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https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#1
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28429395/shrna-knock-down-of-cxcr7-inhibits-tumour-invasion-and-metastasis-in-hepatocellular-carcinoma-after-transcatheter-arterial-chemoembolization
#2
Zhong-Wei Zhao, Xiao-Xi Fan, Jing-Jing Song, Min Xu, Min-Jiang Chen, Jian-Fei Tu, Fa-Zong Wu, Deng-Ke Zhang, Lu Liu, Li Chen, Xi-Hui Ying, Jian-Song Ji
To investigate the effects of lentiviral vector-mediated shRNA suppressing CXCR7 on tumour invasion and metastasis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). HCCLM3 cell lines were cultured and assigned into the CXCR7-shRNA, negative control (NC) and blank groups. The qRT-PCR and Western blotting were applied to detect the mRNA and protein expressions of CXCR7, CXCR4 and MMP-2 in HCCLM3 cells. Cell proliferation and invasion were evaluated by MTT and Transwell assays...
April 21, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28428887/differential-intratumoral-distributions-of-cd8-and-cd163-immune-cells-as-prognostic-biomarkers-in-breast-cancer
#3
Sotirios P Fortis, Michael Sofopoulos, Nectaria N Sotiriadou, Christoforos Haritos, Christoforos K Vaxevanis, Eleftheria A Anastasopoulou, Nicole Janssen, Niki Arnogiannaki, Alexandros Ardavanis, Graham Pawelec, Sonia A Perez, Constantin N Baxevanis
BACKGROUND: Tumor immune cell infiltrates are essential in hindering cancer progression and may complement the TNM classification. CD8+ and CD163+ cells have prognostic impact in breast cancer but their spatial heterogeneity has not been extensively explored in this type of cancer. Here, their potential as prognostic biomarkers was evaluated, depending on their combined densities in the tumor center (TC) and the tumor invasive margin (IM). METHODS: CD8+ and CD163+ cells were quantified by immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples from a cohort totaling 162 patients with histologically-confirmed primary invasive non-metastatic ductal breast cancer diagnosed between 2000 and 2015...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#4
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28427434/adenovirus-mediated-cd40l-gene-transfer-increases-teffector-tregulatory-cell-ratio-and-upregulates-death-receptors-in-metastatic-melanoma-patients
#5
A Schiza, J Wenthe, S Mangsbo, E Eriksson, Anders Nilsson, T H Tötterman, A Loskog, G Ullenhag
BACKGROUND AND AIMS: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). METHODS: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide...
April 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28426929/exerting-enhanced-permeability-and-retention-effect-driven-delivery-by-ultrafine-iron-oxide-nanoparticles-with-t1-t2-switchable-magnetic-resonance-imaging-contrast
#6
Liya Wang, Jing Huang, Hongbo Chen, Hui Wu, Yaolin Xu, Yuancheng Li, Hong Yi, Yongqiang Andrew Wang, Lily Yang, Hui Mao
The poor delivery efficiency remains a major challenge in nanomaterial based tumor targeted imaging and drug delivery. This work demonstrated a strategy to improve nanoparticle delivery and intratumoral distribution using a sub-5 nm (3.5 nm core size) ultrafine iron oxide nanoparticles (uIONPs) that can easily extravasate from the tumor vasculature and readily diffuse into the tumor tissue compared to iron oxide nanoparticles (IONP) with larger sizes, followed by self-assembling in the acidic tumor interstitial space to limit their re-entering the circulation...
April 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28423548/axl-acts-as-a-tumor-suppressor-by-regulating-light-expression-in-t-lymphoma
#7
Eun-Hee Lee, Eun-Mi Kim, Kon-Young Ji, A-Reum Park, Ha-Rim Choi, Hwa-Youn Lee, Su-Man Kim, Byung Yeoup Chung, Chul-Hong Park, Hyo Jin Choi, Young-Hyeh Ko, Hyoung-Woo Bai, Hyung-Sik Kang
Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423542/dna-methylation-intratumor-heterogeneity-in-localized-lung-adenocarcinomas
#8
Kelly Quek, Jun Li, Marcos Estecio, Jiexin Zhang, Junya Fujimoto, Emily Roarty, Latasha Little, Chi-Wan Chow, Xingzhi Song, Carmen Behrens, Taiping Chen, William N William, Stephen Swisher, John Heymach, Ignacio Wistuba, Jianhua Zhang, Andrew Futreal, Jianjun Zhang
Cancers are composed of cells with distinct molecular and phenotypic features within a given tumor, a phenomenon termed intratumor heterogeneity (ITH). Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas; however, the nature of methylation ITH in lung cancers has not been well investigated. In this study, we generated methylation profiles of 48 spatially separated tumor regions from 11 localized lung adenocarcinomas and their matched normal lung tissues using Illumina Infinium Human Methylation 450K BeadChip array...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423322/intratumoral-cancer-cell-intravasation-can-occur-independent-of-invasion-into-the-adjacent-stroma
#9
Elena I Deryugina, William B Kiosses
Intravasation, active entry of cancer cells into the circulation, is often considered to be a relatively late event in tumor development occurring after stromal invasion. Here, we provide evidence that intravasation can be initiated early during tumor development and proceed in parallel to or independent of tumor invasion into surrounding stroma. By applying direct and unbiased intravasation-scoring methods to two histologically distinct human cancer types in live-animal models, we demonstrate that intravasation takes place almost exclusively within the tumor core, involves intratumoral vasculature, and does not involve vasculotropic cancer cells invading tumor-adjacent stroma and migrating along tumor-converging blood vessels...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28422753/steroid-metabolome-analysis-reveals-prevalent-glucocorticoid-excess-in-primary-aldosteronism
#10
Wiebke Arlt, Katharina Lang, Alice J Sitch, Anna S Dietz, Yara Rhayem, Irina Bancos, Annette Feuchtinger, Vasileios Chortis, Lorna C Gilligan, Philippe Ludwig, Anna Riester, Evelyn Asbach, Beverly A Hughes, Donna M O'Neil, Martin Bidlingmaier, Jeremy W Tomlinson, Zaki K Hassan-Smith, D Aled Rees, Christian Adolf, Stefanie Hahner, Marcus Quinkler, Tanja Dekkers, Jaap Deinum, Michael Biehl, Brian G Keevil, Cedric H L Shackleton, Jonathan J Deeks, Axel K Walch, Felix Beuschlein, Martin Reincke
BACKGROUND: Adrenal aldosterone excess is the most common cause of secondary hypertension and is associated with increased cardiovascular morbidity. However, adverse metabolic risk in primary aldosteronism extends beyond hypertension, with increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which cannot be easily explained by aldosterone excess. METHODS: We performed mass spectrometry-based analysis of a 24-hour urine steroid metabolome in 174 newly diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71 bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56 patients with endocrine inactive adrenal adenoma, 104 patients with mild subclinical, and 47 with clinically overt adrenal cortisol excess...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28422742/multi-omics-study-revealing-the-complexity-and-spatial-heterogeneity-of-tumor-infiltrating-lymphocytes-in-primary-liver-carcinoma
#11
Lijun Shi, Yang Zhang, Lin Feng, Liming Wang, Weiqi Rong, Fan Wu, Jianxiong Wu, Kaitai Zhang, Shujun Cheng
Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC). However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which reflects one dimension of a tumor's spatial heterogeneity, and the relationship between TIL diversity, local immune response and mutation burden remain unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene expression profiling analysis and whole-exome sequencing in parallel on five regions of each tumor and on matched adjacent normal tissues and peripheral blood from five PLC patients...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420318/advancing-clinicopathologic-diagnosis-of-high-risk-neuroblastoma-using-computerized-image-analysis-and-proteomic-profiling
#12
M Khalid Khan Niazi, Jonathan H Chung, Katherine J Heaton-Johnson, Daniel Martinez, Raquel Castellanos, Meredith S Irwin, Stephen R Master, Bruce R Pawel, Metin N Gurcan, Daniel A Weiser
A subset of patients with neuroblastoma are at extremely high risk for treatment failure, though they are not identifiable at diagnosis and therefore have the highest mortality with conventional treatment approaches. Despite tremendous understanding of clinical and biological features that correlate with prognosis, neuroblastoma at ultra-high risk for treatment failure remains a diagnostic challenge. As a first step towards improving prognostic risk stratification within the high-risk group of patients, we determined the feasibility of using computerized image analysis and proteomic profiling on single slides from diagnostic tissue specimens...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28419182/molecular-classification-of-pulmonary-sarcomatoid-carcinomas-suggests-new-therapeutic-opportunities
#13
N Pécuchet, T Vieira, N Rabbe, M Antoine, H Blons, J Cadranel, P Laurent-Puig, M Wislez
Background: Pulmonary sarcomatoid carcinoma (SC) is a rare disease with poor prognosis and with strong inter- and intratumor heterogeneity. However, molecular classification is currently focused on activating MET mutations. We sought to better characterize the molecular diversity of SC using mutational signatures that reflect different mutational processes, such as tobacco-associated adducts (signature 4), BRCA1/BRCA2 deficiency (signature 3) or APOBEC enzyme deamination (signatures 2&13)...
April 13, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28416949/circulating-tumor-dna-in-a-breast-cancer-patient-s-plasma-represents-driver-alterations-in-the-tumor-tissue
#14
Jieun Lee, Sung-Min Cho, Min Sung Kim, Sug Hyung Lee, Yeun-Jun Chung, Seung-Hyun Jung
Tumor tissues from biopsies or surgery are major sources for the next generation sequencing (NGS) study, but these procedures are invasive and have limitation to overcome intratumor heterogeneity. Recent studies have shown that driver alterations in tumor tissues can be detected by liquid biopsy which is a less invasive technique capable of both capturing the tumor heterogeneity and overcoming the difficulty in tissue sampling. However, it is still unclear whether the driver alterations in liquid biopsy can be detected by targeted NGS and how those related to the tissue biopsy...
March 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28416485/targeting-autocrine-ccl5-ccr5-axis-reprograms-immunosuppressive-myeloid-cells-and-reinvigorates-antitumor-immunity
#15
Yi Ban, Junhua Mai, Xin Li, Marisa Mitchell-Flack, Tuo Zhang, Lixing Zhang, Lotfi Chouchane, Mauro Ferrari, Haifa Shen, Xiaojing Ma
The tumor-promoting potential of CCL5 has been proposed but remains poorly understood. We demonstrate here that an autocrine CCL5-CCR5 axis is a major regulator of immunosuppressive myeloid cells (IMC) of both monocytic and granulocytic lineages. The absence of the autocrine CCL5 abrogated the generation of granulocytic myeloid-derived suppressor cells and tumor-associated macrophages. In parallel, enhanced maturation of intratumoral neutrophils and macrophages occurred in spite of tumor-derived CCL5. The refractory nature of ccl5-null myeloid precursors to tumor-derived CCL5 was attributable to their persistent lack of membrane-bound CCR5...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28413547/supratentorial-intermediate-grade-meningeal-melanocytoma-with-intratumoral-bleed-in-the-background-of-neurocutaneous-melanosis-report-of-an-unusual-case-and-review-of-literature
#16
Kuntal Das, Anup Nair, Sushila Jaiswal, Rabi Sahu, Arun Srivastava, Raj Kumar, Anant Mehrotra
Primary melanocytic tumours of the central nervous system (CNS) are rare. According to the WHO classification (2007), these tumours include diffuse leptomeningeal melanosis, melanomatosis, melanocytoma, and primary CNS melanoma. Meningeal melanocytoma, most commonly seen in the infratentorial compartment and cervical spinal cord, is a benign primary melanocytic neoplasm. Primary CNS melanoma, on the other hand, represents the malignant end of the spectrum. Intermediate grade melanocytoma is a rare histological subtype of primary meningeal tumours and is characterised by the clinicopathological features between the two extremes...
January 2017: Asian Journal of Neurosurgery
https://www.readbyqxmd.com/read/28412735/glucose-deprivation-elicits-phenotypic-plasticity-via-zeb1-mediated-expression-of-nnmt
#17
Justyna Kanska, Paul-Joseph P Aspuria, Barbie Taylor-Harding, Lindsay Spurka, Vincent Funari, Sandra Orsulic, Beth Y Karlan, W Ruprecht Wiedemeyer
Glucose is considered the primary energy source for all cells, and some cancers are addicted to glucose. Here, we investigated the functional consequences of chronic glucose deprivation in serous ovarian cancer cells. We found that cells resistant to glucose starvation (glucose-restricted cells) demonstrated increased metabolic plasticity that was dependent on NNMT (Nicotinamide N-methyltransferase) expression. We further show that ZEB1 induced NNMT, rendered cells resistant to glucose deprivation and recapitulated metabolic adaptations and mesenchymal gene expression observed in glucose-restricted cells...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411844/research-techniques-made-simple-mass-cytometry%C3%A2-analysis-tools-for-decrypting-the%C3%A2-complexity%C3%A2-of-biological-systems
#18
Tiago R Matos, Hongye Liu, Jerome Ritz
Mass cytometry by time-of-flight experiments allow analysis of over 40 functional and phenotypic cellular markers simultaneously at the single-cell level. The data dimensionality escalation accentuates limitations, inherent to manual analysis, as being subjective, labor-intensive, slow, and often incapable of showing the detailed features of each unique cell within populations. The subsequent challenge of examining, visualizing, and presenting mass cytometry data has motivated continuous development of dimensionality reduction methods...
May 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28409734/intratumoral-delivery-of-bortezomib-impact-on-survival-in-an-intracranial-glioma-tumor-model
#19
Weijun Wang, Hee-Yeon Cho, Rachel Rosenstein-Sisson, Nagore I Marín Ramos, Ryan Price, Kyle Hurth, Axel H Schönthal, Florence M Hofman, Thomas C Chen
OBJECTIVE Glioblastoma (GBM) is the most prevalent and the most aggressive of primary brain tumors. There is currently no effective treatment for this tumor. The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for GBM. The authors' goal was to demonstrate that bortezomib can be effective in the orthotopic GBM murine model if the appropriate method of drug delivery is used. In this study the Alzet mini-osmotic pump was used to bring the drug directly to the tumor in the brain, circumventing the blood-brain barrier; thus making bortezomib an effective treatment for GBM...
April 14, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28408533/brachytherapy-with-intratumoral-injections-of-radiometal-labeled-polymers-that-thermo-responsively-self-aggregate-in-tumor-tissues
#20
Kohei Sano, Yuko Kanada, Kengo Kanazaki, Ning Ding, Masahiro Ono, Hideo Saji
Brachytherapy is a type of radiotherapy wherein titanium capsules containing therapeutic radioisotopes are implanted within tumor tissues, enabling high-dose radio-irradiation to tumor tissues around the seeds. Although marked therapeutic effects have been demonstrated, brachytherapy needs complicated implantation technique under general anesthesia and the seeds could migrate to other organs. The aim of this study is to establish a novel brachytherapy using biocompatible, injectable thermo-responsive polymers (polyoxazoline; POZ) labeled with yttrium-90 ((90)Y), which can self-aggregate above a specific transition temperature, resulting in long-term intratumoral retention of radioactivity and therapeutic effect...
April 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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