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Laboratory Investigation; a Journal of Technical Methods and Pathology

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https://www.readbyqxmd.com/read/28346400/t-lymphocyte-homing-an-underappreciated-yet-critical-hurdle-for-successful-cancer-immunotherapy
#1
Robert Sackstein, Tobias Schatton, Steven R Barthel
Advances in cancer immunotherapy have offered new hope for patients with metastatic disease. This unfolding success story has been exemplified by a growing arsenal of novel immunotherapeutics, including blocking antibodies targeting immune checkpoint pathways, cancer vaccines, and adoptive cell therapy (ACT). Nonetheless, clinical benefit remains highly variable and patient-specific, in part, because all immunotherapeutic regimens vitally hinge on the capacity of endogenous and/or adoptively transferred T-effector (Teff) cells, including chimeric antigen receptor (CAR) T cells, to home efficiently into tumor target tissue...
March 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28346399/endothelial-cell-specific-activation-of-transforming-growth-factor-%C3%AE-signaling-in-mice-induces-cutaneous-visceral-and-microvascular-fibrosis
#2
Peter J Wermuth, Kellan R Carney, Fabian A Mendoza, Sonsoles Piera-Velazquez, Sergio A Jimenez
In this study, we tested the hypothesis that constitutive endothelial cell-specific activation of TGF-β signaling induces tissue fibrosis and vasculopathy resembling the characteristic fibrotic and vascular alterations of systemic sclerosis. Transgenic mice with inducible expression of a constitutively active TGF-β receptor I specifically in endothelial cells were generated by intercrossing mice harboring a constitutively active TGF-β receptor I with a mouse strain containing the endothelial cell-specific Cdh5 gene promoter directing the tamoxifen-inducible expression of the Cre-ER(T2) cassette...
March 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28319086/cytochrome-p450-cyp-epoxygenases-as-potential-targets-in-the-management-of-impaired-diabetic-wound-healing
#3
Huichen Zhao, Jicui Chen, Jiachao Chai, Yuchao Zhang, Cong Yu, Zhe Pan, Peng Gao, Chen Zong, Qingbo Guan, Yuqin Fu, Yuantao Liu
Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In the present study, we aimed to explore the role and effects of CYP epoxygenases/EETs in wound healing in ob/ob mice. Full-thickness skin dorsal wounds were made on ob/ob mice and C57BL/6 control mice. The mRNA and protein expression of CYP epoxygenases were determined in granulation tissues of wounds. Effects of EETs on wound healing were evaluated...
March 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28287635/efficient-production-of-trophoblast-lineage-cells-from-human-induced-pluripotent-stem-cells
#4
Junya Kojima, Atsushi Fukuda, Hayato Taira, Tomoyuki Kawasaki, Hiroe Ito, Naoaki Kuji, Keiichi Isaka, Akihiro Umezawa, Hidenori Akutsu
Human induced pluripotent stem cells (hiPSCs) are potentially useful in both clinical applications and basic biological research. hiPSCs can differentiate into extra-embryonic cells in the presence of BMP4. However, the differentiation potential of hiPSCs can be affected by culture conditions or genetic variation. In this study, we investigated the effect of various BMP4 concentrations on the expression states of trophoblast markers and the optimal conditions for trophoblast induction. A high-fidelity gene expression assay using hiPSC lines showed that the expression levels of various trophoblast marker genes, such as KRT7, GCM1, CGB, and HLA-G, were upregulated by BMP4 in a dose-dependent manner in all types of hiPSCs used in this study...
March 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28287634/immune-microenvironment-of-gliomas
#5
Anna Gieryng, Dominika Pszczolkowska, Kacper A Walentynowicz, Wenson D Rajan, Bozena Kaminska
High-grade gliomas are rapidly progressing tumors of the central nervous system (CNS) with a very poor prognosis despite extensive resection combined with radiation and/or chemotherapy. Histopathological and flow cytometry analyses of human and rodent experimental gliomas revealed heterogeneity of a tumor and its niche, composed of reactive astrocytes, endothelial cells, and numerous immune cells. Infiltrating immune cells consist of CNS resident (microglia) and peripheral macrophages, granulocytes, myeloid-derived suppressor cells (MDSCs), and T lymphocytes...
March 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28287633/increased-vasohibin-1-expression-is-associated-with-metastasis-and-poor-prognosis-of-renal-cell-carcinoma-patients
#6
Shuji Mikami, Mototsugu Oya, Takeo Kosaka, Ryuichi Mizuno, Yasumasa Miyazaki, Yasufumi Sato, Yasunori Okada
The microvascular density detected by markers of endothelial cells (ECs), such as CD31 and CD34, is considered to be a biomarker for angiogenesis, and it is generally associated with the malignant potential of solid tumors. However, there is a conflicting relationship between the microvascular density and prognosis in clear-cell renal cell carcinoma (ccRCC) patients. It may be explained by the suggestion that the microvascular density cannot fully reflect the angiogenic activity in ccRCC, as the markers of ECs are expressed by both quiescent and activated ECs...
March 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28263294/increased-expression-of-latent-tgf-%C3%AE-binding-protein-4-affects-the-fibrotic-process-in-scleroderma-by-tgf-%C3%AE-smad-signaling
#7
Jiaying Lu, Qingmei Liu, Lei Wang, Wenzhen Tu, Haiyan Chu, Weifeng Ding, Shuai Jiang, Yanyun Ma, Xiangguang Shi, Weilin Pu, Xiaodong Zhou, Li Jin, Jiucun Wang, Wenyu Wu
Scleroderma is a fibrosis-related disorder characterized by cutaneous and internal organ fibrosis, and excessive collagen deposition in extracellular matrix (ECM) is a major cause of fibrosis. Transforming growth factor-β (TGF-β)/SMAD signaling has a central role in the pathogenesis of fibrosis by inducing abnormal collagen accumulation in ECM, and latent TGF-β-binding protein 4 (LTBP-4) affects the secretion of latent TGF-β to ECM. A previous study indicated that bleomycin (BLM) treatment increased LTBP-4 expression in lung fibroblasts of Thy-1 knockout mice with lung fibrosis, and LTBP-4 further promoted TGF-β bioavailability as well as SMAD3 phosphorylation...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28263293/advanced-oxidation-protein-products-promote-nadph-oxidase-dependent-%C3%AE-cell-destruction-and-dysfunction-through-the-bcl-2-bax-apoptotic-pathway
#8
Min Liang, Aiqing Li, Aiju Lou, Xifang Zhang, Youyuan Chen, Lei Yang, Yumin Li, Shenglin Yang, Fan Fan Hou
The accumulation of plasma advanced oxidation protein products (AOPPs) has been linked with diverse disorders, including diabetes, chronic kidney disease, obesity, and metabolic syndrome. The aim of the present study was to evaluate the pathophysiological relevance of AOPPs in β-cell destruction and dysfunction. Exposure of cultured rat β-cells (INS-1) to AOPPs induced an increase in Bax expression, caspase-3 activity, and apoptosis as well as a decrease in Bcl-2 expression in a dose- and time-dependent manner...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28263292/the-master-role-of-microphthalmia-associated-transcription-factor-in-melanocyte-and-melanoma-biology
#9
Akinori Kawakami, David E Fisher
Certain transcription factors have vital roles in lineage development, including specification of cell types and control of differentiation. Microphthalmia-associated transcription factor (MITF) is a key transcription factor for melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes to promote melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis, including genes encoding proteins involved in apoptosis (eg, BCL2) and the cell cycle (eg, CDK2)...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28263291/iron-suppresses-erythropoietin-expression-via-oxidative-stress-dependent-hypoxia-inducible-factor-2-alpha-inactivation
#10
Keisuke Oshima, Yasumasa Ikeda, Yuya Horinouchi, Hiroaki Watanabe, Hirofumi Hamano, Yoshitaka Kihira, Seiji Kishi, Yuki Izawa-Ishizawa, Licht Miyamoto, Tasuku Hirayama, Hideko Nagasawa, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
Renal anemia is a major complication in chronic kidney disease (CKD). Iron supplementation, as well as erythropoiesis-stimulating agents, are widely used for treatment of renal anemia. However, excess iron causes oxidative stress via the Fenton reaction, and iron supplementation might damage remnant renal function including erythropoietin (EPO) production in CKD. EPO gene expression was suppressed in mice following direct iron treatment. Hypoxia-inducible factor-2 alpha (HIF-2α), a positive regulator of the EPO gene, was also diminished in the kidney of mice following iron treatment...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28263290/blue-intensity-matters-for-cell-cycle-profiling-in-fluorescence-dapi-stained-images
#11
Anabela Ferro, Tânia Mestre, Patrícia Carneiro, Ivan Sahumbaiev, Raquel Seruca, João M Sanches
In the past decades, there has been an amazing progress in the understanding of the molecular mechanisms of the cell cycle. This has been possible largely due to a better conceptualization of the cycle itself, but also as a consequence of technological advances. Herein, we propose a new fluorescence image-based framework targeted at the identification and segmentation of stained nuclei with the purpose to determine DNA content in distinct cell cycle stages. The method is based on discriminative features, such as total intensity and area, retrieved from in situ stained nuclei by fluorescence microscopy, allowing the determination of the cell cycle phase of both single and sub-population of cells...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28263289/establishment-of-a-mouse-model-of-enalapril-induced-liver-injury-and-investigation-of-the-pathogenesis
#12
Yuji Shirai, Shingo Oda, Sayaka Makino, Koichi Tsuneyama, Tsuyoshi Yokoi
Drug-induced liver injury (DILI) is a major concern in drug development and clinical drug therapy. Since the underlying mechanisms of DILI have not been fully understood in most cases, elucidation of the hepatotoxic mechanisms of drugs is expected. Although enalapril (ELP), an angiotensin-converting enzyme inhibitor, has been reported to cause liver injuries with a low incidence in humans, the precise mechanisms by which ELP causes liver injury remains unknown. In this study, we established a mouse model of ELP-induced liver injury and analyzed the mechanisms of its hepatotoxicity...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28240749/regression-in-primary-cutaneous-melanoma-etiopathogenesis-and-clinical-significance
#13
Phyu P Aung, Priyadharsini Nagarajan, Victor G Prieto
Though not required currently for staging, regression is a histopathologic parameter typically reported upon diagnosis of an invasive primary cutaneous melanoma. The studies examining the prognostic significance of regression in patient outcome have yielded controversial findings; likely because the definition and assessment of regression have not been consistent, in addition to subjectivity of pathologists' interpretation. Regression is histologically characterized by variable decrease in the number of melanoma cells accompanied by the presence of a host response consisting of dermal fibrosis, inflammatory infiltrate, melanophages, ectatic blood vessels, epidermal attenuation, and/or apoptosis of keratinocytes or melanocytes; the relative extent of these features depends on the stage of the regression...
February 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28240748/drugs-with-anti-oxidant-properties-can-interfere-with-cell-viability-measurements-by-assays-that-rely-on-the-reducing-property-of-viable-cells
#14
Niraj Shenoy, Mary Stenson, Joshua Lawson, Jithma Abeykoon, Mrinal Patnaik, Xiaosheng Wu, Thomas Witzig
Cell viability assays such as Cell Titer Blue and Alamar Blue rely on the reducing property of viable cells to reduce the reagent dye to a product which gives a fluorescent signal. The current manufacture-recommended protocols do not take into account the possibility of the reagent substrate being reduced directly to the fluorescent product by drugs with an anti-oxidant property. After suspecting spurious results while determining the cytotoxic potential of a drug of interest (DOI) with known anti-oxidant property against a renal cell cancer (RCC) cell line, we aimed to establish that drugs with anti-oxidant property can indeed cause false-negative results with the current protocols of these assays by direct reduction of the reagent substrate...
February 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28240747/antibodies-against-nonstructural-protein-1-protect-mice-from-dengue-virus-induced-mast-cell-activation
#15
Ya-Ting Chu, Shu-Wen Wan, Yu-Chang Chang, Chien-Kuo Lee, Betty A Wu-Hsieh, Robert Anderson, Yee-Shin Lin
Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). DHF/DSS patients have been reported to have increased levels of urinary histamine, chymase, and tryptase, which are major granule-associated mediators from mast cells. Previous studies also showed that DENV-infected human mast cells induce production of proinflammatory cytokines and chemokines, suggesting a role played by mast cells in vascular perturbation as well as leukocyte recruitment. In this study, we show that DENV but not UV-inactivated DENV enhanced degranulation of mast cells and production of chemokines (MCP-1, RANTES, and IP-10) in a mouse model...
February 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28240746/epithelial-mesenchymal-transition-promotes-sox2-and-nanog-expression-in-bladder-cancer
#16
Toshiro Migita, Ayano Ueda, Tomokazu Ohishi, Megumi Hatano, Hiroyuki Seimiya, Shin-Ichiro Horiguchi, Fumitaka Koga, Futoshi Shibasaki
Bladder cancer is the most common malignant tumor of the urothelium and is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Stemness markers such as SOX2 and NANOG are frequently overexpressed in various aggressive cancers, including MIBC; epithelial-mesenchymal transition (EMT) has been proposed as a potential trigger of stemness in cancers. To determine whether cancer stemness is acquired via EMT in bladder cancer, we studied the effect of EMT on the expression of SOX2 and NANOG in bladder cancer cell lines...
February 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28240745/the-biological-and-prognostic-significance-of-angiotropism-in-uveal-melanoma
#17
Raymond L Barnhill, Mengliang Ye, Aude Batistella, Marc-Henri Stern, Sergio Roman-Roman, Rémi Dendale, Olivier Lantz, Sophie Piperno-Neumann, Laurence Desjardins, Nathalie Cassoux, Claire Lugassy
Angiotropism is a marker of extravascular migration of melanoma cells along vascular and other structures and a prognostic factor in cutaneous melanoma. Because of this biological and prognostic importance in cutaneous melanoma, angiotropism was studied in uveal melanoma (UM). This retrospective study performed at a single ocular oncology referral center included 89 patients from the study period 2006-2008. All patients were diagnosed with UM from the choroid and/or ciliary body. All patients underwent enucleation for prognostic purposes and definitive therapy...
February 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28218743/vitamin-d-signaling-and-melanoma-role-of-vitamin-d-and-its-receptors-in-melanoma-progression-and-management
#18
REVIEW
Andrzej T Slominski, Anna A Brożyna, Michal A Zmijewski, Wojciech Jóźwicki, Anton M Jetten, Rebecca S Mason, Robert C Tuckey, Craig A Elmets
Ultraviolet B (UVB), in addition to having carcinogenic activity, is required for the production of vitamin D3 (D3) in the skin which supplies >90% of the body's requirement. Vitamin D is activated through hydroxylation by 25-hydroxylases (CYP2R1 or CYP27A1) and 1α-hydroxylase (CYP27B1) to produce 1,25(OH)2D3, or through the action of CYP11A1 to produce mono-di- and trihydroxy-D3 products that can be further modified by CYP27B1, CYP27A1, and CYP24A1. The active forms of D3, in addition to regulating calcium metabolism, exert pleiotropic activities, which include anticarcinogenic and anti-melanoma effects in experimental models, with photoprotection against UVB-induced damage...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28218742/mirna-expression-profiles-reveal-the-involvement-of-mir-26a-mir-548l-and-mir-34a-in-hepatocellular-carcinoma-progression-through-regulation-of-st3gal5
#19
Hongjiao Cai, Huimin Zhou, Yuan Miao, Nana Li, Lifen Zhao, Li Jia
MicroRNAs (miRNAs) have key roles in comprehensive physiological and pathological processes by targeting specific genes through translational repression. Identification of miRNAs related to metastasis enables us to obtain better insight into cancer development. In the current study, we investigated the miRNA expressional profiles in the highly invasive human hepatocellular carcinoma cell line MHCC97-H and MHCC97-L with lower metastatic potential using miRNA microarrays. By quantitative real-time PCR, we confirmed the results of miRNA experiments...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28218741/identification-of-micrornas-associated-with-invasive-and-aggressive-phenotype-in-cutaneous-melanoma-by-next-generation-sequencing
#20
Sankhiros Babapoor, Rong Wu, James Kozubek, Donna Auidi, Jane M Grant-Kels, Soheil S Dadras
A comprehensive repertoire of human microRNAs (miRNAs) that could be involved in early melanoma invasion into the dermis remains unknown. To this end, we sequenced small RNAs (18-30 nucleotides) isolated from an annotated series of invasive melanomas (average invasive depth, 2.0 mm), common melanocytic nevi, and matched normal skin (n=28). Our previously established bioinformatics pipeline identified 765 distinct mature known miRNAs and defined a set of top 40 list that clearly segregated melanomas into thin (0...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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