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Laboratory Investigation; a Journal of Technical Methods and Pathology

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https://www.readbyqxmd.com/read/29155424/immune-checkpoint-inhibitors-in-sarcomas-in-quest-of-predictive-biomarkers
#1
Robin Veenstra, Marie Kostine, Anne-Marie Cleton-Jansen, Noel Fcc de Miranda, Judith Vmg Bovée
Sarcomas are a rare group of tumors of mesenchymal origin. Metastatic sarcomas are often difficult to treat and unresponsive to standard radio- and chemotherapy, resulting in a poor survival rate for patients. Novel treatments with immune checkpoint inhibitors have been proven to prolong survival of patients with a variety of cancers, including metastatic melanoma, lung, and renal cell carcinoma. Since immune checkpoint inhibitors could provide a novel treatment option for patients with sarcomas, clinical trials investigating their efficacy in these group of tumors are ongoing...
November 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29155423/experimental-models-of-pancreatic-cancer-desmoplasia
#2
Sujit Suklabaidya, Pujarini Dash, Biswajit Das, Voddu Suresh, Prakash K Sasmal, Shantibhusan Senapati
Desmoplasia is a fibro-inflammatory process and a well-established feature of pancreatic cancer. A key contributor to pancreatic cancer desmoplasia is the pancreatic stellate cell. Various in vitro and in vivo methods have emerged for the isolation, characterization, and use of pancreatic stellate cells in models of cancer-associated fibrosis. In addition to cell culture models, genetically engineered animal models have been established that spontaneously develop pancreatic cancer with desmoplasia. These animal models are currently being used for the study of pancreatic cancer pathogenesis and for evaluating therapeutics against pancreatic cancer...
November 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29131161/rapid-virtual-hematoxylin-and-eosin-histology-of-breast-tissue-specimens-using-a-compact-fluorescence-nonlinear-microscope
#3
Lucas C Cahill, Michael G Giacomelli, Tadayuki Yoshitake, Hilde Vardeh, Beverly E Faulkner-Jones, James L Connolly, Chi-Kuang Sun, James G Fujimoto
Up to 40% of patients undergoing breast conserving surgery for breast cancer require repeat surgeries due to close to or positive margins. The lengthy processing required for evaluating surgical margins by standard paraffin-embedded histology precludes its use during surgery and therefore, technologies for rapid evaluation of surgical pathology could improve the treatment of breast cancer by reducing the number of surgeries required. We demonstrate real-time histological evaluation of breast cancer surgical specimens by staining specimens with acridine orange (AO) and sulforhodamine 101 (SR101) analogously to hematoxylin and eosin (H&E) and then imaging the specimens with fluorescence nonlinear microscopy (NLM) using a compact femtosecond fiber laser...
November 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29106395/nadph-oxidase-4-promotes-cisplatin-induced-acute-kidney-injury-via-ros-mediated-programmed-cell-death-and-inflammation
#4
Xiao-Ming Meng, Gui-Ling Ren, Li Gao, Qin Yang, Hai-Di Li, Wei-Feng Wu, Cheng Huang, Lei Zhang, Xiong-Wen Lv, Jun Li
The goal of this study was to elucidate the functional role of Nox4 during acute kidney injury (AKI). NADPH oxidases are a major source of reactive oxygen species (ROS) in the kidney in normal and pathological conditions. Among NADPH oxidase isoforms, NADPH oxidase4 (Nox4) is highly expressed in the kidney and has an important role in kidney diseases, such as diabetic nephropathy and renal carcinoma. We previously found that Nox4 expression significantly increased in the toxic AKI model. However, its functional role and mechanism of action in AKI are still unknown...
November 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29083412/resolvind1-stimulates-epithelial-wound-repair-and-inhibits-tgf-%C3%AE-induced-emt-whilst-reducing-fibroproliferation-and-collagen-production
#5
Shengxing Zheng, Qian Wang, Vijay D'Souza, Dom Bartis, Rachel Dancer, Dhruv Parekh, Fang Gao, Qingquan Lian, Shengwei Jin, David R Thickett
Acute and chronic inflammatory lung diseases are often associated with epithelial cell injury/loss and fibroproliferative responses. ResolvinD1 (RvD1) is biosynthesized during the resolution phase of inflammatory response and exerts potent anti-inflammatory and promotes resolution of inflammatory lung diseases. The aim of this study was to investigate whether RvD1 exerts protective effects on alveolar epithelial cell function/differentiation and protects against fibroproliferative stimuli. Primary human alveolar type II cells were used to model the effects of RvD1 in vitro upon wound repair, proliferation, apoptosis, transdifferentiation, and epithelial-mesenchymal transition (EMT)...
October 30, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29083411/vascular-endothelial-growth-factor-c-ameliorates-renal-interstitial-fibrosis-through-lymphangiogenesis-in-mouse-unilateral-ureteral-obstruction
#6
Shoko Hasegawa, Toshiaki Nakano, Kumiko Torisu, Akihiro Tsuchimoto, Masahiro Eriguchi, Naoki Haruyama, Kosuke Masutani, Kazuhiko Tsuruya, Takanari Kitazono
Renal fibrosis is the final common pathway of chronic kidney diseases. Lymphatic vessel (LV) proliferation is found in human renal diseases and other fibrotic diseases, suggesting that lymphangiogenesis is associated with the progression or suppression of kidney diseases. However, the purpose of LV proliferation is not completely understood. We investigated the effect of vascular endothelial growth factor (VEGF)-C on lymphangiogenesis, inflammation, and fibrosis in the mouse kidney using the unilateral ureteral obstruction (UUO) model...
October 30, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29083410/nm23-ndpk-proteins-in-transcription-regulatory-functions-and-chromatin-modulation-emerging-trends
#7
Shalu Sharma, Antara Sengupta, Shantanu Chowdhury
NM23/NDPK proteins have been studied for their metastasis suppressor role but the molecular pathways involved in this process are not very vivid. Nucleotide binding and kinase activities of NM23 proteins implicated in anti-metastatic effects have been widely studied. In addition to these, transcriptional regulation adds another arm to the versatility of NM23 proteins that together with the other functions may contribute to better understanding of underlying mechanisms. In this review we discuss emerging reports describing the role of NM23 proteins in gene regulation and chromatin modulation in association with other factors or on their own...
October 30, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29058707/balance-of-cardiac-and-systemic-hepcidin-and-its-role-in-heart-physiology-and-pathology
#8
Driton Vela
Hepcidin is the main regulator of iron metabolism in tissues. Its serum levels are mostly correlated with the levels of hepcidin expression from the liver, but local hepcidin can be important for the physiology of other organs as well. There is an increasing evidence that this is the case with cardiac hepcidin. This has been confirmed by studies with models of ischemic heart disease and other heart pathologies. In this review the discussion dissects the role of cardiac hepcidin in cellular homeostasis. This review is complemented with examination of the role of systemic hepcidin in heart disease and its use as a biochemical marker...
October 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29058706/histidine-kinases-and-the-missing-phosphoproteome-from-prokaryotes-to-eukaryotes
#9
Kevin Adam, Tony Hunter
Protein phosphorylation is the most common type of post-translational modification in eukaryotes. The phosphoproteome is defined as the complete set of experimentally detectable phosphorylation sites present in a cell's proteome under various conditions. However, we are still far from identifying all the phosphorylation sites in a cell mainly due to the lack of information about phosphorylation events involving residues other than Ser, Thr and Tyr. Four types of phosphate-protein linkage exist and these generate nine different phosphoresidues-pSer, pThr, pTyr, pHis, pLys, pArg, pAsp, pGlu and pCys...
October 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29058705/identification-of-a-gene-expression-signature-associated-with-the-metastasis-suppressor-function-of-nme1-prognostic-value-in-human-melanoma
#10
M Kathryn Leonard, Joseph R McCorkle, Devin E Snyder, Marian Novak, Qingbei Zhang, Amol C Shetty, Anup A Mahurkar, David M Kaetzel
Although NME1 is well known for its ability to suppress metastasis of melanoma, the molecular mechanisms underlying this activity are not completely understood. Herein, we utilized a bioinformatics approach to systematically identify genes whose expression is correlated with the metastasis suppressor function of NME1. This was accomplished through a search for genes that were regulated by NME1, but not by NME1 variants lacking metastasis suppressor activity. This approach identified a number of novel genes, such as ALDOC, CXCL11, LRP1b, and XAGE1 as well as known targets such as NETO2, which were collectively designated as an NME1-Regulated Metastasis Suppressor Signature (MSS)...
October 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29058704/nuclear-functions-of-nme-proteins
#11
Gemma S Puts, M Kathryn Leonard, Nidhi V Pamidimukkala, Devin E Snyder, David M Kaetzel
The NME family of proteins is composed of 10 isoforms, designated NME1-10, which are diverse in their enzymatic activities and patterns of subcellular localization. Each contains a conserved domain associated with a nucleoside diphosphate kinase (NDPK) function, although not all are catalytically active. Several of the NME isoforms (NME1, NME5, NME7, and NME8) also exhibit a 3'-5' exonuclease activity, suggesting roles in DNA proofreading and repair. NME1 and NME2 have been shown to translocate to the nucleus, although they lack a canonical nuclear localization signal...
October 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035383/extracellular-nme-proteins-a-player-or-a-bystander
#12
Patrizia Romani, Marilena Ignesti, Giuseppe Gargiulo, Tien Hsu, Valeria Cavaliere
The Nm23/NME gene family has been under intensive study since Nm23H1/NME1 was identified as the first metastasis suppressor. Inverse correlation between the expression levels of NME1/2 and prognosis has indeed been demonstrated in different tumor cohorts. Interestingly, the presence of NME proteins in the extracellular environment in normal and tumoral conditions has also been noted. In many reported cases, however, these extracellular NME proteins exhibit anti-differentiation or oncogenic functions, contradicting their canonical anti-metastatic action...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035382/regulation-of-heterotrimeric-g-protein-signaling-by-ndpk-nme-proteins-and-caveolins-an-update
#13
Issam H Abu-Taha, Jordi Heijman, Yuxi Feng, Christiane Vettel, Dobromir Dobrev, Thomas Wieland
Heterotrimeric G proteins are pivotal mediators of cellular signal transduction in eukaryotic cells and abnormal G-protein signaling plays an important role in numerous diseases. During the last two decades it has become evident that the activation status of heterotrimeric G proteins is both highly localized and strongly regulated by a number of factors, including a receptor-independent activation pathway of heterotrimeric G proteins that does not involve the classical GDP/GTP exchange and relies on nucleoside diphosphate kinases (NDPKs)...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035381/high-expression-of-hoxa13-correlates-with-poorly-differentiated-hepatocellular-carcinomas-and-modulates-sorafenib-response-in-in-vitro-models
#14
Luca Quagliata, Cristina Quintavalle, Manuela Lanzafame, Matthias S Matter, Chiara Novello, Luca di Tommaso, Tiziana Pressiani, Lorenza Rimassa, Luigi Tornillo, Massimo Roncalli, Clemente Cillo, Pierlorenzo Pallante, Salvatore Piscuoglio, Charlotte Ky Ng, Luigi M Terracciano
Hepatocellular carcinoma (HCC) represents the fifth and ninth cause of mortality among male and female cancer patients, respectively and typically arises on a background of a cirrhotic liver. HCC develops in a multi-step process, often encompassing chronic liver injury, steatosis and cirrhosis eventually leading to the malignant transformation of hepatocytes. Aberrant expression of the class I homeobox gene family (HOX), a group of genes crucial in embryogenesis, has been reported in a variety of malignancies including solid tumors...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035380/mixed-cell-therapy-of-bone-marrow-derived-mesenchymal-stem-cells-and-articular-cartilage-chondrocytes-ameliorates-osteoarthritis-development
#15
Indira Prasadam, Akoy Akuien, Thor E Friis, Wei Fang, Xinzhan Mao, Ross W Crawford, Yin Xiao
Of the many cell-based treatments that have been tested in an effort to regenerate osteoarthritic articular cartilage, none have ever produced cartilage that compare with native hyaline cartilage. Studies show that different cell types lead to inconsistent results and for cartilage regeneration to be considered successful, there must be an absence of fibrotic tissue. Here we report of a series of experiments in which bone marrow-derived stem cells (BMSCs) and articular cartilage chondrocytes (ACCs) were mixed in a 1:1 ratio and tested for their ability to enhance cartilage regeneration in three different conditions: (1) in an in vitro differentiation model; (2) in an ex vivo cartilage defect model implanted subcutaneously in mice; and (3) as an intra-articular injection in a meniscectomy-induced OA model in rats...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035379/lobular-carcinoma-in-situ-and-invasive-lobular-breast-cancer-are-characterized-by-enhanced-expression-of-transcription-factor-ap-2%C3%AE
#16
Mieke Raap, Malte Gronewold, Henriette Christgen, Silke Glage, Mohammad Bentires-Alj, Shany Koren, Patrick W Derksen, Mirjam Boelens, Jos Jonkers, Ulrich Lehmann, Friedrich Feuerhake, Elna Kuehnle, Oleg Gluz, Ronald Kates, Ulrike Nitz, Nadia Harbeck, Hans H Kreipe, Matthias Christgen
Transcription factor AP-2β (TFAP2B) regulates embryonic organ development and is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene expression profiling has implicated AP-2β in breast cancer (BC). This study characterizes AP-2β expression in the mammary gland and in BC. AP-2β protein expression was assessed in the normal mammary gland epithelium, in various reactive, metaplastic and pre-invasive neoplastic lesions and in two clinical BC cohorts comprising >2000 patients. BCs from various genetically engineered mouse (GEM) models were also evaluated...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035378/molecular-similarities-and-differences-from-human-pulmonary-fibrosis-and-corresponding-mouse-model-maldi-imaging-mass-spectrometry-in-comparative-medicine
#17
Michaela Aichler, Thomas Kunzke, Achim Buck, Na Sun, Maximilian Ackermann, Danny Jonigk, Andreas Gaumann, Axel Walch
Animal models can reproduce some model-specific aspects of human diseases, but some animal models translate poorly or fail to translate to the corresponding human disease. Here, we develop a strategy to systematically compare human and mouse tissues, and conduct a proof-of-concept experiment to identify molecular similarities and differences using patients with idiopathic pulmonary fibrosis and a bleomycin-induced fibrosis mouse model. Our novel approach employs high-throughput tissue microarrays (TMAs) of humans and mice, high-resolution matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance-mass spectrometry imaging (MALDI-FT-ICR-MSI) to spatially resolve mass spectra at the level of specific metabolites, and hierarchical clustering and pathway enrichment analysis to identify functionally similar/different molecular patterns and pathways in pathological lesions of humans and mice...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035377/nme4-nucleoside-diphosphate-kinase-d-in-cardiolipin-signaling-and-mitophagy
#18
Uwe Schlattner, Malgorzata Tokarska-Schlattner, Richard M Epand, Mathieu Boissan, Marie-Lise Lacombe, Valerian E Kagan
Mitophagy is an emerging paradigm for mitochondrial quality control and cell homeostasis. Dysregulation of mitophagy can lead to human pathologies such as neurodegenerative disorders and contributes to the aging process. Complex protein signaling cascades have been described that regulate mitophagy. We have identified a novel lipid signaling pathway that involves the phospholipid cardiolipin (CL). CL is synthesized and normally confined at the inner mitochondrial membrane. However, upon a mitophagic trigger, ie, collapse of the inner membrane potential, CL is rapidly externalized to the mitochondrial surface with the assistance of the hexameric nucleoside diphosphate kinase D (NME4, NDPK-D, or NM23-H4)...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035376/oncogenic-epstein-barr-virus-recruits-nm23-h1-to-regulate-chromatin-modifiers
#19
Saurabh Pandey, Erle S Robertson
In cancer progression, metastasis is a major cause of poor survival of patients and can be targeted for therapeutic interventions. The first discovered metastatic-suppressor Nm23-H1 possesses nucleoside diphosphate kinase, histidine kinase, and DNase activity as a broad-spectrum enzyme. Recent advances in cancer metastasis have opened new ways for the development of therapeutic molecular approaches. In this review, we provide a summary of the current understanding of Nm23/NDPKs in the context of viral oncogenesis...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29035375/upregulation-of-the-actin-cytoskeleton-via-myocardin-leads-to-increased-expression-of-type-1-collagen
#20
Zengdun Shi, Don C Rockey
Liver fibrosis, a model wound healing system, is characterized by excessive deposition of extracellular matrix (ECM) in the liver. Although many fibrogenic cell types may express ECM, the hepatic stellate cell (HSC) is currently considered to be the major effector. HSCs transform into myofibroblast-like cells, also known as hepatic myofibroblasts in a process known as activation; this process is characterized in particular by de novo expression of smooth muscle alpha actin (SM α-actin) and type 1 collagen...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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