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Laboratory Investigation; a Journal of Technical Methods and Pathology

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https://www.readbyqxmd.com/read/28092366/malignant-melanoma-of-sun-protected-sites-a-review-of-clinical-histological-and-molecular-features
#1
Emily A Merkel, Pedram Gerami
In most cases of cutaneous melanoma, ultraviolet (UV) radiation is recognized as a prominent risk factor. Less is known regarding the mechanisms of mutagenesis for melanoma arising in sun-protected sites, such as acral and mucosal melanoma. Acral and mucosal melanoma share many common features, including a late age of onset, a broad radial growth phase with prominent lentiginous growth, the presence of field cancerization cells, and, in most cases, lack of a precursor nevus. In addition to early chromosomal instability, many of the same genes are also involved in these two distinct melanoma subtypes...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28092365/cancer-cell-chemokines-direct-chemotaxis-of-activated-stellate-cells-in-pancreatic-ductal-adenocarcinoma
#2
Ishan Roy, Kathleen A Boyle, Emily P Vonderhaar, Noah P Zimmerman, Egal Gorse, A Craig Mackinnon, Rosa F Hwang, Janusz Franco-Barraza, Edna Cukierman, Susan Tsai, Douglas B Evans, Michael B Dwinell
The mechanisms by which the extreme desmoplasia observed in pancreatic tumors develops remain unknown and its role in pancreatic cancer progression is unsettled. Chemokines have a key role in the recruitment of a wide variety of cell types in health and disease. Transcript and protein profile analyses of human and murine cell lines and human tissue specimens revealed a consistent elevation in the receptors CCR10 and CXCR6, as well as their respective ligands CCL28 and CXCL16. Elevated ligand expression was restricted to tumor cells, whereas receptors were in both epithelial and stromal cells...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28092364/proof-of-the-quantitative-potential-of-immunofluorescence-by-mass-spectrometry
#3
Maria I Toki, Fabiola Cecchi, Todd Hembrough, Konstantinos N Syrigos, David L Rimm
Protein expression in formalin-fixed, paraffin-embedded patient tissue is routinely measured by Immunohistochemistry (IHC). However, IHC has been shown to be subject to variability in sensitivity, specificity and reproducibility, and is generally, at best, considered semi-quantitative. Mass spectrometry (MS) is considered by many to be the criterion standard for protein measurement, offering high sensitivity, specificity, and objective molecular quantification. Here, we seek to show that quantitative immunofluorescence (QIF) with standardization can achieve quantitative results comparable to MS...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28092363/mouse-models-of-uv-induced-melanoma-genetics-pathology-and-clinical-relevance
#4
Chi-Ping Day, Rachel Marchalik, Glenn Merlino, Helen Michael
Melanocytes, a neural crest cell derivative, produce pigment to protect keratinocytes from ultraviolet radiation (UVR). Although melanocytic lesions such as nevi and cutaneous malignant melanomas are known to be associated with sun exposure, the role of UVR in oncogenesis is complex and has yet to be clearly elucidated. UVR appears to have a direct mutational role in inducing or promoting melanoma formation as well as an indirect role through microenvironmental changes. Recent advances in the modeling of human melanoma in animals have built platforms upon which prospective studies can begin to investigate these questions...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28092362/the-role-of-endothelial-hif-1-%C3%AE-in-the-response-to-sublethal-hypoxia-in-c57bl-6-mouse-pups
#5
Qi Li, Michael Michaud, Chan Park, Yan Huang, Rachael Couture, Frank Girodano, Michael L Schwartz, Joseph A Madri
Chronic sublethal hypoxia, a complication of premature birth, is associated with cognitive and motor handicaps. Responsiveness to and recovery from this hypoxic environment is dependent on induction of HIF-1 α in the cells affected. Microvascular endothelial-glial and microvascular endothelial-neuronal precursor interactions have been found to be dynamic and reciprocal, involving autocrine and paracrine signaling, with response and recovery correlated with baseline levels and levels of induction of HIF-1 α...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28067897/pathological-changes-in-basement-membranes-and-dermal-connective-tissue-of-skin-from-patients-with-hereditary-cystatin-c-amyloid-angiopathy
#6
Asbjorg Osk Snorradottir, Helgi J Isaksson, Saevar Ingthorsson, Elias Olafsson, Astridur Palsdottir, Birkir Thor Bragason
Hereditary cystatin C amyloid angiopathy (HCCAA) is a genetic disease caused by a mutation in the cystatin C gene. Cystatin C is abundant in cerebrospinal fluid and the most prominent pathology in HCCAA is cerebral amyloid angiopathy due to mutant cystatin C amyloid deposition with associated cerebral hemorrhages, typically in young adult carriers. Analyses of post-mortem brain samples shows that pathological changes are limited to arteries and regions adjacent to arteries. The severity of pathological changes at post-mortem has precluded the elucidation of the evolution of histological changes...
January 9, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28067896/pathogenic-role-of-endogenous-tnf-%C3%AE-in-the-development-of-sj%C3%A3-gren-s-like-sialadenitis-and-secretory-dysfunction-in-non-obese-diabetic-mice
#7
Jing Zhou, Toshihisa Kawai, Qing Yu
Patients with Sjögren's syndrome (SS), an autoimmune disease primarily affecting exocrine glands, exhibit enhanced TNF-α expression in the saliva and salivary glands. However, the precise in vivo role of TNF-α during the initiation and development of SS is not clearly defined. The present study is undertaken to determine the function of endogenously produced TNF-α in the pathogenesis of SS in non-obese diabetic (NOD) mice, a model of this human disease. Administration of a neutralizing anti-TNF-α antibody to female NOD mice during the stage prior to disease onset significantly improved salivary secretion, indicating a remission of clinical symptoms of SS...
January 9, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28067895/the-nf1-gene-in-tumor-syndromes-and-melanoma
#8
Maija Kiuru, Klaus J Busam
Activation of the RAS/MAPK pathway is critical in melanoma. Melanoma can be grouped into four molecular subtypes based on their main genetic driver: BRAF-mutant, NRAS-mutant, NF1-mutant, and triple wild-type tumors. The NF1 protein, neurofibromin 1, negatively regulates RAS proteins through GTPase activity. Germline mutations in NF1 cause neurofibromatosis type I, a common genetic tumor syndrome caused by dysregulation of the RAS/MAPK pathway, ie, RASopathy. Melanomas with NF1 mutations typically occur on chronically sun-exposed skin or in older individuals, show a high mutation burden, and are wild-type for BRAF and NRAS...
January 9, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28067894/unexpected-uvr-and-non-uvr-mutation-burden-in-some-acral-and-cutaneous-melanomas
#9
Robert V Rawson, Peter A Johansson, Nicholas K Hayward, Nicola Waddell, Ann-Marie Patch, Serigne Lo, John V Pearson, John F Thompson, Graham J Mann, Richard A Scolyer, James S Wilmott
Ultraviolet radiation (UVR) mutagenesis causes nearly all cutaneous melanomas, however, since UVR signatures are largely absent in acral melanoma, as well as melanoma in sun-protected sites, the cause of these melanomas is unknown. Whole-genome sequencing data generated as part of the Australian Melanoma Genome Project was supplemented with a detailed histopathological assessment with the melanomas then classified as UVR or non-UVR related, based on their mutation signatures. The clinicopathological characteristics of melanomas with mutation signatures for their subtype were compared...
January 9, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28067893/vemurafenib-and-trametinib-reduce-expression-of-ctgf-and-il-8-in-v600e-braf-melanoma-cells
#10
Mariusz L Hartman, Michal Rozanski, Marta Osrodek, Izabela Zalesna, Malgorzata Czyz
Clinical evidence has revealed that while RAS/RAF/MEK/ERK pathway is a crucial component of melanomagenesis, other signaling pathways can also contribute to the malignant growth and development of resistance to targeted therapies. We explored the response of (V600E)BRAF melanoma cells derived from surgical specimens and grown in stem cell medium to vemurafenib and trametinib, drugs targeting the activity of (V600E)BRAF and MEK1/2, respectively. Cell growth and apoptosis were monitored by real-time imaging system, immunophenotype and cell cycle by flow cytometry, gene expression by quantitative real-time PCR, immunoblotting and enzyme-linked immunosorbent assay...
January 9, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27991911/inhibition-of-infarction-induced-sympathetic-innervation-with-endothelin-receptor-antagonism-via-a-pi3k-gsk-3%C3%AE-dependent-pathway
#11
T-M Lee, Nen-Chung Chang, Shinn-Zong Lin
Although endothelin (ET)-1 has been shown to upregulate nerve growth factor (NGF) expression, the molecular mechanisms are largely unknown. Phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase (GSK)-3β signal has been implicated in the regulation of NGF. We investigated whether selective ET receptor blockers attenuated cardiac sympathetic reinnervation through restoring PI3K/Akt/GSK-3β activity. After ligation of the left anterior descending artery, male Wistar rats were randomized to either vehicle, atrasentan (an ETA receptor antagonist) or A-192621 (an ETB receptor antagonist) for 4 weeks...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27991910/establishment-and-characterization-of-bhd-f59rsvt-an-immortalized-cell-line-derived-from-a-renal-cell-carcinoma-in-a-patient-with-birt-hogg-dub%C3%A3-syndrome
#12
Mitsuko Furuya, Hisashi Hasumi, Masaya Baba, Reiko Tanaka, Yasuhiro Iribe, Takahiro Onishi, Yoji Nagashima, Yukio Nakatani, Yasuhiro Isono, Masahiro Yao
Hereditary renal cell carcinomas (RCCs) are life-threatening disorders not only for the patients but also for their relatives. Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN). The protein product, FLCN, functions as a tumor suppressor, and the affected patients have high risks of developing multiple RCCs. The carcinogenic mechanisms stemming from FLCN dysfunction have been investigated using rodent models and human RCC tissues. However, very limited information has been available about in vitro signaling of human renal cells with genetically mutant FLCN...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27991909/lymphatic-invasion-and-angiotropism-in-primary-cutaneous-melanoma
#13
Andrea P Moy, Lyn M Duncan, Stefan Kraft
Access of melanoma cells to the cutaneous vasculature either via lymphatic invasion or angiotropism is a proposed mechanism for metastasis. Lymphatic invasion is believed to be a mechanism by which melanoma cells can disseminate to regional lymph nodes and to distant sites and may be predictive of adverse outcomes. Although it can be detected on hematoxylin- and eosin-stained sections, sensitivity is markedly improved by immunohistochemistry for lymphatic endothelial cells. Multiple studies have reported a significant association between the presence of lymphatic invasion and sentinel lymph node metastasis and survival...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27991908/early-activated-hepatic-stellate-cell-derived-paracrine-molecules-modulate-acute-liver-injury-and-regeneration
#14
Wenju Chang, Lujun Song, Xiujuan Chang, Meiling Ji, Hongshan Wang, Xinyu Qin, Weixin Niu
The effects of paracrine action from early activated hepatic stellate cells (HSCs) on resident liver epithelium cells are not clear. Here, we investigated whether a systemic infusion of early activated HSC-derived paracrine factors (HSC-CM) would evoke an enhanced liver protective response in acetaminophen (APAP)-induced acute liver injury (ALI) in mice and explored the possible underlying mechanisms. The survival rate, liver injury, and liver regeneration were analyzed in mice with or without HSC-CM treatment in vivo...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27991907/immunomodulating-property-of-mapk-inhibitors-from-translational-knowledge-to-clinical-implementation
#15
Mario Mandalà, Francesco De Logu, Barbara Merelli, Romina Nassini, Daniela Massi
Treatment of metastatic melanoma was radically changed by the introduction of inhibitors of BRAF, an oncogene mutated in 40-50% of patients. Another area of advancement was the use of immunotherapy, and specifically, immune checkpoint inhibitors. There is compelling evidence that oncogenic BRAF, in addition to driving melanoma proliferation, differentiation and survival, induces T-cell suppression directly through the secretion of inhibitory cytokines or through membrane expression of co-inhibitory molecules such as the PD-1 ligands PD-L1 or PD-L2...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27991906/hepatic-stimulator-substance-inhibits-calcium-overflow-through-the-mitochondria-associated-membrane-compartment-during-nonalcoholic-steatohepatitis
#16
Fan Xiao, Jing Zhang, Can Zhang, Wei An
Nonalcoholic fatty liver disease is considered a disorder of the endoplasmic reticulum (ER) and mitochondria. Recent studies have shown that the ER and mitochondrial membranes overlap by 15-20%, a region referred to as the 'mitochondria-associated ER membrane' (MAM). Some proteins, including sarco/ER calcium ATPase (SERCA), are located in the MAM and have an important role in Ca(2+) signaling and homeostasis between the ER and the mitochondria. Our previous study showed that hepatic stimulator substance (HSS) inhibits the ER stress induced by reactive oxygen species, thus reducing mitochondrial damage...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27941757/characterization-of-histone-related-chemical-modifications-in-formalin-fixed-paraffin-embedded-and-fresh-frozen-human-pancreatic-cancer-xenografts-using-lc-ms-ms
#17
Monika Bauden, Theresa Kristl, Roland Andersson, György Marko-Varga, Daniel Ansari
Post-translational modifications (PTMs) of histones including acetylation, methylation, and ubiquitination are known to be involved in the epigenetic regulation of gene expression and thus can have an important role in tumorigenesis. A number of PTMs have been linked to pancreatic cancer and are frequently studied as potential targets for cancer therapy or diagnosis. The availability of biobank-stored, formalin-fixed, paraffin-embedded (FFPE) materials and advanced proteomic analytical tools make it possible to detect histone-related PTMs using predicted mass shifts caused by specific modification...
December 12, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27941756/h2s-inhibits-pulmonary-arterial-endothelial-cell-inflammation-in-rats-with-monocrotaline-induced-pulmonary-hypertension
#18
Shasha Feng, Siyao Chen, Wen Yu, Da Zhang, Chunyu Zhang, Chaoshu Tang, Junbao Du, Hongfang Jin
This study aimed to determine whether hydrogen sulfide (H2S) inhibits pulmonary arterial endothelial inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension and its possible mechanisms. Twenty-four male Wistar rats were divided randomly into control, MCT, and MCT+H2S treatment groups. Human pulmonary arterial endothelial cells (HPAEC) were cultured and divided into four groups: control, MCT, MCT+H2S, and H2S. Pulmonary artery pressure was determined using a right cardiac catheterization procedure 3 weeks after MCT administration...
December 12, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27941755/fibroblastic-foci-covered-with-alveolar-epithelia-exhibiting-epithelial-mesenchymal-transition-destroy-alveolar-septa-by-disrupting-blood-flow-in-idiopathic-pulmonary-fibrosis
#19
Miki Yamaguchi, Sachie Hirai, Yusuke Tanaka, Toshiyuki Sumi, Masahiro Miyajima, Taijiro Mishina, Gen Yamada, Mitsuo Otsuka, Tadashi Hasegawa, Takashi Kojima, Toshiro Niki, Atsushi Watanabe, Hiroki Takahashi, Yuji Sakuma
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown cause. IPF has a distinct histopathological pattern of usual interstitial pneumonia in which fibroblastic foci (FF) represent the leading edge of fibrotic destruction of the lung. Currently there are three major hypotheses for how FF are generated: (1) from resident fibroblasts, (2) from bone marrow-derived progenitors of fibroblasts, and (3) from alveolar epithelial cells that have undergone epithelial-mesenchymal transition (EMT)...
December 12, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27918557/automated-evaluation-of-liver-fibrosis-in-thioacetamide-carbon-tetrachloride-and-bile-duct-ligation-rodent-models-using-second-harmonic-generation-two-photon-excited-fluorescence-microscopy
#20
Feng Liu, Long Chen, Hui-Ying Rao, Xiao Teng, Ya-Yun Ren, Yan-Qiang Lu, Wei Zhang, Nan Wu, Fang-Fang Liu, Lai Wei
Animal models provide a useful platform for developing and testing new drugs to treat liver fibrosis. Accordingly, we developed a novel automated system to evaluate liver fibrosis in rodent models. This system uses second-harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy to assess a total of four mouse and rat models, using chemical treatment with either thioacetamide (TAA) or carbon tetrachloride (CCl4), and a surgical method, bile duct ligation (BDL). The results obtained by the new technique were compared with that using Ishak fibrosis scores and two currently used quantitative methods for determining liver fibrosis: the collagen proportionate area (CPA) and measurement of hydroxyproline (HYP) content...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
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