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Laboratory Investigation; a Journal of Technical Methods and Pathology

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https://www.readbyqxmd.com/read/28218743/vitamin-d-signaling-and-melanoma-role-of-vitamin-d-and-its-receptors-in-melanoma-progression-and-management
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28218740/maresin1-stimulates-alveolar-fluid-clearance-through-the-alveolar-epithelial-sodium-channel-na-k-atpase-via-the-alx-pi3k-nedd4-2-pathway
#4
Jun-Li Zhang, Xiao-Jun Zhuo, Jing Lin, Ling-Chun Luo, Wei-Yang Ying, Xiang Xie, Hua-Wei Zhang, Jing-Xiang Yang, Dan Li, Fang Gao Smith, Sheng-Wei Jin
Maresin1 (MaR1) is a new docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. In this study, we sought to investigate the effect and underlining mechanisms of MaR1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. MaR1 was injected intravenously or administered by instillation (200 ng/kg) 8 h after LPS (14 mg/kg) administration and AFC was measured in live rats. In primary rat alveolar type II epithelial cells, MaR1 (100 nM) was added to the culture medium with lipopolysaccharide for 6 h...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28218739/suppression-of-islet-homeostasis-protein-thwarts-diabetes-mellitus-progression
#5
Seh-Hoon Oh, Marda L Jorgensen, Clive H Wasserfall, Altin Gjymishka, Bryon E Petersen
During progression to type 1 diabetes, insulin-producing β-cells are lost through an autoimmune attack resulting in unrestrained glucagon expression and secretion, activation of glycogenolysis, and escalating hyperglycemia. We recently identified a protein, designated islet homeostasis protein (IHoP), which specifically co-localizes within glucagon-positive α-cells and is overexpressed in the islets of both post-onset non-obese diabetic (NOD) mice and type 1 diabetes patients. Here we report that in the αTC1...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28218738/adipogenic-niches-for-melanoma-cell-colonization-and-growth-in-bone-marrow
#6
Juan Wang, Guang-Liang Chen, Shan Cao, Ming-Chun Zhao, Yong-Qing Liu, Xiao-Xiang Chen, Cheng Qian
Bone marrow (BM) adipocytes are abundant in BM and may be involved in the process of bone metastasis. However, their behaviors in metastatic BM niches during bone metastasis have not been fully explored. In this study, intracardiac transplantation of B16-F10 melanoma cells into immunocompetent C57BL/6 mice was performed. Tibial marrow sections were stained with hematoxylin and eosin, Masson's trichrome, tartrate-resistant acid phosphatase, and fatty acid-binding protein 4 (FABP4) and analyzed using a histomorphometric system...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28194034/high-pressure-carbon-monoxide-preserves-rat-kidney-grafts-from-apoptosis-and-inflammation
#7
Toyofumi Abe, Koji Yazawa, Masayuki Fujino, Ryoichi Imamura, Naoyuki Hatayama, Yoichi Kakuta, Koichi Tsutahara, Masayoshi Okumi, Naotsugu Ichimaru, Jun-Ya Kaimori, Yoshitaka Isaka, Kunihiro Seki, Shiro Takahara, Xiao-Kang Li, Norio Nonomura
Renal ischemia-reperfusion (I/R) injury is unavoidable in kidney transplantation (KTx) and frequently influences both short- and long-term allograft survival. Carbon monoxide (CO) has attracted attention as a medical gas with anti-inflammatory and anti-apoptotic effects. We investigated a new strategy for organ preservation using ex vivo application of high-pressure CO in an experimental rat KTx model. We preserved kidney grafts using a high-pressure chamber filled with mixed gases composed of CO and O2. We found that cold I/R injury resulted in progressive deterioration of renal graft function in University of Wisconsin solution, whereas CO significantly improved renal function...
February 13, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28165470/sodium-chloride-promotes-tissue-inflammation-via-osmotic-stimuli-in-subtotal-nephrectomized-mice
#8
Fumiko Sakata, Yasuhiko Ito, Masashi Mizuno, Akiho Sawai, Yasuhiro Suzuki, Takako Tomita, Mitsuhiro Tawada, Akio Tanaka, Akiyoshi Hirayama, Akihiro Sagara, Takashi Wada, Shoichi Maruyama, Tomoyoshi Soga, Seiichi Matsuo, Enyu Imai, Yoshifumi Takei
Chronic inflammation, which is often associated with high all-cause and cardiovascular mortality, is prevalent in patients with renal failure; however, the precise mechanisms remain unclear. High-salt intake was reported to induce lymphangiogenesis and autoimmune diseases via osmotic stimuli with accumulation of sodium or chloride. In addition, sodium was recently reported to be stored in the extremities of dialysis patients. We studied the effects and mechanisms of high salt loading on tissue and systemic inflammation in subtotal-nephrectomized mice (5/6Nx) and in cultured cells...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28165469/notch3-signaling-mediated-melanoma-endothelial-crosstalk-regulates-melanoma-stem-like-cell-homeostasis-and-niche-morphogenesis
#9
Mei-Yu Hsu, Moon Hee Yang, Caroline I Schnegg, Soonyean Hwang, Byungwoo Ryu, Rhoda M Alani
Melanoma is among the most virulent cancers, owing to its propensity to metastasize and its resistance to current therapies. The treatment failure is largely attributed to tumor heterogeneity, particularly subpopulations possessing stem cell-like properties, ie, melanoma stem-like cells (MSLCs). Evidence indicates that the MSLC phenotype is malleable and may be acquired by non-MSLCs through phenotypic switching upon appropriate stimuli, the so-called 'dynamic stemness'. Since the phenotypic characteristics and functional integrity of MSLCs depend on their vascular niche, using a two-dimensional (2D) melanoma-endothelium co-culture model, where the MSLC niche is recapitulated in vitro, we identified Notch3 signaling pathway as a micro-environmental cue governing MSLC phenotypic plasticity via pathway-specific gene expression arrays...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28165468/thy-1-interaction-with-fas-in-lipid-rafts-regulates-fibroblast-apoptosis-and-lung-injury-resolution
#10
Xiaoqiu Liu, Simon S Wong, Carmen A Taype, Jeeyeon Kim, Tzu-Pin Shentu, Celia R Espinoza, J Cameron Finley, John E Bradley, Brian P Head, Hemal H Patel, Emma J Mah, James S Hagood
Thy-1-negative lung fibroblasts are resistant to apoptosis. The mechanisms governing this process and its relevance to fibrotic remodeling remain poorly understood. By using either sorted or transfected lung fibroblasts, we found that Thy-1 expression is associated with downregulation of anti-apoptotic molecules Bcl-2 and Bcl-xL, as well as increased levels of cleaved caspase-9. Addition of rhFasL and staurosporine, well-known apoptosis inducers, caused significantly increased cleaved caspase-3, -8, and PARP in Thy-1-transfected cells...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28165467/apx-115-a-first-in-class-pan-nadph-oxidase-nox-inhibitor-protects-db-db-mice-from-renal-injury
#11
Jin Joo Cha, Hye Sook Min, Ki Tae Kim, Jung Eun Kim, Jung Yeon Ghee, Hyun Wook Kim, Ji Eun Lee, Jee Young Han, Gayoung Lee, Hun Joo Ha, Yun Soo Bae, Sae Rom Lee, Sung Hwan Moon, Sung Chan Lee, Ganghyun Kim, Young Sun Kang, Dae Ryong Cha
Recent studies have suggested that renal Nox is important in the progression of diabetic nephropathy. Therefore, we investigated the effect of a novel pan-NOX-inhibitor, APX-115, on diabetic nephropathy in type 2 diabetic mice. Eight- week-old db/m and db/db mice were treated with APX-115 for 12 weeks. APX-115 was administered by oral gavage at a dose of 60 mg/kg per day. To compare the effects of APX-115 with a dual Nox1/Nox4 inhibitor, db/db mice were treated with GKT137831 according to the same protocol...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28165466/tauroursodeoxycholic-acid-protects-bile-acid-homeostasis-under-inflammatory-conditions-and-dampens-crohn-s-disease-like-ileitis
#12
Lien Van den Bossche, Daniel Borsboom, Sarah Devriese, Sophie Van Welden, Tom Holvoet, Lindsey Devisscher, Pieter Hindryckx, Martine De Vos, Debby Laukens
Bile acids regulate the expression of intestinal bile acid transporters and are natural ligands for nuclear receptors controlling inflammation. Accumulating evidence suggests that signaling through these receptors is impaired in inflammatory bowel disease. We investigated whether tauroursodeoxycholic acid (TUDCA), a secondary bile acid with cytoprotective properties, regulates ileal nuclear receptor and bile acid transporter expression and assessed its therapeutic potential in an experimental model of Crohn's disease (CD)...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28134916/rescue-of-retinal-morphology-and-function-in-a-humanized-mouse-at-the-mouse-retinol-binding-protein-locus
#13
Li Liu, Tomohiro Suzuki, Jingling Shen, Shigeharu Wakana, Kimi Araki, Ken-Ichi Yamamura, Lei Lei, Zhenghua Li
Retinol-binding protein RBP4 is the specific carrier for retinol in the blood. We previously produced a Rbp4-deficient (Rbp4(-/-)) mouse that showed electroretinogram (ERG) abnormalities, accompanied by histological and electron-microscopic changes such as fewer synapses in the inner plexiform layer in the central retina. To address whether human RBP4 gene expression can rescue the phenotypes observed in Rbp4(-/-) mice, we produced a humanized (Rbp4(hRBP4orf/ hRBP4orf)) mouse with a human RBP4 open reading frame in the mouse Rbp4 locus using a Cre-mutant lox recombination system...
January 30, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28112758/regeneration-of-thyroid-follicles-from-primordial-cells-in-a-murine-thyroidectomized-model
#14
Junguee Lee, Shinae Yi, Joon Young Chang, Yea Eun Kang, Hyun Jung Kim, Ki Cheol Park, Keum-Jin Yang, Hae Joung Sul, Jong Ok Kim, Hyon-Seung Yi, Xuguang Zhu, Sheue-Yann Cheng, Minho Shong
The functional unit of the thyroid gland, the thyroid follicle, dynamically responds to various stimuli to maintain thyroid hormone homeostasis. However, thyroid follicles in the adult human thyroid gland have a very limited regenerative capacity following partial resection of the thyroid gland. To gain insight into follicle regeneration in the adult thyroid gland, we observed the regeneration processes of murine thyroid follicles after partial resection of the lower third of the thyroid gland in 10-week-old male C57BL/6 mice...
January 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28112757/reversal-of-maladaptive-fibrosis-and-compromised-ventricular-function-in-the-pressure-overloaded-heart-by-a-caveolin-1-surrogate-peptide
#15
Dorea Pleasant-Jenkins, Charles Reese, Panneerselvem Chinnakkannu, Harinath Kasiganesan, Elena Tourkina, Stanley Hoffman, Dhandapani Kuppuswamy
Chronic ventricular pressure overload (PO) results in congestive heart failure (CHF) in which myocardial fibrosis develops in concert with ventricular dysfunction. Caveolin-1 is important in fibrosis in various tissues due to its decreased expression in fibroblasts and monocytes. The profibrotic effects of low caveolin-1 can be blocked with the caveolin-1 scaffolding domain peptide (CSD, a caveolin-1 surrogate) using both mouse models and human cells. We have studied the beneficial effects of CSD on mice in which PO was induced by trans-aortic constriction (TAC)...
January 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28112756/long-noncoding-rna-ftx-is-upregulated-in-gliomas-and-promotes-proliferation-and-invasion-of-glioma-cells-by-negatively-regulating-mir-342-3p
#16
Weiguang Zhang, Yunke Bi, Jianhua Li, Fei Peng, Hui Li, Chenguang Li, Laizang Wang, Fubin Ren, Chen Xie, Pengwei Wang, Weiwei Liang, Zhi Wang, Dan Zhu
Gliomas remain a major public health challenge, posing a high risk for brain tumor-related morbidity and mortality. However, the mechanisms that drive the development of gliomas remain largely unknown. Emerging evidence has shown that long noncoding RNAs are key factors in glioma pathogenesis. qRT-PCR analysis was used to assess the expression of FTX and miR-342-3p in the different stages of gliomas in tissues. Bioinformatics tool DIANA and TargetSCan were used to predict the targets of FTX and miR-342-3p, respectively...
January 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28112755/larger-core-size-has-superior-technical-and-analytical-accuracy-in-bladder-tissue-microarray
#17
Adel Rh Eskaros, Shanna A Arnold Egloff, Kelli L Boyd, Joyce E Richardson, M Eric Hyndman, Andries Zijlstra
The construction of tissue microarrays (TMAs) with cores from a large number of paraffin-embedded tissues (donors) into a single paraffin block (recipient) is an effective method of analyzing samples from many patient specimens simultaneously. For the TMA to be successful, the cores within it must capture the correct histologic areas from the donor blocks (technical accuracy) and maintain concordance with the tissue of origin (analytical accuracy). This can be particularly challenging for tissues with small histological features such as small islands of carcinoma in situ (CIS), thin layers of normal urothelial lining of the bladder, or cancers that exhibit intratumor heterogeneity...
January 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28112754/gdm-alters-paracrine-regulation-of-feto-placental-angiogenesis-via-the-trophoblast
#18
Jelena Loegl, Erika Nussbaumer, Silvija Cvitic, Berthold Huppertz, Gernot Desoye, Ursula Hiden
Feto-placental angiogenesis and vascular development are tightly regulated by pro- and anti-angiogenic factors. Villous trophoblast may be a major source of these factors. It forms the classical placental barrier between mother and fetus, and is thus exposed to maternal influences as well. Metabolic and hormonal derangements in gestational diabetes mellitus (GDM) affect feto-placental angiogenesis and vascular growth. Here we hypothesized that GDM alters the trophoblast secretome, which will modulate the paracrine regulation of feto-placental angiogenesis...
January 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28092366/malignant-melanoma-of-sun-protected-sites-a-review-of-clinical-histological-and-molecular-features
#19
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
#20
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
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