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intratumor heterogeneity

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https://www.readbyqxmd.com/read/28807683/nano-sized-drug-carriers-extravasation-intratumoral-distribution-and-their-modeling
#1
Joseph W Nichols, Yu Sakurai, Hideyoshi Harashima, You Han Bae
Navigating intratumoral drug distribution has proven to be one of the most challenging aspects of drug delivery. The barriers are significant and varied; increased diffusional distances, elevated interstitial fluid pressure, regions of dense extracellular matrix and high cell density, and overall heterogeneity. Such a long list imposes significant requirements on nano-sized carriers. Unfortunately, other capabilities are eclipsed by the distribution requirements. A drug can do no good until it reaches its target...
August 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28803425/frameshift-mutations-in-repeat-sequences-of-ank3-hacd4-tcp10l-tp53bp1-mfn1-lcmt2-rnmt-trmt6-mettl8-and-mettl16-genes-in-colon-cancers
#2
Su Yeon Yeon, Yun Sol Jo, Eun Ji Choi, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee
Diminished ANK3 contributes to cell survival by inhibiting detachment-induced apoptosis. TP53BP1 that interacts with p53 and MFN1 that encodes a mitochondrial membrane protein are considered to have tumor suppressor gene (TSG) functions. HACD4 involving fatty acid synthesis and TCPL10 with transcription regulation functions are considered TSGs. Many genes involved in DNA methylations such as LCMT2, RNMT, TRMT6, METTL8 and METTL16 are often perturbed in cancer. The aim of our study was to find whether these genes were mutated in colorectal cancer (CRC)...
August 12, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28801933/maldi-imaging-guided-microproteomic-analyses-of-heterogeneous-breast-tumors-a-pilot-study
#3
Deborah Alberts, Charles Pottier, Nicolas Smargiasso, Dominique Baiwir, Gabriel Mazzucchelli, Philippe Delvenne, Mark Kriegsmann, Daniel Kazdal, Arne Warth, Edwin De Pauw, Rémi Longuespée
PURPOSE: Matrix-assisted laser desorption/ionization (MALDI) imaging is an ideal tool to study intratumor heterogeneity (ITH) and its implication in prognostic stratification of patients. However there are some drawbacks concerning protein identification. On the other hand, laser microdissection (LMD)-based microproteomics allows retrieving thousands of protein identifications from small tissue pieces. As a proof of concept, we combined these two complementary approaches to analyze heterogeneous regions in breast tumors...
August 11, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28799059/her2-intratumoral-heterogeneity-is-independently-associated-with-incomplete-response-to-anti-her2-neoadjuvant-chemotherapy-in-her2-positive-breast-carcinoma
#4
Yanjun Hou, Hiroaki Nitta, Lai Wei, Peter M Banks, Bryce Portier, Anil V Parwani, Zaibo Li
PURPOSE: Anti-HER2 neoadjuvant chemotherapy has been widely used in HER2-positive breast cancer patients; however, pathologic complete response (pCR) is achieved in only 40-50% of patients. The aim of this study was to investigate the association of HER2 intratumoral heterogeneity (ITH) with response to anti-HER2 neoadjuvant chemotherapy. METHODS: Assessment of HER2 ITH was performed on whole tissue sections of pre-treatment samples from a cohort of 64 invasive breast carcinoma cases originally considered positive for HER2 and treated with anti-HER2 neoadjuvant chemotherapy...
August 10, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28794601/retroperitoneal-extrarenal-angiomyolipoma-at-the-surgical-bed-8-years-after-a-renal-angiomyolipoma-nephrectomy-a-case-report-and-review-of-literature
#5
Anugayathri Jawahar, Joao Kazan-Tannus
Retroperitoneal extrarenal angiomyolipoma (RERAML) are rare and close mimickers of retroperitoneal liposarcoma on both imaging and histopathology. However, imaging findings including heterogeneity, hyperdensity on unenhanced computed tomography, intralesional hemorrhage, absence of calcifications, low signal intensity on T2-weighted magnetic resonance imaging, and dilated intratumoral vessels can lead to the diagnosis of RERAML. Diagnosis of RERAML can avoid unnecessary surgery since conservative medical management with continued surveillance has been proven to be effective for RERAML whereas surgical resection is the treatment for liposarcoma...
July 2017: Urology Annals
https://www.readbyqxmd.com/read/28794454/lumican-delays-melanoma-growth-in-mice-and-drives-tumor-molecular-assembly-as-well-as-response-to-matrix-targeted-tax2-therapeutic-peptide
#6
Albin Jeanne, Valérie Untereiner, Corinne Perreau, Isabelle Proult, Cyril Gobinet, Camille Boulagnon-Rombi, Christine Terryn, Laurent Martiny, Stéphane Brézillon, Stéphane Dedieu
Lumican is a small leucine-rich proteoglycan (SLRP) being known as a key regulator of collagen fibrillogenesis. However, little attention has been given so far in studying its influence on tumor-associated matrix architecture. Here, we investigate the role of host lumican on tumor matrix organization as well as on disease progression considering an immunocompetent model of melanoma implanted in Lum (-/-) vs. wild type syngeneic mice. Conjointly, lumican impact on tumor response to matrix-targeted therapy was evaluated considering a previously validated peptide, namely TAX2, that targets matricellular thrombospondin-1...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28778029/papillotubular-carcinoma-with-an-invasive-micropapillary-carcinoma-component-of-the-breast-characterized-by-a-rapid-increase-in-size-due-to-intra-tumoral-hemorrhage-a-case-report
#7
Motonobu Watanabe, Ryota Matsuoka, Yukako Ichimura, Toshiro Takagaki, Yasushi Iitsuka
INTRODUCTION: Rapidly enlarging mammary tumors, including invasive breast tumors, are clinically rare. Invasive micropapillary carcinoma (IMPC) of the breast is known to have aggressive behavior and poor clinical course compared to invasive ductal carcinoma. CASE PRESENTATION: An 87-year-old woman presented with a rapidly enlarging tumor of the right breast over the course of 3 weeks. Ultrasonography and computed tomography of the chest revealed a giant tumor located on the right chest wall, with heterogeneous parenchymal components and several cystic lesions...
2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28776571/expanded-molecular-profiling-of-myxofibrosarcoma-reveals-potentially-actionable-targets
#8
Ellen Heitzer, Sandra Sunitsch, Magdalena M Gilg, Birgit Lohberger, Beate Rinner, Karl Kashofer, Nicole Stündl, Peter Ulz, Joanna Szkandera, Andreas Leithner, Bernadette Liegl-Atzwanger
Myxofibrosarcomas are morphologically heterogeneous soft tissue sarcomas lacking a specific immunohistochemical expression profile and recurrent genetic changes. The study was designed to gain further insights into the molecular landscape of myxofibrosarcomas by targeted re-sequencing of known cancer driver hotspot mutations and the analysis of genomewide somatic copy number alterations. A well-defined group of myxofibrosarcomas, including myxofibrosarcomas G1 (n=6), myxofibrosarcomas G3 (n=7), myxofibrosarcomas with morphologically heterogeneous and independently selectable G1 and G3 areas within a tumor (n=8), and myxofibrosarcomas G3 with subsequent tumor recurrence (n=1) or metastatic disease (n=3) were evaluated...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28770275/visualization-of-her2-specific-breast-cancer-intratumoral-heterogeneity-using-64-cu-dota-trastuzumab-pet
#9
Shinsuke Sasada, Hiroaki Kurihara, Takayuki Kinoshita, Masayuki Yoshida, Natsuki Honda, Tatsunori Shimoi, Akihiko Shimomura, Kan Yonemori, Chikako Shimizu, Akinobu Hamada, Yousuke Kanayama, Yasuyoshi Watanabe, Yasuhiro Fujiwara, Kenji Tamura
No abstract text is available yet for this article.
August 3, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28768909/addressing-metabolic-heterogeneity-in-clear-cell-renal-cell-carcinoma-with-quantitative-dixon-mri
#10
Yue Zhang, Durga Udayakumar, Ling Cai, Zeping Hu, Payal Kapur, Eun-Young Kho, Andrea Pavía-Jiménez, Michael Fulkerson, Alberto Diaz de Leon, Qing Yuan, Ivan E Dimitrov, Takeshi Yokoo, Jin Ye, Matthew A Mitsche, Hyeonwoo Kim, Jeffrey G McDonald, Yin Xi, Ananth J Madhuranthakam, Durgesh K Dwivedi, Robert E Lenkinski, Jeffrey A Cadeddu, Vitaly Margulis, James Brugarolas, Ralph J DeBerardinis, Ivan Pedrosa
BACKGROUND: Dysregulated lipid and glucose metabolism in clear cell renal cell carcinoma (ccRCC) has been implicated in disease progression, and whole tumor tissue-based assessment of these changes is challenged by the tumor heterogeneity. We studied a noninvasive quantitative MRI method that predicts metabolic alterations in the whole tumor. METHODS: We applied Dixon-based MRI for in vivo quantification of lipid accumulation (fat fraction [FF]) in targeted regions of interest of 45 primary ccRCCs and correlated these MRI measures to mass spectrometry-based lipidomics and metabolomics of anatomically colocalized tissue samples isolated from the same tumor after surgery...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28761058/heterogeneity-of-tumor-infiltrating-lymphocytes-ascribed-to-local-immune-status-rather-than-neoantigens-by-multi-omics-analysis-of-glioblastoma-multiforme
#11
Lin Feng, Haipeng Qian, Xuexin Yu, Kan Liu, Ting Xiao, Chengli Zhang, Manchao Kuang, Shujun Cheng, Xueji Li, Jinghai Wan, Kaitai Zhang
Hypothetically, intratumoral genomic heterogeneity has the potential to foster tumor-infiltrating lymphocyte (TIL) diversity; however, no study has directly tested this hypothesis by simultaneously investigating somatic mutations, TIL diversity, and immune response activity. Thus, we performed whole-exome sequencing, immune repertoire sequencing and gene expression on ten spatially separated tumor samples obtained from two tumor masses excised from a glioblastoma multiforme (GBM) patient, and we included peripheral blood as control...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28755443/application-of-liquid-biopsies-in-cancer-targeted-therapy
#12
S Sumanasuriya, M B Lambros, J S de Bono
As a growing body of evidence demonstrates intertumoral and intratumoral heterogeneity and clonal evolution, both during carcinogenesis and also throughout treatment resulting in acquired drug resistance, the utility of blood-based assays or "liquid biopsies" is becoming increasingly recognized in clinical practice and trial design. "Liquid biopsies" provide a less invasive approach to the current gold standard of interrogating tumors by tissue biopsies, which are frequently unfeasible, associated with morbidity, and cannot be performed as often...
July 29, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28754904/robust-and-accurate-digital-measurement-for-her2-amplification-in-her2-equivocal-breast-cancer-diagnosis
#13
Yuefeng Wang, Julia Y S Tsang, Yongmei Cui, Ji Cui, Ying Lin, Songli Zhao, Patrick T W Law, Sai Yin Cheung, Enders K O Ng, Gary M K Tse, Zunfu Ke
Currently, there are no recommended alternative assays for HER2 cases deemed equivocal by immunohistochemistry and fluorescent in situ hybridization. Digital PCR (ddPCR), a highly accurate method to determine DNA copy number, could be a robust alternative for clinical HER2 diagnostics. HER2 and CEP17 copy numbers were quantified using two ddPCR platforms (QX200 and RainDrop) in 102 samples of invasive breast cancers. Compared to routine assays, ddPCR gave a sensitivity and specificity of 82.8% and 97.3% respectively, with a kappa value of 0...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28754664/identification-of-a-human-airway-epithelial-cell-subpopulation-with-altered-biophysical-molecular-and-metastatic-properties
#14
Paul C Pagano, Linh M Tran, Nawal Bendris, Sean O'Byrne, Henry T Tse, Shivani Sharma, Jonathan W Hoech, Stacy J Park, Elvira L Liclican, Zhe Jing, Rui Li, Kostyantyn Krysan, Manash K Paul, Yari Fontebasso, Jill E Larsen, Shaina Hakimi, Atsuko Seki, Michael C Fishbein, James K Gimzewski, Dino Di Carlo, John D Minna, Tonya C Walser, Steven M Dubinett
Lung cancers are documented to have remarkable intratumoral genetic heterogeneity. However, little is known about the heterogeneity of biophysical properties, such as cell motility, and its relationship to early disease pathogenesis and micrometastatic dissemination. In this study, we identified and selected a subpopulation of highly migratory premalignant airway epithelial cells that were observed to migrate through microscale constrictions at up to 100-fold the rate of the unselected immortalized epithelial cell lines...
July 28, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28753844/transcriptome-wide-analysis-of-magnetic-resonance-imaging-targeted-biopsy-and-matching-surgical-specimens-from-high-risk-prostate-cancer-patients-treated-with-radical-prostatectomy-the-target-must-be-hit
#15
Jan Philipp Radtke, Mandeep Takhar, David Bonekamp, Claudia Kesch, Nicholas Erho, Marguerite du Plessis, Christine Buerki, Kaye Ong, Elai Davicioni, Markus Hohenfellner, Boris A Hadaschik
BACKGROUND: The most suspicious lesions on multiparametric magnetic resonance imaging (MRI) may be representative of final pathology. OBJECTIVE: We connect imaging with high-precision spatial annotation of biopsies and genomic cancer signatures to compare the genomic signals of the index lesion and biopsy cores of adjacent and far away locations. DESIGN, SETTING, AND PARTICIPANTS: Eleven patients diagnosed with high-risk prostate cancer on MRI/transrectal ultrasound-fusion biopsy (Bx) and treated with radical prostatectomy (RP)...
January 26, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28752247/breast-cancer-complexity-implications-of-intratumoral-heterogeneity-in-clinical-management
#16
REVIEW
Brittany Haynes, Ashapurna Sarma, Pratima Nangia-Makker, Malathy P Shekhar
Generation of intratumoral phenotypic and genetic heterogeneity has been attributed to clonal evolution and cancer stem cells that together give rise to a tumor with complex ecosystems. Each ecosystem contains various tumor cell subpopulations and stromal entities, which, depending upon their composition, can influence survival, therapy responses, and global growth of the tumor. Despite recent advances in breast cancer management, the disease has not been completely eradicated as tumors recur despite initial response to treatment...
July 27, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28752092/automated-image-analysis-of-her2-fluorescence-in-situ-hybridization-to-refine-definitions-of-genetic-heterogeneity-in-breast-cancer-tissue
#17
Gedmante Radziuviene, Allan Rasmusson, Renaldas Augulis, Daiva Lesciute-Krilaviciene, Aida Laurinaviciene, Eduard Clim, Arvydas Laurinavicius
Human epidermal growth factor receptor 2 gene- (HER2-) targeted therapy for breast cancer relies primarily on HER2 overexpression established by immunohistochemistry (IHC) with borderline cases being further tested for amplification by fluorescence in situ hybridization (FISH). Manual interpretation of HER2 FISH is based on a limited number of cells and rather complex definitions of equivocal, polysomic, and genetically heterogeneous (GH) cases. Image analysis (IA) can extract high-capacity data and potentially improve HER2 testing in borderline cases...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28751245/comparison-of-22c3-pd-l1-expression-between-surgically-resected-specimens-and-paired-tissue-microarrays-in-non-small-cell-lung-cancer
#18
Chao Li, Cheng Huang, Tony S Mok, Wu Zhuang, Haipeng Xu, Qian Miao, Xirong Fan, Weifeng Zhu, Yunjian Huang, Xiandong Lin, Kan Jiang, Dan Hu, Xiaohui Chen, Peisha Huang, Gen Lin
BACKGROUND: s: It remains unclear what extent intratumoral heterogeneity of PD-L1 expression causes discordances of PD-L1 expression between paired samples. Here, PD-L1 status was compared between whole sections from non-small cell lung cancers and the corresponding tissue microarrays (TMAs) surrogating biopsy specimens. PATIENTS AND METHODS: PD-L1 expression was evaluated by 22C3 IHC assay on 190 archival surgical specimens and matched to the TMA results. The PD-L1 expression was determined by the Tumor Proportion Score (TPS) and classified into TPS <1%, TPS 1 to 49% and TPS ≥50%...
July 24, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28750401/a-practical-approach-to-tumor-heterogeneity-in-clinical-research-and-diagnostics
#19
Giorgio Stanta, Serena Bonin
This Pathobiology issue tries to better define the complex phenomenon of intratumor heterogeneity (ITH), mostly from a practical point of view. This topic has been chosen because ITH is a central issue in tumor development and has to be investigated directly in patient tissue and immediately applied in the treatment of the presenting patient. Different types of ITH should be considered: clonal genetic and epigenetic evolution, morphological heterogeneity, and tumor sampling, heterogeneity resulting from microenvironmental autocrine and paracrine interaction, and stochastic plasticity related to different functional cell efficiencies...
July 28, 2017: Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28748969/discovering-intratumor-heterogeneity-the-next-frontier-for-pathologists
#20
J I López, G De Petris
Discovering intratumor heterogeneity is a crucial issue in modern oncologic medicine. Highly sophisticated technology such as high-throughput DNA sequencing has demonstrated the real dimension of the problem. The overwhelming majority of malignant tumors show high levels of intratumor heterogeneity when thoroughly studied. Intratumor heterogeneity develops both in temporal and spatial domains and its distribution is not deterministic making each case truly unique and unrepeatable. Pathologists are main actors in intratumor heterogeneity detection since they are the medical specialists who sample the tumors...
June 2017: Pathologica
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