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Cancer genetics

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https://www.readbyqxmd.com/read/29792808/eradication-of-established-tumors-by-chemically-self-assembled-nanoring-csan-targeted-t-cells
#1
Jacob Petersburg, Jingjing Shen, Clifford M Csizmar, Katherine A Murphy, Justin Spanier, Kari Gabrielse, Thomas S Griffith, Brian Fife, Carston R Wagner
Our laboratory has developed chemically self-assembled nanorings (CSANs) as prosthetic antigen receptors (PARs) for the non-genetic modification of T-cell surfaces. PARs have been successfully employed in vitro to activate T cells for the selective killing of leukemia cells. However, PAR efficacy has yet to be evaluated in vivo or against solid tumors. Therefore, we developed bispecific PARs that selectively target the human CD3 receptor and human Epithelial Cell Adhesion Molecule (EpCAM), which is overexpressed on multiple carcinomas and cancer stem cells...
May 24, 2018: ACS Nano
https://www.readbyqxmd.com/read/29792310/bet-inhibition-overcomes-receptor-tyrosine-kinase-mediated-cetuximab-resistance-in-hnscc
#2
Brandon Leonard, Toni M Brand, Rachel A O'Keefe, Eliot Lee, Yan Zang, Jacquelyn D Kemmer, Hua Li, Jennifer R Grandis, Neil E Bhola
Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK) including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK...
May 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29791912/differential-expression-of-micrornas-in-breast-cancers-from-four-different-ethnicities
#3
Jennifer Pollard, Phil A Burns, Tom A Hughes, Colan Ho-Yen, J Louise Jones, Geetashree Mukherjee, Ganiat O Omoniyi-Esan, Nicholas Akinwale Titloye, Valerie Speirs, Abeer M Shaaban
INTRODUCTION: Breast cancer outcomes vary across different ethnic groups. MicroRNAs (miRs) are small non-coding RNA molecules that regulate gene expression across a range of pathologies, including breast cancer. The aim of this study was to evaluate the presence and expression of miRs in breast cancer samples from different ethnic groups. MATERIALS AND METHODS: Breast cancer tissue from 4 ethnic groups, i.e., British Caucasian, British Black, Nigerian, and Indian, were identified and matched for patients' age, tumour grade/type, and 10 × 10 µm sections taken...
May 23, 2018: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29791254/a-genome-wide-mirna-screen-identifies-regulators-of-tetraploid-cell-proliferation
#4
Marc A Vittoria, Elizabeth M Shenk, Kevin P O'Rourke, Amanda F Bolgioni, Sanghee Lim, Victoria Kacprzak, Ryan J Quinton, Neil J Ganem
Tetraploid cells, which are most commonly generated by errors in cell division, are genomically unstable and have been shown to promote tumorigenesis. Recent genomic studies have estimated that ∼40% of all solid tumors have undergone a genome-doubling event during their evolution, suggesting a significant role for tetraploidy in driving the development of human cancers. To safeguard against the deleterious effects of tetraploidy, non transformed cells that fail mitosis and become tetraploid activate both the Hippo and p53 tumor suppressor pathways to restrain further proliferation...
May 23, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29791232/the-role-of-interleukin-31-polymorphisms-in-non-small-cell-lung-cancer-genetic-susceptibility-and-clinical-outcome
#5
Yongfeng Yang, Li Li, Fei Chen, Li Zhang, Hong Bu
BACKGROUND: Interleukin-31 (IL-31), a novel T helper type 2 effector cytokine, is known to have an important effect on the pathogenesis of allergic disease and tumors. However, the impact of IL-31 on human lung cancer remains unclear. METHODS: This study explored the role of IL-31 polymorphisms in lung cancer and sought to characterize how IL-31 polymorphisms correlate with lung cancer tumorigenesis and patient survival rates. Using a single-nucleotide polymorphism genotype assay, we examined the expression of two IL-31 polymorphisms (rs7977932 and rs4758680) in samples from 302 lung cancer patients and 493 control cases...
May 2018: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29791133/design-construction-and-validation-of-histone-binding-effectors-in-vitro-and-in-cells
#6
Stefan J Tekel, Cassandra M Barrett, Daniel A Vargas, Karmella A Haynes
Chromatin is a system of nuclear proteins and nucleic acids that plays a pivotal role in gene expression and cell behavior, and is therefore the subject of intense study for cell development and cancer research. Biochemistry, crystallography, and reverse genetics have elucidated the macromolecular interactions that drive chromatin regulation. One of the central mechanisms is the recognition of post translational modifications (PTMs) on histone proteins by a family of nuclear proteins known as "readers...
May 23, 2018: Biochemistry
https://www.readbyqxmd.com/read/29790687/expression-profiles-of-selected-genes-in-tumors-and-matched-surgical-margins-in-oral-cavity-cancer-do-we-have-to-pay-attention-to-the-molecular-analysis-of-the-surgical-margins
#7
Joanna K Strzelczyk, Łukasz Krakowczyk, Karolina Gołąbek, Aleksander J Owczarek
BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are associated with an interplay between genetics and the environment; they account for 3% of all diagnosed malignant tumors in men and 2% of those in women. OBJECTIVES: The aim of the study was to analyze the significance of TIMP3, SFRP1, SFRP2, CDH1, RASSF1, RORA, and DAPK1 gene expression in head and neck squamous cell carcinoma tumors, and in matching surgical margin samples. We also analyzed the association between clinical parameters and the expression of the selected genes...
April 24, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29790681/multiple-primary-lung-cancer-a-literature-review
#8
REVIEW
Anna M Romaszko, Anna Doboszyńska
Nowadays, lung cancer is a leading cause of death in both men and women worldwide. There is no clear explanation for its mortality rate. However, it is already known that genetic and environmental factors as well as oncological treatment are involved. As the incidence of lung cancer soars, the number of patients diagnosed with multiple primary lung cancers (MPLC) is also rising. While differentiating between MPLC and intrapulmonary metastasis of lung cancer is important for treatment strategy and prognosis, it is also quite complicated, particularly in the cases with similar histologies...
April 19, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29790669/genetically-determined-height-was-associated-with-lung-cancer-risk-in-east-asian-population
#9
Lu Wang, Mingtao Huang, Hui Ding, Guangfu Jin, Liang Chen, Feng Chen, Hongbing Shen
The association between adult height and risk of lung cancer has been investigated by epidemiology studies, but the results are inconsistent. Mendelian randomization (MR) analyses with individual-level data from two genome-wide association studies, including a total of 7127 lung cancer cases and 6818 controls, were carried out to explore whether adult height is causally associated with risk of lung cancer. A weighted genetic risk score (wGRS) was created based on genotypes of 101 known height-associated genetic variants...
May 23, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29790609/detection-of-hydroquinone-by-raman-spectroscopy-in-patients-with-melasma-before-and-after-treatment
#10
R Cabrera-Alonso, E Guevara, M G Ramírez-Elías, B Moncada, F J González
BACKGROUND: Melasma is an acquired, facial hyperpigmentation without a specific origin. It is regularly associated with multiple etiologic factors such as pregnancy, genetic, racial, and from estrogen administration. Among the methods to treat skin hyperpigmentation a series of skin bleaching agents have been used. At present, the most commonly used agent is known as hydroquinone. Nowadays, it is known that hydroquinone can cause cancer in animals with unknown relevance to humans. MATERIAL AND METHODS: In this work, Raman spectroscopy was used to observe the presence of hydroquinone in the skin of 18 patients who have been under treatment for melasma...
May 23, 2018: Skin Research and Technology
https://www.readbyqxmd.com/read/29790454/xpo5-genetic-polymorphisms-in-cancer-risk-and-prognosis
#11
Ana Sofia Patrão, Francisca Dias, Ana Luísa Teixeira, Joaquina Maurício, Rui Medeiros
miRNAs are small noncoding RNA molecules that have a very important role in gene expression regulation and, therefore, in cell homeostasis. SNPs in certain miRNA-related genes have been shown to influence cancer risk and prognosis. miRNA cellular processing is complex and involves multiple proteins. XPO5 is a key factor in this process as it is responsible for the nuclear export of the precursor pre-miRNA to the cytoplasm, where it will be further processed to its final miRNA conformation in order to be loaded to RNA inducing silencing complex to exert its regulatory effect...
May 23, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29790419/rictor-gene-amplification-is-correlated-with-metastasis-and-therapeutic-resistance-in-triple-negative-breast-cancer
#12
Said El Shamieh, Fatima Saleh, Salim Moussa, Joseph Kattan, Fadi Farhat
Triple-negative breast cancer (TNBC) is characterized by its aggressive behavior, metastasis and lack of targeted therapies. Herein, we discuss the clinical, histopathological and genetic profile of a woman diagnosed with TNBC. Since the patient had no durable response to chemotherapy, a genetic profiling was carried out. Next-generation sequencing analysis of 592 genes showed a missense mutation, p.E545A in PIK3CA, thus the patient was started on the mTOR inhibitor everolimus, in combination with exemestane, which controlled her pain; however, the disease progressed aggressively...
May 23, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29790359/-hereditary-breast-cancer-genetic-etiology-and-current-possibilities-of-prevention-and-surgical-treatment
#13
Alena Puchmajerová, Jannis Tornikidis, Lubor Mrňa, Markéta Havlovicová, Markéta Vlčková, Jana Chrudimská, Milan Macek, Jiří Hoch
Cancer is the second most common cause of death in our population just after cardiovascular diseases, since each third individual will become affected by it during their lifetime. Breast cancer is the most common malignancy in women. The lifetime cumulative risk of breast cancer in women under the age of 75 is around 8 % according to Czech statistics. In 70-75 % of all individuals sporadic breast carcinomas are found, with 5-10 % of all women suffer from the hereditary breast and ovarian cancer (HBOC) syndrome...
2018: Casopís Lékar̆ů C̆eských
https://www.readbyqxmd.com/read/29790357/-control-editing-of-the-genome-within-reach-or-already-in-our-hands
#14
Radim Brdička, Radoslav Omelka
Although different genome editing tools have been around for decades, the recent emergence of cheap, quick, and accessible CRISPR/Cas9 technology has led to a revolution in this field. The technique has the potential to transform medicine from curative into preventive using a gene therapy. An application of genome editing has proven to be effective for both genetic and non-genetic (e.g. infectious) diseases. However, cancer and rare diseases treatment is at the forefront of interest. Concurrently, the legal and ethical frameworks should be discussed, especially as the technology moves towards a modification of the germ cells or embryos...
2018: Casopís Lékar̆ů C̆eských
https://www.readbyqxmd.com/read/29790354/-opioids-and-new-trends-in-pain-therapy
#15
Jan Lejčko
Opioids are well known for their ability to reduce the perception of pain without a loss of consciousness. However, the influence of opioids on organism is very complex. Clinical pharmacology of currently available opioid analgesics is determined by three major factors - their opioid receptor properties, pharmacokinetic properties and genetic polymorphism in the opiate receptor and cytochrome P450 isoform. In acute severe pain are opioids very efficient. Long-term experience with opioid analgesia in patients with cancer pain has shown high favorable risk/benefit ratio...
2018: Casopís Lékar̆ů C̆eských
https://www.readbyqxmd.com/read/29790102/classification-of-malignant-and-benign-lung-nodules-using-taxonomic-diversity-index-and-phylogenetic-distance
#16
Robherson Wector de Sousa Costa, Giovanni Lucca França da Silva, Antonio Oseas de Carvalho Filho, Aristófanes Corrêa Silva, Anselmo Cardoso de Paiva, Marcelo Gattass
Lung cancer presents the highest cause of death among patients around the world, in addition of being one of the smallest survival rates after diagnosis. Therefore, this study proposes a methodology for diagnosis of lung nodules in benign and malignant tumors based on image processing and pattern recognition techniques. Mean phylogenetic distance (MPD) and taxonomic diversity index (Δ) were used as texture descriptors. Finally, the genetic algorithm in conjunction with the support vector machine were applied to select the best training model...
May 23, 2018: Medical & Biological Engineering & Computing
https://www.readbyqxmd.com/read/29789715/shared-and-independent-functions-of-apkc%C3%AE-and-par3-in-skin-tumorigenesis
#17
Susanne Vorhagen, Dominik Kleefisch, Oana-Diana Persa, Annika Graband, Alexandra Schwickert, Michael Saynisch, Michael Leitges, Carien M Niessen, Sandra Iden
The polarity proteins Par3 and aPKC are key regulators of processes altered in cancer. Par3/aPKC are thought to dynamically interact with Par6 but increasing evidence suggests that aPKC and Par3 also exert complex-independent functions. Whereas aPKCλ serves as tumor promotor, Par3 can either promote or suppress tumorigenesis. Here we asked whether and how Par3 and aPKCλ genetically interact to control two-stage skin carcinogenesis. Epidermal loss of Par3, aPKCλ, or both, strongly reduced tumor multiplicity and increased latency but inhibited invasion to similar extents, indicating that Par3 and aPKCλ function as a complex to promote tumorigenesis...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29789598/autophagy-promotes-the-survival-of-dormant-breast-cancer-cells-and-metastatic-tumour-recurrence
#18
Laura Vera-Ramirez, Suman K Vodnala, Ryan Nini, Kent W Hunter, Jeffrey E Green
Cancer recurrence after initial diagnosis and treatment is a major cause of breast cancer (BC) mortality, which results from the metastatic outbreak of dormant tumour cells. Alterations in the tumour microenvironment can trigger signalling pathways in dormant cells leading to their proliferation. However, processes involved in the initial and the long-term survival of disseminated dormant BC cells remain largely unknown. Here we show that autophagy is a critical mechanism for the survival of disseminated dormant BC cells...
May 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29789421/pericytes-in-the-premetastatic-niche
#19
REVIEW
Ana E Paiva, Luiza Lousado, Daniel A P Guerra, Patrick O Azevedo, Isadora F G Sena, Julia P Andreotti, Gabryella S P Santos, Ricardo Gonçalves, Akiva Mintz, Alexander Birbrair
The premetastatic niche formed by primary tumor-derived molecules contributes to fixation of cancer metastasis. The design of efficient therapies is limited by the current lack of knowledge about the details of cellular and molecular mechanisms involved in the premetastatic niche formation. Recently, the role of pericytes in the premetastatic niche formation and lung metastatic tropism was explored by using state-of-the-art techniques, including in vivo lineage-tracing and mice with pericyte-specific KLF4 deletion...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29789416/macrophage-derived-granulin-drives-resistance-to-immune-checkpoint-inhibition-in-metastatic-pancreatic-cancer
#20
Michael C Schmid, Valeria Quaranta, Carolyn Rainer, Sebastian Rune Nielsen, Meirion Llŷr Raymant, Muhammad S Ahmed, Dannielle D Engle, Arthur Taylor, Trish Murray, Fiona Campbell, Daniel H Palmer, David A Tuveson, Ainhoa Mielgo
The ability of disseminated cancer cells to evade the immune response is a critical step for efficient metastatic progression. Protection against an immune attack is often provided by the tumor microenvironment that suppresses and excludes cytotoxic CD8+ T cells. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease with unmet needs, yet the immunoprotective role of the metastatic tumor microenvironment in pancreatic cancer is not completely understood. In this study we find that macrophage-derived granulin contributes to cytotoxic CD8+ T cell exclusion in metastatic livers...
May 22, 2018: Cancer Research
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