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Tumour heterogeneity

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https://www.readbyqxmd.com/read/28633596/laparotomy-site-implantation-metastasis-of-carcinoma-of-the-papilla-of-vater
#1
Milan Radojkovic, Jasmina Gligorijevic, Miroslav Stojanovic, Goran Stanojevic, Ivan Ilic
Introduction Carcinomas of the papilla of Vater make up a heterogeneous group of tumours arising from different types of epithelium. Regional lymph nodes, liver and lungs are the primary sites of metastatic progression of these tumours. Case presentation We present a patient with an abdominal incision site metastasis of low-grade (mixed type) adenocarcinoma of the papilla of Vater one year after pylorus-preserving pancreaticoduodenectomy. Implantation metastasis of low-grade ampullary carcinoma in the laparotomy wound after open Whipple's procedure is unusual...
January 1, 2017: Scottish Medical Journal
https://www.readbyqxmd.com/read/28628842/matching-genomic-molecular-aberrations-with-molecular-targeted-agents-are-biliary-tract-cancers-an-ideal-playground
#2
REVIEW
Loic Verlingue, Antoine Hollebecque, Valérie Boige, Michel Ducreux, David Malka, Charles Ferté
Biliary tract cancers (BTCs) are a heterogeneous group of tumours with geographical discrepancies in terms of incidence and risk factors. However, a convergent genomic and epigenetic mutational landscape emerges from the genome-wide screens of BTCs in South East Asia, Latin America and in the Western World. Specificities are observed for some alterations and anatomical subtypes: frequent fibroblast growth factor receptor 2 (FGFR2) and isocitrate dehydrogenase 1/2 (IDH1/2) alterations are specific to intrahepatic cholangiocarcinomas (ICCs), whereas frequent ERBB2 oncogene alterations are specific to extrahepatic cholangiocarcinomas (ECCs) and gallbladder carcinomas (GBCs)...
June 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28627516/cooperative-tumour-cell-membrane-targeted-phototherapy
#3
Heegon Kim, Junsung Lee, Chanhee Oh, Ji-Ho Park
The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics...
June 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28626490/soft-tissue-sarcomas-in-the-head-and-neck-25-years-of-experience
#4
Juan Francisco Liuzzi, Maribel Da Cunha, Daniuska Salas, Saul Siso, Esteban Garriga
Sarcomas are infrequent and heterogeneous tumours. They represent 1-2% of all malignant neoplasms in adults and between 4% and 10% of head and neck cancers. METHODS: The research was retrospective, descriptive, and cross-sectional. RESULTS: A study population of 62 patients with a mean age of 44 years was obtained; the most frequent location was the soft tissues of the neck (25.3%) and the mean tumour size was 7.1 cm; the most frequent diagnosis was undifferentiated pleomorphic sarcoma (25...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28623774/discrepancy-in-braf-status-among-patients-with-metastatic-malignant-melanoma-a-meta-analysis
#5
REVIEW
Antonis Valachis, Gustav J Ullenhag
The incidence of malignant melanoma is growing rapidly. Approximately half of the cases are BRAF mutated, making treatment with kinase inhibitors a (MEK and BRAF inhibitors) preferred choice in the advanced setting. The vast majority of these patients will benefit from the treatment. It is therefore of vital importance that the BRAF analysis is reliable and reflects the true nature of the tumour. Intraindividual tumour BRAF heterogeneity may exist, and changes of BRAF status over time might occur. We reviewed the literature by searching the PubMed database and 630 potentially relevant studies were identified...
June 14, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28619976/vesical-dermoid-a-rare-bladder-tumour
#6
Ashok Kumar Sokhal, Bhupendra Pal Singh, Sunny Goel, Durgesh Kumar Saini
Dermoid cysts are benign developmental lesions consisting of tissues of more than one germ cell lineage origin. The urinary bladder is a very rare location of dermoid cysts. We report a case of an 18-year-old woman who presented with suprapubic pain, dysuria and turbid urine. Blood and serum chemistry was normal. Contrast-enhanced CT revealed a heterogeneously enhancing mass of 2.5×2 cm within the urinary bladder infiltrating fundus of urinary bladder with extraluminal extension. At cystoscopy, an irregular mass arising from the dome of the urinary bladder with a covering of hair and whitish scales was seen...
June 14, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28619759/modelling-therapy-resistance-in-brca1-2-mutant-cancers
#7
Amy Dréan, Chris T Williamson, Rachel Brough, Inger Brandsma, Malini Menon, Asha Konde, Isaac Garcia-Murillas, Helen N Pemberton, Jessica Frankum, Rumana Rafiq, Nicholas Badham, James Campbell, Aditi Gulati, Nicholas C Turner, Stephen J Pettitt, Alan Ashworth, Christopher J Lord
Although PARP inhibitors target BRCA1 or BRCA2 mutant tumour cells, drug resistance is a problem. PARP inhibitor resistance is sometimes associated with the presence of secondary or "revertant" mutations in BRCA1 or BRCA2 Whether secondary mutant tumour cells are selected for in a Darwinian fashion by treatment is unclear. Furthermore, how PARP inhibitor resistance might be therapeutically targeted is also poorly understood. Using CRISPR-mutagenesis, we generated isogenic tumour cell models with secondary BRCA1 or BRCA2 mutations...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28619028/in-vitro-downregulated-hypoxia-transcriptome-is-associated-with-poor-prognosis-in-breast-cancer
#8
Basel Abu-Jamous, Francesca M Buffa, Adrian L Harris, Asoke K Nandi
BACKGROUND: Hypoxia is a characteristic of breast tumours indicating poor prognosis. Based on the assumption that those genes which are up-regulated under hypoxia in cell-lines are expected to be predictors of poor prognosis in clinical data, many signatures of poor prognosis were identified. However, it was observed that cell line data do not always concur with clinical data, and therefore conclusions from cell line analysis should be considered with caution. As many transcriptomic cell-line datasets from hypoxia related contexts are available, integrative approaches which investigate these datasets collectively, while not ignoring clinical data, are required...
June 15, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28618431/tumour-heterogeneity-poses-a-significant-challenge-to-cancer-biomarker-research
#9
Karolina Cyll, Elin Ersvær, Ljiljana Vlatkovic, Manohar Pradhan, Wanja Kildal, Marte Avranden Kjær, Andreas Kleppe, Tarjei S Hveem, Birgitte Carlsen, Silje Gill, Sven Löffeler, Erik Skaaheim Haug, Håkon Wæhre, Prasanna Sooriakumaran, Håvard E Danielsen
BACKGROUND: The high degree of genomic diversity in cancer represents a challenge for identifying objective prognostic markers. We aimed to examine the extent of tumour heterogeneity and its effect on the evaluation of a selected prognostic marker using prostate cancer as a model. METHODS: We assessed Gleason Score (GS), DNA ploidy status and phosphatase and tensin homologue (PTEN) expression in radical prostatectomy specimens (RP) from 304 patients followed for a median of 10 years (interquartile range 6-12)...
June 15, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28618430/extreme-assay-sensitivity-in-molecular-diagnostics-further-unveils-intratumour-heterogeneity-in-metastatic-colorectal-cancer-as-well-as-artifactual-low-frequency-mutations-in-the-kras-gene
#10
Sara Mariani, Luca Bertero, Simona Osella-Abate, Cristiana Di Bello, Paola Francia di Celle, Vittoria Coppola, Anna Sapino, Paola Cassoni, Caterina Marchiò
BACKGROUND: Gene mutations in the RAS family rule out metastatic colorectal carcinomas (mCRCs) from anti-EGFR therapies. METHODS: We report a retrospective analysis by Sequenom Massarray and fast COLD-PCR followed by Sanger sequencing on 240 mCRCs. RESULTS: By Sequenom, KRAS and NRAS exons 2-3-4 were mutated in 52.9% (127/240) of tumours, while BRAF codon 600 mutations reached 5% (12/240). Fast COLD-PCR found extra mutations at KRAS exon 2 in 15/166 (9%) of samples, previously diagnosed by Sequenom as wild-type or mutated at RAS (exons 3-4) or BRAF genes...
June 15, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28618420/heterogeneity-in-gastric-cancer-from-pure-morphology-to-molecular-classifications
#11
Irene Gullo, Fátima Carneiro, Carla Oliveira, Gabriela M Almeida
Gastric cancer (GC) represents a global health concern. Despite advances in prevention, diagnosis, and therapy, GC is still the third leading cause of cancer mortality worldwide, with more than 720,000 estimated deaths in 2012. Overall survival for advanced disease is about 1 year, a dismal prognosis that is partly due to the high levels of biological heterogeneity found in GC. Indeed, GC is a highly heterogeneous disease from morphological and molecular standpoints. The numerous histological and molecular classifications currently available reflect such heterogeneity...
June 16, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28616730/contrast-enhanced-3t-mr-perfusion-of-musculoskeletal-tumours-t1-value-heterogeneity-assessment-and-evaluation-of-the-influence-of-t1-estimation-methods-on-quantitative-parameters
#12
Pedro Augusto Gondim Teixeira, Christophe Leplat, Bailiang Chen, Jacques De Verbizier, Marine Beaumont, Sammy Badr, Anne Cotten, Alain Blum
OBJECTIVE: To evaluate intra-tumour and striated muscle T1 value heterogeneity and the influence of different methods of T1 estimation on the variability of quantitative perfusion parameters. MATERIAL AND METHODS: Eighty-two patients with a histologically confirmed musculoskeletal tumour were prospectively included in this study and, with ethics committee approval, underwent contrast-enhanced MR perfusion and T1 mapping. T1 value variations in viable tumour areas and in normal-appearing striated muscle were assessed...
June 14, 2017: European Radiology
https://www.readbyqxmd.com/read/28615369/clinical-development-of-pd-1-pd-l1-immunotherapy-for-gastrointestinal-cancers-facts-and-hopes
#13
Ian Chau
Gastrointestinal (GI) cancers are among the most deadly malignancies. Whereas serial incremental survival benefits have been made with cytotoxic chemotherapy with metastatic disease, a plateau of achievement has been reached. Applying modern integrative genomic technology, distinct molecular subgroups have been identified in GI cancers. This not only highlighted the heterogeneity in tumours of each primary anatomical site, it also identified novel therapeutic targets in distinct molecular subgroups and might improve the yield of clinical success...
June 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28614831/liquid-biopsies-for-monitoring-temporal-genomic-heterogeneity-in-breast-and-colon-cancers
#14
Tiziana Venesio, Giulia Siravegna, Alberto Bardelli, Anna Sapino
Cancer is a spatial and temporal dynamic disease where differently evolving genetic clones are responsible for progression. In this landscape, the genomic heterogeneity of the primary tumours can be captured by deep-sequencing representative spatial samples. However, the recognition of genetic alterations responsible for tumour evolution remains a challenging task. Recently, the "liquid biopsy" was recognized as a powerful real-time approach for the molecular monitoring of this dynamic disease. The term "liquid biopsy" generally refers to the use of circulating (cell-free) tumour DNA (ctDNA) and circulating tumour cells (CTCs) as non-invasive biomarkers for the early diagnosis, prognosis, monitoring of clinical progression, and response to treatment in different types of tumours, including the highly genomic heterogeneous breast cancer...
June 15, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28611196/atf3-repression-of-bcl-xl-determines-apoptotic-sensitivity-tohdac-inhibitors-across-tumour-types
#15
Anderly C Chüeh, Janson Wt Tse, Michael Dickinson, Paul Ioannidis, Laura Jenkins, Lars Tögel, BeeShin Tan, Ian Luk, Mercedes Dávalos-Salas, Rebecca Nightingale, Matthew R Thompson, Bryan Rg Williams, Guillaume Lessene, Erinna F Lee, Walter D Fairlie, Amardeep S Dhillon, John M Mariadason
Purpose: Histone deacetylase inhibitors (HDACi) are epigenome-targeting small molecules approved for the treatment of cutaneous T cell lymphoma and multiple myeloma. They have also demonstrated clinical activity in AML, non-small cell lung cancer and estrogen receptor-positive breast cancer, and trials are underway assessing their activity in combination regimens including immunotherpy.  However, there is currently no clear strategy to reliably predict HDACi sensitivity. <p>In colon cancer cells, apoptotic sensitivity to HDACi is associated with transcriptional induction of multiple immediate-early (IE) genes...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28608929/high-grade-serous-carcinomas-arise-in-the-mouse-oviduct-via-defects-linked-to-the-human-disease
#16
Yali Zhai, Rong Wu, Rork Kuick, Michael S Sessine, Stephanie Schulman, Megan Green, Eric R Fearon, Kathleen R Cho
Recent studies suggest that the most common and lethal type of "ovarian" cancer, high-grade serous carcinoma (HGSC), usually arises from epithelium on the fallopian tube fimbriae, and not from the ovarian surface epithelium (OSE). We have developed Ovgp1-iCreER(T2) mice in which the Ovgp1 promoter controls expression of tamoxifen (TAM)-regulated Cre recombinase in oviductal epithelium - the murine equivalent of human fallopian tube epithelium (FTE). We employed Ovgp1-iCreER(T2) mice to show that FTE-specific inactivation of several different combinations of tumour suppressor genes recurrently mutated in human HGSCs - namely Brca1, Trp53, Rb1, and Nf1 - results in serous tubal intraepithelial carcinomas (STICs) that progress to HGSC or carcinosarcoma, and to widely metastatic disease in a subset of mice...
June 13, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28607887/odontogenic-tumours-of-jaw-a-prospective-study-on-clinico-pathological-profile-and-their-management
#17
Dwaipayan Mukherjee, Chiranjib Das, Pritam Chatterjee
Odontogenic tumours are a group of heterogeneous diseases that range from hamartomatous or non-neoplastic tissue proliferations to benign neoplasms to malignant tumours with metastatic potential. They are rare, comprising about <2-3% of all oral and maxillofacial biopsy specimens. The aim of the present study was to determine the clinico-pathological presentation of this heterogeneous group of lesions and review of literature. The present study was conducted in the ENT department of a Government Medical College and Hospital, West Bengal, India, over the period of 5 years from January 2011 to December 2015...
June 2017: Indian Journal of Otolaryngology and Head and Neck Surgery
https://www.readbyqxmd.com/read/28607403/quantification-of-within-sample-genetic-heterogeneity-from-snp-array-data
#18
Pierre Martinez, Christopher Kimberley, Nicolai J BirkBak, Andrea Marquard, Zoltan Szallasi, Trevor A Graham
Intra-tumour genetic heterogeneity (ITH) fosters drug resistance and is a critical hurdle to clinical treatment. ITH can be well-measured using multi-region sampling but this is costly and challenging to implement. There is therefore a need for tools to estimate ITH in individual samples, using standard genomic data such as SNP-arrays, that could be implemented routinely. We designed two novel scores S and R, respectively based on the Shannon diversity index and Ripley's L statistic of spatial homogeneity, to quantify ITH in single SNP-array samples...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606996/targeting-endothelin-receptor-signalling-overcomes-heterogeneity-driven-therapy-failure
#19
Michael P Smith, Emily J Rowling, Zsofia Miskolczi, Jennifer Ferguson, Loredana Spoerri, Nikolas K Haass, Olivia Sloss, Sophie McEntegart, Imanol Arozarena, Alex von Kriegsheim, Javier Rodriguez, Holly Brunton, Jivko Kmarashev, Mitchell P Levesque, Reinhard Dummer, Dennie T Frederick, Miles C Andrews, Zachary A Cooper, Keith T Flaherty, Jennifer A Wargo, Claudia Wellbrock
Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a "MITF-high" phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance "AXL-high" phenotype. > 50% of melanomas progress with enriched "AXL-high" populations, and because AXL is linked to de-differentiation and invasiveness avoiding an "AXL-high relapse" is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITF-induced expression of endothelin 1 (EDN1)...
June 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28604172/opioids-combined-with-antidepressants-or-antiepileptic-drugs-for-cancer-pain-systematic-review-and-meta-analysis
#20
Chris M Kane, Matthew R Mulvey, Sophie Wright, Cheryl Craigs, Judy M Wright, Michael I Bennett
BACKGROUND: Combining antidepressant or antiepileptic drugs with opioids has resulted in increased pain relief when used for neuropathic pain in non-cancer conditions. However, evidence to support their effectiveness in cancer pain is lacking. AIM: To determine if there is additional benefit when opioids are combined with antidepressant or antiepileptic drugs for cancer pain. DESIGN: Systematic review and meta-analysis. Randomised control trials comparing opioid analgesia in combination with antidepressant or antiepileptic drugs versus opioid monotherapy were sought...
June 1, 2017: Palliative Medicine
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