanoma immunity. Using a 203-amino acid sequence of the human SLAMF6 (seSLAMF6) ectodomain, we found that seSLAMF6 reduced activation-induced cell death and had an anti-apoptotic effect on tumor infiltrating lymphocytes. CD8+ T cells costimulated with seSLAMF6 secreted more interferon gamma and displayed augmented cytolytic activity...
January 5, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29303512/the-significance-of-intertumor-and-intratumor-heterogeneity-in-liver-cancer
#15
REVIEW
Jinping Liu, Hien Dang, Xin Wei Wang
Genomic analyses of primary liver cancer samples reveal a complex mutational landscape with vast intertumor and intratumor heterogeneity. Different primary liver tumors and subclones within each tumor display striking molecular and biological variations. Consequently, tumor molecular heterogeneity contributes to drug resistance and tumor relapse following therapy, which poses a substantial obstruction to improving outcomes of patients with liver cancer. There is an urgent need to the compositional and functional understanding of tumor heterogeneity...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29301954/deubiquitinase-otu5-affects-root-responses-to-phosphate-starvation
#16
Ivan Kulich, Zdeňka Vojtíková, Peter Sabol, Jitka Ortmannová, Vilém Neděla, Eva Tihlaříková, Viktor Žárský
Biogenesis of the plant secondary cell wall involves many important aspects, such as phenolic compound deposition and often silica incrustation. Previously, we demonstrated the importance of the exocyst subunit EXO70H4 for biogenesis of the trichome secondary cell wall, namely for deposition of the autofluorescent and callose-rich cell wall layer. Here, we reveal that EXO70H4-driven cell wall biogenesis is constitutively active in the mature trichome, but can also be activated elsewhere upon pathogen attack, giving this study a broader significance with an overlap into phytopathology...
January 4, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29300787/plant-x-tender-an-extension-of-the-assemblx-system-for-the-assembly-and-expression-of-multigene-constructs-in-plants
#17
Tjaša Lukan, Fabian Machens, Anna Coll, Špela Baebler, Katrin Messerschmidt, Kristina Gruden
Cloning multiple DNA fragments for delivery of several genes of interest into the plant genome is one of the main technological challenges in plant synthetic biology. Despite several modular assembly methods developed in recent years, the plant biotechnology community has not widely adopted them yet, probably due to the lack of appropriate vectors and software tools. Here we present Plant X-tender, an extension of the highly efficient, scar-free and sequence-independent multigene assembly strategy AssemblX, based on overlap-depended cloning methods and rare-cutting restriction enzymes...
2018: PloS One
https://www.readbyqxmd.com/read/29296952/mosaic-chromosome-20q-deletions-are-more-frequent-in-the-aging-population
#18
Mitchell J Machiela, Weiyin Zhou, Neil Caporaso, Michael Dean, Susan M Gapstur, Lynn Goldin, Nathaniel Rothman, Victoria L Stevens, Meredith Yeager, Stephen J Chanock
Deletions on the long-arm of chromosome 20, del(20q), are common karyotypic abnormalities in myeloid disorders. Bioinformatic analyses of the B-allele frequency and log R ratio values from genome-wide association data have identified individuals who are mosaic for large structural abnormalities (>2 Mb). We investigated the most common autosomal event, namely mosaic del(20q), in 46 254 nonhematologic cancer cases and 36 229 cancer-free controls. We detected 91 mosaic del(20q) in leukocytes (80%) and buccal material (20%)...
February 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296923/the-oncogenic-membrane-protein-lmp1-sequesters-traf3-in-b-cell-lymphoma-cells-to-produce-functional-traf3-deficiency
#19
Pradeep Bangalore-Prakash, Laura L Stunz, Nurbek Mambetsariev, Amy L Whillock, Bruce S Hostager, Gail A Bishop
Loss-of-function mutations in genes encoding the signaling protein tumor necrosis factor receptor-associated factor 3 (TRAF3) are commonly found in human B-cell malignancies, especially multiple myeloma and B-cell lymphoma (BCL). B-cell TRAF3 deficiency results in enhanced cell survival, elevated activation receptor signaling, and increased activity of certain transcriptional pathways regulating expression of prosurvival proteins. A recent analysis of TRAF3 protein staining of ∼300 human BCL tissue samples revealed that a higher proportion of samples expressing the oncogenic Epstein-Barr virus-encoded protein latent membrane protein 1 (LMP1) showed low/negative TRAF3 staining than predicted...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296819/impact-of-genomic-alterations-on-outcomes-in-myelofibrosis-patients-undergoing-jak1-2-inhibitor-therapy
#20
Jay Y Spiegel, Caroline McNamara, James A Kennedy, Tony Panzarella, Andrea Arruda, Tracy Stockley, Mahadeo Sukhai, Mariam Thomas, Justyna Bartoszko, Jenny Ho, Nancy Siddiq, Dawn Maze, Aaron Schimmer, Andre Schuh, Hassan Sibai, Karen Yee, Jamie Claudio, Rebecca Devlin, Mark D Minden, Suzanne Kamel-Reid, Vikas Gupta
In myelofibrosis (MF), driver mutations in JAK2, MPL, or CALR impact survival and progression to blast phase, with the greatest risk conferred by triple-negative status. Subclonal mutations, including mutations in high-molecular risk (HMR) genes, such as ASXL1, EZH2, IDH1/2, and SRSF2 have also been associated with inferior prognosis. However, data evaluating the impact of next-generation sequencing in MF patients treated with JAK1/2 inhibitors are lacking. Using a 54-gene myeloid panel, we performed targeted sequencing on 100 MF patients treated with ruxolitinib (n = 77) or momelotinib (n = 23) and correlated mutational profiles with treatment outcomes...
September 12, 2017: Blood Advances
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