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https://www.readbyqxmd.com/read/29735551/novel-richter-s-syndrome-xenograft-models-to-study-genetic-architecture-biology-and-therapy-responses
#1
Tiziana Vaisitti, Esteban Braggio, John N Allan, Francesca Arruga, Sara Serra, Alberto Zamò, Wayne Tam, Amy Chadburn, Richard R Furman, Silvia Deaglio
Richter's syndrome (RS) represents the evolution of chronic lymphocytic leukemia into an aggressive tumor, most commonly diffuse large B cell lymphoma. The lack of in vitro and in vivo models has severely hampered drug testing in a disease that is poorly responsive to common chemo-immunotherapeutic combinations as well as to novel kinase inhibitors. Here we report for the first time the establishment and genomic characterization of two patient-derived tumor xenograft models of RS, RS9737 and RS1316. RS xenografts were genetically, morphologically and phenotypically stable and similar to the corresponding primary tumor...
May 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29734873/whole-exome-sequencing-of-sinonasal-small-cell-carcinoma-arising-within-a-papillary-schneiderian-carcinoma-in-situ
#2
Joshua Smith, Aditi Kulkarni, Andrew C Birkeland, Jonathan B McHugh, J Chad Brenner
Objective The pathogenetic underpinnings of extrapulmonary small cell carcinomas (EPSCCs) of the head and neck are poorly understood. We sought to describe the clinical case and whole-exome DNA sequencing data of a patient with sinonasal Schneiderian carcinoma in situ whose tumor progressed to small cell carcinoma (SCC). Study Design Case report and whole-exome sequencing of tumor DNA. Setting Academic medical center. Subjects and Methods A 52-year-old man with sinonasal Schneiderian carcinoma in situ whose tumor progressed to small cell carcinoma...
May 1, 2018: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29732051/dual-targeting-biomimetic-delivery-for-anti-glioma-activity-via-remodeling-the-tumor-microenvironment-and-directing-macrophage-mediated-immunotherapy
#3
Pengfei Zhao, Yonghui Wang, Xuejia Kang, Aihua Wu, Weimin Yin, Yisi Tang, Jinyu Wang, Meng Zhang, Yifei Duan, Yongzhuo Huang
Tumor-associated macrophages (TAMs) are the major components in the tumor microenvironment (TME). The polarization from the protumor M2 (TAM2) to antitumor M1 (TAM1) phenotype can not only lift the immunosuppressive constraints and elicit cytotoxic T-cell immunity but also augment the chemotherapy efficacy. However, the treatment feasibility by TAM modulation in brain tumors and the mechanisms remained unknown. A dual-targeting biomimetic codelivery and treatment strategy was developed for anti-glioma activity...
March 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29731831/prognostic-significance-of-cd68-cd163-and-folate-receptor-%C3%AE-positive-macrophages-in-hepatocellular-carcinoma
#4
Koji Minami, Kiyokazu Hiwatashi, Shinichi Ueno, Masahiko Sakoda, Satoshi Iino, Hiroshi Okumura, Motoyuki Hashiguchi, Yota Kawasaki, Hiroshi Kurahara, Yuko Mataki, Kosei Maemura, Hiroyuki Shinchi, Shoji Natsugoe
Cluster of differentiation (CD)68 may be used as a pan-macrophage or M1 marker, whereas CD163 may be used as an M2 marker. Furthermore, folate receptor (FR)β exhibits an M2-like functional profile. In the present study, CD68 and CD163 were used to evaluate and classify tumor-associated macrophages (TAMs). The expression of CD68, CD163 and FRβ by TAMs in hepatocellular carcinoma (HCC) Tissues was investigated. Samples from 105 patients with HCC were evaluated using immunohistochemistry. The results revealed that CD68 and CD163 overexpression was associated with a worse prognosis...
May 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29721987/trpv4-does-not-regulate-the-distal-retinal-light-response
#5
Oleg Yarishkin, Tam T T Phuong, Monika Lakk, David Križaj
The transient receptor potential vanilloid isoform 4 (TRPV4) functions as polymodal transducer of swelling, heat, stretch, and lipid metabolites, is widely expressed across sensory tissues, and has been implicated in pressure sensing in vertebrate retinas. Although TRPV4 knockout mice exhibit a variety of mechanosensory, nociceptive, and thermo- and osmoregulatory phenotypes, it is not known whether the transmission of light-induced signals in the eye is affected by the loss of TRPV4. We utilized field potentials, a measure of rod and cone signaling, to determine whether TRPV4 impacts on the generation and/or transmission of the photoreceptor light response and neurotransmission...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29712852/revealing-the-specificity-of-regulatory-t-cells-in-murine-autoimmune-diabetes
#6
Allyson Spence, Whitney Purtha, Janice Tam, Shen Dong, Youmin Kim, Chia-Hsin Ju, Teague Sterling, Maki Nakayama, William H Robinson, Jeffrey A Bluestone, Mark S Anderson, Qizhi Tang
Regulatory T cells (Tregs) control organ-specific autoimmunity in a tissue antigen-specific manner, yet little is known about their specificity in a natural repertoire. In this study, we used the nonobese diabetic (NOD) mouse model of autoimmune diabetes to investigate the antigen specificity of Tregs present in the inflamed tissue, the islets of Langerhans. Compared with Tregs present in spleen and lymph node, Tregs in the islets showed evidence of antigen stimulation that correlated with higher proliferation and expression of activation markers CD103, ICOS, and TIGIT...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29708510/tumor-secreted-pros1-inhibits-macrophage-m1-polarization-to-reduce-antitumor-immune-response
#7
Eric Ubil, Laura Caskey, Alisha Holtzhausen, Debra Hunter, Charlotte Story, H Shelton Earp
Tyro3, Axl, Mer (TAM) receptor tyrosine kinases reduce inflammatory, innate immune responses. We demonstrate that tumor-secreted protein S (Pros1), a Mer/Tyro3 ligand, decreased macrophage M1 cytokine expression in vitro and in vivo. In contrast, tumor cells with CRISPR-based deletion of Pros1 failed to inhibit M1 polarization. Tumor cell-associated Pros1 action was abrogated in macrophages from Mer- and Tyro3- but not Axl-KO mice. In addition, several other murine and human tumor cell lines suppressed macrophage M1 cytokine expression induced by IFN-γ and LPS...
April 30, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29706855/actively-targeted-deep-tissue-imaging-and-photothermal-chemo-therapy-of-breast-cancer-by-antibody-functionalized-drug-loaded-x-ray-responsive-bismuth-sulfide-mesoporous-silica-core-shell-nanoparticles
#8
Lihua Li, Yao Lu, Chunyan Jiang, Ye Zhu, Xianfeng Yang, Xiaoming Hu, Zefeng Lin, Yu Zhang, Mingying Peng, Hong Xia, Chuanbin Mao
A theranostic platform combining synergistic therapy and real-time imaging attracts enormous attention but still faces great challenges, such as tedious modifications and lack of efficient accumulation in tumor. Here, a novel type of theranostic agent, bismuth sulfide@mesoporous silica (Bi2 S3 @ mPS) core-shell nanoparticles (NPs), for targeted image-guided therapy of human epidermal growth factor receptor-2 (HER-2) positive breast cancer is developed. To generate such NPs, polyvinylpyrrolidone decorated rod-like Bi2 S3 NPs are chemically encapsulated with a mesoporous silica (mPS) layer and loaded with an anticancer drug, doxorubicin...
January 31, 2018: Advanced Functional Materials
https://www.readbyqxmd.com/read/29695925/primary-iga-nephropathy-current-challenges-and-future-prospects
#9
REVIEW
Rose S Penfold, Maria Prendecki, Stephen McAdoo, Frederick Wk Tam
IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, exhibiting a variable clinical and pathological course and significantly contributing to the global burden of chronic kidney disease and end-stage renal disease. Current standards of care focus on optimization of antihypertensive and antiproteinuric therapies (typically renin- angiotensin system blockade) to reduce disease progression. Much recent attention has focused on whether additional immunosuppression confers better outcomes than supportive management alone, and indeed, several trials have demonstrated renoprotective effects following the use of oral corticosteroids...
2018: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/29691294/reciprocal-network-between-cancer-stem-like-cells-and-macrophages-facilitates-the-progression-and-androgen-deprivation-therapy-resistance-of-prostate-cancer
#10
Hai Huang, Chao Wang, Fei Liu, Hui-Zhen Li, Guang Peng, Xu Gao, Ke-Qin Dong, Hong-Ru Wang, De-Pei Kong, Min Qu, Li-He Dai, Kai-Jian Wang, Zhe Zhou, Jun Yang, Ze-Yu Yang, Yan-Qiong Cheng, Qin-Qin Tian, Dan Liu, Chuan-Liang Xu, Dan-Feng Xu, Xin-Gang Cui, Ying-Hao Sun
PURPOSE: Cancer stem-like cells (CSCs) contribute to the progression and androgen deprivation therapy (ADT) resistance of prostate cancer. Since CSCs depend on their specific niche, including tumor-associated macrophages (TAMs), elucidating the network between CSCs and TAMs may help to effectively inhibit the progression and ADT resistance of prostate cancer. EXPERIMENTAL DESIGN: The underlying intracellular mechanism that sustains the stem-like characteristics of CSCs in prostate cancer was assessed via RNA-seq, co-IP, ChIP and other assays...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29690747/tumor-associated-macrophages-derived-tgf-%C3%AE-%C3%A2-induced-epithelial-to-mesenchymal-transition-in-colorectal-cancer-cells-through-smad2-3-4-snail-signaling-pathway
#11
Jianhui Cai, Limin Xia, Jinlei Li, Shichang Ni, Huayu Song, Xiangbin Wu
Purpose: We investigated the role of tumor-associated macrophages (TAMs) on the epithelial to mesenchymal transition (EMT) of colorectal cancer cells and determined the potential mechanism involved in the metastatic process. Materials and Methods: In this study, flow cytometry was used to detect the expression of target proteins. We used transwell assay to evaluate the migration of cancer cells under specific conditions. Using real-time polymerase chain reaction, we examined the expressions of cytokines and EMT-related markers in mRNA level...
April 25, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29689559/molecular-regulation-of-bone-metastasis-pathogenesis
#12
Meng-Yu Wu, Chia-Jung Li, Giou-Teng Yiang, Yeung-Leung Cheng, Andy Po-Yi Tsai, Yueh-Tseng Hou, Yu-Chieh Ho, Ming-Feng Hou, Pei-Yi Chu
Distant metastases are the major cause of mortality in cancer patients. Bone metastases may cause bone fractures, local pain, hypercalcemia, bone marrow aplasia, and spinal cord compression. Therefore, the management of bone metastases is important in cancer treatment. Normal bone remodeling is regulated by osteoprotegerin ligand (OPGL), receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and other cytokines. In the tumor microenvironment, tumor cells induce a vicious cycle that promotes osteoblastic and osteolytic lesions...
April 18, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29680383/tumour-associated-macrophages-relation-with-progression-and-invasiveness-and-assessment-of-m1-m2-macrophages-in-canine-mammary-tumours
#13
L N Monteiro, M A Rodrigues, D A Gomes, B S Salgado, G D Cassali
Macrophages represent a major component of the overall leucocyte population within neoplasms and are important for tumour behaviour in several cancers in human beings. However, little information regarding their role in canine mammary tumours (CMTs) is available. The aim of this study was to address the potential role of tumour-associated macrophages (TAMs) in CMTs. TAMs in CMTs excised from 82 female dogs were quantified at high power (400× magnification) and categorised as low (≤50) or high (>50) TAM counts...
April 2018: Veterinary Journal
https://www.readbyqxmd.com/read/29670110/tumor-associated-macrophages-promote-progression-and-the-warburg-effect-via-ccl18-nf-kb-vcam-1-pathway-in-pancreatic-ductal-adenocarcinoma
#14
Huilin Ye, Quanbo Zhou, Shangyou Zheng, Guolin Li, Qing Lin, Lusheng Wei, Zhiqiang Fu, Bin Zhang, Yimin Liu, Zhihua Li, Rufu Chen
Tumor-associated macrophages (TAMs) are frequently found near pancreatic cancer cells, but it is uncertain whether they are involved in pancreatic cancer progression and the Warburg effect. Here, we show that CCL18 secreted by TAMs facilitates malignant progression and induced a glycolytic phenotype in pancreatic cancer, partially owing to paracrine induction of VCAM-1 in pancreatic cancer cells. Reciprocally, VCAM-1-induced lactate production from pancreatic cancer cells with enhanced aerobic glycolysis activates macrophages to a TAM-like phenotype, forming a positive feedback loop...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29667169/expression-of-scavenger-receptor-marco-defines-a-targetable-tumor-associated-macrophage-subset-in-non-small-cell-lung-cancer
#15
Linnéa La Fleur, Vanessa F Boura, Andrey Alexeyenko, Anders Berglund, Victor Pontén, Johanna Sm Mattsson, Dijana Djureinovic, Johan Persson, Hans Brunnström, Johan Isaksson, Eva Brandén, Hirsh Koyi, Patrick Micke, Mikael Ci Karlsson, Johan Botling
Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n=352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n=199) with available RNA-seq data...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29643229/t-cell-induced-csf1-promotes-melanoma-resistance-to-pd1-blockade
#16
Natalie J Neubert, Martina Schmittnaegel, Natacha Bordry, Sina Nassiri, Noémie Wald, Christophe Martignier, Laure Tillé, Krisztian Homicsko, William Damsky, Hélène Maby-El Hajjami, Irina Klaman, Esther Danenberg, Kalliopi Ioannidou, Lana Kandalaft, George Coukos, Sabine Hoves, Carola H Ries, Silvia A Fuertes Marraco, Periklis G Foukas, Michele De Palma, Daniel E Speiser
Colony-stimulating factor 1 (CSF1) is a key regulator of monocyte/macrophage differentiation that sustains the protumorigenic functions of tumor-associated macrophages (TAMs). We show that CSF1 is expressed in human melanoma, and patients with metastatic melanoma have increased CSF1 in blood compared to healthy subjects. In tumors, CSF1 expression correlated with the abundance of CD8+ T cells and CD163+ TAMs. Human melanoma cell lines consistently produced CSF1 after exposure to melanoma-specific CD8+ T cells or T cell-derived cytokines in vitro, reflecting a broadly conserved mechanism of CSF1 induction by activated CD8+ T cells...
April 11, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29615760/human-sertoli-cells-support-high-levels-of-zika-virus-replication-and-persistence
#17
Anil Kumar, Juan Jovel, Joaquin Lopez-Orozco, Daniel Limonta, Adriana M Airo, Shangmei Hou, Iryna Stryapunina, Chad Fibke, Ronald B Moore, Tom C Hobman
Zika virus is a teratogenic mosquito-transmitted flavivirus that is associated with birth defects in newborns and Guillain-Barré syndrome in adults. The virus can also be sexually transmitted, but currently, very little is known about the cell types supporting virus replication and persistence in human testes. Using primary cell cultures, we observed that Sertoli but not Leydig cells are highly susceptible to Zika virus infection, a process that is dependent on the TAM family receptor Axl. In cell culture, Sertoli cells could be productively infected with Zika virus for at least 6-weeks...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29593009/stanniocalcin-expression-as-a-predictor-of-late-breast-cancer-recurrence
#18
Kristen D Brantley, Anders Kjærsgaard, Deirdre Cronin-Fenton, Rami Yacoub, Anja S Nielsen, Kristina L Lauridsen, Stephen Hamilton-Dutoit, Timothy L Lash
BACKGROUND: Expression of human paracrine hormones stanniocalcin 1 (STC1) and stanniocalcin 2 (STC2) may potentiate late breast cancer recurrence. We tested the hypothesis that expression of STC1 and STC2 in primary breast tumors is more strongly associated with late versus early recurrences. METHODS: 541 estrogen receptor positive, tamoxifen treated (ER+/TAM+) and 300 estrogen receptor negative, tamoxifen untreated (ER-/TAM-) breast cancer patients who experienced recurrence within ten years of primary diagnosis and matched recurrence-free controls were selected from a cohort of 11,251 Danish breast cancer patients diagnosed with stage I, II, or III breast cancer during 1985-2001...
March 28, 2018: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29592948/tcl1a-a-novel-transcription-factor-and-a-co-regulator-of-nf-%C3%B0%C2%BAb-p65-snp-and-estrogen-dependence
#19
Ming-Fen Ho, Edroaldo Lummertz da Rocha, Cheng Zhang, James Ingle, Paul Goss, Lois Shepherd, Michiaki Kubo, Liewei Wang, Hu Li, Richard Weinshilboum
TCL1A single nucleotide polymorphisms (SNPs) have been associated with aromatase inhibitor-induced musculoskeletal adverse events. We previously demonstrated that TCL1A is estradiol (E2) inducible and plays a critical role in the regulation of cytokines, chemokines and toll like receptors in a TCL1A SNP genotype and estrogen-dependent fashion. Furthermore, TCLIA SNP-dependent expression phenotypes can be "reversed" by exposure to selective estrogen receptor modulators, e.g, 4-hydroxytamoxifen (4OH-TAM)...
March 28, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29578459/the-relationship-between-serum-e2-levels-and-recurrence-in-premenopausal-er-positive-breast-cancer-patients-a-retrospective-study
#20
Haruko Takuwa, Shigehira Saji, Masahiro Takada, Sachiko Takahara, Akira Yamauchi
BACKGROUND: Among estrogens, estradiol (E2) has the strongest physiological activity as a stimulator in estrogen receptor (ER)-positive breast cancer. The aim of this study is to investigate E2 dynamics during endocrine therapy and to explore the optimal environment in which tamoxifen (TAM) exhibits better efficacy for ER-positive premenopausal early breast cancer patients. METHODS: This is a retrospective study enrolled 194 patients with premenopausal ER-positive early-stage breast cancer who aging ≤45 years at onset and receiving luteinizing hormone-releasing hormone-agonist (LHRH-a) and TAM-therapy...
March 19, 2018: Breast Disease
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