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intratumor heterogeneity

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https://www.readbyqxmd.com/read/29148824/biobanking-of-fresh-frozen-cancer-tissue-rna-is-stable-independent-of-tissue-type-with-less-than-1-hour-of-cold-ischemia
#1
Sang Yong Song, Jonghyun Jun, Miyeon Park, Seo Kyu Park, Wonju Choi, Kyunghee Park, Kee-Taek Jang, Myoyong Lee
BACKGROUND: The effects of preanalytical variables in tissue processing and storage periods on RNA quality of tissues have been well documented in each type of cancer. However, few studies have been performed on a comparative assessment of the impacts across different cancer tissues, even though it is well known that RNase activity is highly variable in various tissue types and RNase-rich tissues have been found to yield low-quality RNA. METHODS: We investigated the impacts of cold ischemia times and long-term storage on RNA integrity in various types of cancer tissue, which had been fresh-frozen and collected at the Samsung Medical Center Biobank...
November 17, 2017: Biopreservation and Biobanking
https://www.readbyqxmd.com/read/29148538/molecular-testing-for-braf-mutations-to-inform-melanoma-treatment-decisions-a-move-toward-precision-medicine
#2
Liang Cheng, Antonio Lopez-Beltran, Francesco Massari, Gregory T MacLennan, Rodolfo Montironi
Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation. Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma. Therefore, molecular testing for BRAF mutations is a priority in determining the course of therapy. A literature search was performed using MEDLINE/PubMed and scientific congress databases using the terms 'BRAF,' 'mutation,' and 'cancer/tumor...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29145421/radiographic-prediction-of-meningioma-grade-by-semantic-and-radiomic-features
#3
Thibaud P Coroller, Wenya Linda Bi, Elizabeth Huynh, Malak Abedalthagafi, Ayal A Aizer, Noah F Greenwald, Chintan Parmar, Vivek Narayan, Winona W Wu, Samuel Miranda de Moura, Saksham Gupta, Rameen Beroukhim, Patrick Y Wen, Ossama Al-Mefty, Ian F Dunn, Sandro Santagata, Brian M Alexander, Raymond Y Huang, Hugo J W L Aerts
OBJECTIVES: The clinical management of meningioma is guided by tumor grade and biological behavior. Currently, the assessment of tumor grade follows surgical resection and histopathologic review. Reliable techniques for pre-operative determination of tumor grade may enhance clinical decision-making. METHODS: A total of 175 meningioma patients (103 low-grade and 72 high-grade) with pre-operative contrast-enhanced T1-MRI were included. Fifteen radiomic (quantitative) and 10 semantic (qualitative) features were applied to quantify the imaging phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/29144790/evaluation-of-ki-67-index-in-core-needle-biopsies-and-matched-breast-cancer-surgical-specimens
#4
Soomin Ahn, Junghye Lee, Min-Sun Cho, Sanghui Park, Sun Hee Sung
CONTEXT: - The Ki-67 index is strongly prognostic and is used as a surrogate marker to distinguish luminal A from luminal B breast cancer types. OBJECTIVE: - To investigate differences in Ki-67 index between core needle biopsy samples and matched surgical samples in breast cancer. DESIGN: - We included patients with invasive breast cancer who did not receive neoadjuvant therapy. A total of 89 pairs of core needle biopsies and surgical specimens were collected, and the Ki-67 index was assessed in hot spot areas using an image analyzer...
November 16, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29137675/human-hyaluronic-acid-synthase-1-promotes-malignant-transformation-via-epithelial-to-mesenchymal-transition-micronucleation-and-centrosome-abnormalities
#5
Nguyet Nguyen, Awanit Kumar, Simi Chacko, Rodney J Ouellette, Anirban Ghosh
BACKGROUND: Human hyaluronic acid (HA) molecules are synthesized by three membrane spanning Hyaluronic Acid Synthases (HAS1, HAS2 and HAS3). Of the three, HAS1 is found to be localized more into the cytoplasmic space where it synthesizes intracellular HA. HA is a ubiquitous glycosaminoglycan, mainly present in the extracellular matrix (ECM) and on the cell surface, but are also detected intracellularly. Accumulation of HA in cancer cells, the cancer-surrounding stroma, and ECM is generally considered an independent prognostic factors for patients...
November 14, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29134440/ki67-labeling-index-assessment-and-prognostic-role-in-gastroenteropancreatic-neuroendocrine-neoplasms
#6
REVIEW
Günter Klöppel, Stefano La Rosa
In 1983, a monoclonal antibody, Ki67, was generated, that labeled the nuclei of proliferating non-neoplastic and neoplastic cells. The name Ki67 derived from the city of Kiel (Ki) where the antibody was produced in the university department of pathology and refers to the number of the original clone (67). Systematic assessment of the proliferative activity of tumors using Ki67 started in the 1990s, when Ki67, which only worked on frozen tissue, was complemented by the antibody MIB-1 that also worked in formalin-fixed tissues...
November 13, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29130628/characterization-of-genetic-intratumor-heterogeneity-in-colorectal-cancer-and-matching-patient-derived-spheroid-cultures
#7
Sigrid Salling Árnadóttir, Maria Jeppesen, Philippe Lamy, Jesper Bertram Bramsen, Iver Nordentoft, Michael Knudsen, Søren Vang, Mogens Rørbaek Madsen, Ole Thastrup, Jacob Thastrup, Claus Lindbjerg Andersen
Patient-derived in vitro cultures of colorectal cancer (CRC) may help guide treatment strategies prior to patient treatment. However, most previous studies have been performed on a single biopsy per tumor. The purpose of this study was to analyze multiple spatially distinct biopsies from CRCs and see how well intratumor heterogeneity (ITH) was recapitulated in matching patient-derived spheroids. Three to five biopsies were collected from six CRC tumors. Each biopsy was split in two; one half was used for spheroid culturing, the other half was used for DNA and RNA purification...
November 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29129161/navigation-through-inter-and-intratumoral-heterogeneity-of-endocrine-resistance-mechanisms-in-breast-cancer-a-potential-role-for-liquid-biopsies
#8
Florian Reinhardt, André Franken, Tanja Fehm, Hans Neubauer
The majority of breast cancers are hormone receptor positive due to the expression of the estrogen and/or progesterone receptors. Endocrine therapy is a major treatment option for all disease stages of hormone receptor-positive breast cancer and improves overall survival. However, endocrine therapy is limited by de novo and acquired resistance. Several factors have been proposed for endocrine therapy failures, which include molecular alterations in the estrogen receptor pathway, altered expression of cell-cycle regulators, autophagy, and epithelial-to-mesenchymal transition as a consequence of tumor progression and selection pressure...
November 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29123197/a-microdevice-platform-recapitulating-hypoxic-tumor-microenvironments
#9
Yuta Ando, Hoang P Ta, Daniel P Yen, Sang-Sin Lee, Sneha Raola, Keyue Shen
Hypoxia plays a central role in cancer progression and resistance to therapy. We have engineered a microdevice platform to recapitulate the intratumor oxygen gradients that drive the heterogeneous hypoxic landscapes in solid tumors. Our design features a "tumor section"-like culture by incorporating a cell layer between two diffusion barriers, where an oxygen gradient is established by cellular metabolism and physical constraints. We confirmed the oxygen gradient by numerical simulation and imaging-based oxygen sensor measurement...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29120751/breast-cancer-multiple-subtypes-within-a-tumor
#10
REVIEW
Syn Kok Yeo, Jun-Lin Guan
Breast cancer is a heterogeneous disease, and stratification of tumors is paramount to achieve better clinical outcomes. While it is common to stratify and treat breast tumors as a single entity, insights from studies on intratumoral heterogeneity and cancer stem cells raise the possibility that multiple breast cancer subtypes may coexist within a tumor. A role for plasticity in driving dynamic conversions between breast cancer subtypes is proposed, and the clinical implications include a need for combinatorial therapeutic strategies that account for the discrete disease entities and their plasticity...
November 2017: Trends in Cancer
https://www.readbyqxmd.com/read/29117356/spatio-temporal-genomic-heterogeneity-phylogeny-and-metastatic-evolution-in-salivary-adenoid-cystic-carcinoma
#11
Bin Liu, Yoshitsugu Mitani, Xiayu Rao, Mark Zafereo, Jianjun Zhang, Jianhua Zhang, P Andrew Futreal, Guillermina Lozano, Adel K El-Naggar
Background: Adenoid cystic carcinoma (ACC), an uncommon and indolent salivary gland malignancy, is characterized by varied morphologic and clinical manifestations. Molecular genetic studies of ACC identified certain structural and mutational alterations that may play a driver role in tumor development. The evolution and regional consistency of these events in ACC development progression are uncertain. Methods: To investigate the spatial and temporal clonal landscape of ACC, whole-genome sequencing and variant analyses were performed on 34 regionally sampled primary tumors and their concurrent and metachronous metastatic deposits from eight patients...
October 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29112206/intratumoral-heterogeneity-and-clonal-evolution-in-blood-malignancies-and-solid-tumors
#12
Ignacio Varela, Pablo Menendez, Alejandra Sanjuan-Pla
This meeting held at the University of Barcelona in March 2017, brought together scientists and clinicians worldwide to discuss current and future clinico-biological implications of intratumoral heterogeneity (ITH) and subclonal evolution in cancer diagnosis, patient stratification, and treatment resistance in diagnosis, treatment and follow-up. There was consensus that both longitudinal and tumor multi-region studies in matched samples are needed to better understand the dynamics of ITH. The contribution of the epigenome and microenvironment to ITH and subclone evolution remains understudied...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29110683/array-comparative-genomic-hybridization-of-18-pancreatic-ductal-adenocarcinomas-and-their-autologous-metastases
#13
Valentin Rausch, Andreas Krieg, Jordi Camps, Bianca Behrens, Manfred Beier, Darawalee Wangsa, Kerstin Heselmeyer-Haddad, Stephan E Baldus, Wolfram T Knoefel, Thomas Ried, Nikolas H Stoecklein
BACKGROUND: Mortality rates of pancreatic cancer remain high, which is mainly due to advanced disease and metastasis. We hypothesized that genomic copy number alterations are enriched in metastatic cells compared to autologous primary tumors, which may inform on cancer-related pathways possibly serving as potential targets for specific therapies. We investigated 18 pancreatic ductal adenocarcinomas, including 39 lymph node and 5 distant metastases after surgical resection. Analysis was performed with array-based comparative genomic hybridization (aCGH)...
November 6, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29106517/tpd52l2-impacts-proliferation-invasiveness-and-apoptosis-of-glioblastoma-cells-via-modulation-of-wnt-%C3%AE-catenin-snail-signaling
#14
Qiang Zhou, Jun-Jie Li, Hai Wang, Hong Li, Bing-Xi Lei, Lei Chen, Wei Xiang, Ya-Wei Liu, Annie Huang, Song-Tao Qi, Yun-Tao Lu
Intratumoral heterogeneity greatly hinders efficiency of target therapy in glioblastoma. To decipher the underlying mechanisms of heterogeneity, patient-derived adult glioblastoma (GBM) cells were separately isolated from margins of T1 gadolinium enhancing tumor lesions (PNCs) and T1 gadolinium enhancing core lesions (ECs). Single clone culture was conducted in ECs and U87MG cell line to screen clones with distinct biological phenotypes. Single cell clones with diverse phenotypes were simultaneously separated from ECs and U87 cell line...
November 2, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29105198/braf-v600e-tert-promoter-mutations-and-cdkn2a-b-homozygous-deletions-are-frequent-in-epithelioid-glioblastomas-a-histological-and-molecular-analysis-focusing-on-intratumoral-heterogeneity
#15
Nozomi Nakajima, Sumihito Nobusawa, Satoshi Nakata, Mitsutoshi Nakada, Tatsuya Yamazaki, Nozomi Matsumura, Kenichi Harada, Hadzki Matsuda, Nobuaki Funata, Shoichi Nagai, Hideo Nakamura, Atsushi Sasaki, Jiro Akimoto, Junko Hirato, Hideaki Yokoo
Epithelioid glioblastoma (E-GBM) is a rare aggressive variant of IDH-wildtype glioblastoma newly recognized in the 2016 World Health Organization classification, composed predominantly of monotonous, patternless sheets of round cells with laterally positioned nuclei and plump eosinophilic cytoplasm. Approximately 50% of E-GBM harbor BRAF V600E, which is much less frequently found in other types of glioblastomas. Most E-GBM are recognized as primary/de novo lesions; however, several E-GBM with co- or pre-existing lower-grade lesions have been reported...
November 4, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29104272/evolving-therapeutic-strategies-to-exploit-chromosome-instability-in-cancer
#16
REVIEW
Laura L Thompson, Lucile M-P Jeusset, Chloe C Lepage, Kirk J McManus
Cancer is a devastating disease that claims over 8 million lives each year. Understanding the molecular etiology of the disease is critical to identify and develop new therapeutic strategies and targets. Chromosome instability (CIN) is an abnormal phenotype, characterized by progressive numerical and/or structural chromosomal changes, which is observed in virtually all cancer types. CIN generates intratumoral heterogeneity, drives cancer development, and promotes metastatic progression, and thus, it is associated with highly aggressive, drug-resistant tumors and poor patient prognosis...
November 1, 2017: Cancers
https://www.readbyqxmd.com/read/29092944/platform-for-quantitative-evaluation-of-spatial-intratumoral-heterogeneity-in-multiplexed-fluorescence-images
#17
Daniel M Spagnolo, Yousef Al-Kofahi, Peihong Zhu, Timothy R Lezon, Albert Gough, Andrew M Stern, Adrian V Lee, Fiona Ginty, Brion Sarachan, D Lansing Taylor, S Chakra Chennubhotla
We introduce THRIVE (Tumor Heterogeneity Research Interactive Visualization Environment), an open-source tool developed to assist cancer researchers in interactive hypothesis testing. The focus of this tool is to quantify spatial intratumoral heterogeneity (ITH), and the interactions between different cell phenotypes and noncellular constituents. Specifically, we foresee applications in phenotyping cells within tumor microenvironments, recognizing tumor boundaries, identifying degrees of immune infiltration and epithelial/stromal separation, and identification of heterotypic signaling networks underlying microdomains...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/29081696/implication-of-gastric-cancer-molecular-genetic-markers-in-surgical-practice
#18
REVIEW
Marina V Nemtsova, Vladimir V Strelnikov, Alexander S Tanas, Igor I Bykov, Dmitry V Zaletaev, Viktoria V Rudenko, Alexander I Glukhov, Tatiana V Kchorobrich, Yi Li, Vadim V Tarasov, George E Barreto, Gjumrakch Aliev
INTRODUCTION: We have investigated aberrant methylation of genes CDH1, RASSF1A, MLH1, N33, DAPK, expression of genes hTERT, MMP7, MMP9, BIRC5 (survivin), PTGS2, and activity of telomerase of 106 gastric tumor samples obtained intra-operatively and 53 gastric tumor samples from the same group of patients obtained endoscopically before surgery. Biopsy specimens obtained from 50 patients with chronic calculous cholecystitis were used as a control group. Together with tissue samples obtained from different sites remote to tumors, a total of 727 samples have been studied...
October 2017: Current Genomics
https://www.readbyqxmd.com/read/29079795/comprehensive-single-cell-transcriptome-analysis-reveals-heterogeneity-in-endometrioid-adenocarcinoma-tissues
#19
Shinichi Hashimoto, Yuta Tabuchi, Hideaki Yurino, Yoshihiko Hirohashi, Shungo Deshimaru, Takuya Asano, Tasuku Mariya, Kenshiro Oshima, Yuzuru Takamura, Yoshiaki Ukita, Akio Ametani, Naoto Kondo, Norikazu Monma, Tadayuki Takeda, Sadahiko Misu, Toshitugu Okayama, Kazuho Ikeo, Tsuyoshi Saito, Shuich Kaneko, Yutaka Suzuki, Masahira Hattori, Kouji Matsushima, Toshihiko Torigoe
Single cell transcriptome analysis of a cancer tissue can provide objective assessment of subtype population or the activation of each of various microenvironment component cells. In this study, we applied our newly developed technique of single cell analysis to the myometrial infiltration side (M-side) and the endometrial side (E-side) of a human endometrioid adenocarcinoma with squamous differentiation tissues. We also analyzed spherogenic cultures derived from the same tissue to identify putative regulators of stemness in vivo...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29078205/intratumor-and-intertumor-heterogeneity-in-melanoma
#20
REVIEW
Tomasz M Grzywa, Wiktor Paskal, Paweł K Włodarski
Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment...
October 24, 2017: Translational Oncology
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