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https://www.readbyqxmd.com/read/28052321/canonical-hedgehog-signaling-regulates-hepatic-stellate-cell-mediated-angiogenesis-in-liver-fibrosis
#1
Feng Zhang, Meng Hao, Huanhuan Jin, Zhen Yao, Naqi Lian, Li Wu, Jiangjuan Shao, Anping Chen, Shizhong Zheng
BACKGROUND AND PURPOSE: Hepatic stellate cells (HSCs) are liver-specific pericytes regulating angiogenesis during liver fibrosis. We aimed to elucidate the mechanisms by which hedgehog signaling regulated HSC angiogenic properties and to validate the therapeutic implications. EXPERIMENTAL APPROACH: Rats and mice were intoxicated with carbon tetrachloride for in vivo evaluation of hepatic angiogenesis and fibrotic injury. Diversified molecular approaches including real-time PCR, Western blot, luciferase reporter assay, chromatin immunoprecipitation, electrophoretic mobility shift assay, and co-immunoprecipitation were used to investigate the underlying mechanisms in vitro...
January 4, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28031756/does-the-mthfr-a1298c-polymorphism-modulate-the-cardiorespiratory-response-to-training
#2
Paweł Cięszczyk, Aleksandra Zarębska, Zbigniew Jastrzębski, Michał Sawczyn, Izabela Kozakiewicz-Drobnik, Agata Leońska-Duniec, Mariusz Kaczmarczyk, Agnieszka Maciejewska-Skrendo, Piotr Żmijewski, Grzegorz Trybek, Wojciech Smółka, Jan Pilch, Katarzyna Leźnicka, Ewelina Lulińska-Kuklik, Marek Sawczuk, Myosotis Massidda
The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphic variant is a candidate to explain the individual differences in trainability and response to exercise training. Therefore, the aim of the study was to verify whether the A1298C polymorphism influenced the aerobic and anaerobic performance as well as body and mass composition in young Polish women following low-high impact aerobic exercise training. Two hundred and one women aged 21 ± 1 years (range 19-24) were included in the study...
December 1, 2016: Journal of Human Kinetics
https://www.readbyqxmd.com/read/28019670/smoothened-antagonists-reverse-homogentisic-acid-induced-alterations-of-hedgehog-signalling-and-primary-cilium-length-in-alkaptonuria
#3
Silvia Gambassi, Michela Geminiani, Stephen D Thorpe, Giulia Bernardini, Lia Millucci, Daniela Braconi, Maurizio Orlandini, Clare L Thompson, Elena Petricci, Fabrizio Manetti, Maurizio Taddei, Martin M Knight, Annalisa Santucci
Alkaptonuria (AKU) is an ultra-rare genetic disease, in which the accumulation of a toxic metabolite, homogentisic acid (HGA) leads to the systemic development of ochronotic aggregates. These aggregates cause severe complications mainly at the level of joints with extensive degradation of the articular cartilage. Primary cilia have been demonstrated to play an essential role in development and the maintenance of articular cartilage homeostasis, through their involvement in mechanosignalling and Hedgehog signalling pathways...
December 26, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28018716/machine-learning-based-detection-of-age-related-macular-degeneration-amd-and-diabetic-macular-edema-dme-from-optical-coherence-tomography-oct-images
#4
Yu Wang, Yaonan Zhang, Zhaomin Yao, Ruixue Zhao, Fengfeng Zhou
Non-lethal macular diseases greatly impact patients' life quality, and will cause vision loss at the late stages. Visual inspection of the optical coherence tomography (OCT) images by the experienced clinicians is the main diagnosis technique. We proposed a computer-aided diagnosis (CAD) model to discriminate age-related macular degeneration (AMD), diabetic macular edema (DME) and healthy macula. The linear configuration pattern (LCP) based features of the OCT images were screened by the Correlation-based Feature Subset (CFS) selection algorithm...
December 1, 2016: Biomedical Optics Express
https://www.readbyqxmd.com/read/28009972/inhibition-of-the-hedgehog-pathway-leads-to-antifibrotic-effects-in-dermal-fibrosis
#5
Hua-Li Cao, Jiong Zhou, Xi-Bei Chen, Lilla Landeck, Jian-Qiang Yang, Jia-Qi Chen, Wei Li, Sui-Qing Cai, Min Zheng, Xiao-Yong Man
Dermal fibrosis is characterized by the activation of the matrix-producing 'positive' myofibroblasts, and the relentless production and deposition of extracellular matrix. The hedgehog pathway has recently been demonstrated to work in a pro-fibrotic manner in systemic sclerosis (SSc). A negative regulator of the hedgehog pathway (Hh), the suppressor of fused (Sufu), was shown to be involved in the activation of fibrotic diseases. However, the exact role of Sufu in fibrosis has not been investigated so far. In our study, we aimed to define the role of sufu in the process of fibrosis using dermal fibroblasts of healthy donors that were cultured in vitro...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27983916/silencing-of-a-kinase-anchor-protein-4-akap4-inhibits-proliferation-and-progression-of-thyroid-cancer
#6
Jiakai Han, Wei Gao, Dongyue Su, Yang Liu
A-kinase anchor protein 4 (AKAP4), a member of the A-kinase anchor proteins, plays a role in tumor development and progression. However, its expression pattern and function in human thyroid cancer remain obscure. Here, we examined AKAP4 expression in thyroid cancer cell lines. Additionally, the effects of AKAP4 on the proliferation and metastasis of thyroid cancer cells was examined. Finally, we explored the molecular mechanism by which AKAP4 mediates the metastatic potential of thyroid cancer cells. Our results revealed that the transcript and protein levels of AKAP4 were significantly up-regulated in thyroid cancer cell lines...
November 8, 2016: Oncology Research
https://www.readbyqxmd.com/read/27965463/ameloblastoma-rna-profiling-uncovers-a-distinct-non-coding-rna-signature
#7
Haleh Davanian, Anangi Balasiddaiah, Robert Heymann, Magnus Sundström, Poppy Redenström, Mikael Silfverberg, David Brodin, Matti Sällberg, Sven Lindskog, Carina Kruger Weiner, Margaret Chen
Ameloblastoma of the jaws remains the top difficult to treat odontogenic tumour and has a high recurrence rate. New evidence suggests that non-coding RNAs (ncRNAs) play a critical role in tumourgenesis and prognosis of cancer. However, ameloblastoma ncRNA expression data is lacking. Here we present the first report of ameloblastoma ncRNA signatures. A total of 95 ameloblastoma cases and a global array transcriptome technology covering > 285.000 full-length transcripts were used in this two-step analysis...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27959416/microrna-1271-inhibits-proliferation-and-promotes-apoptosis-of-multiple-myeloma-cells-through-inhibiting-smoothened-mediated-hedgehog-signaling-pathway
#8
Zhengwei Xu, Chen Huang, Dingjun Hao
MicroRNAs (miRNAs) have emerged as important regulators in multiple myeloma (MM). miR-1271 is a tumor suppressor in many cancer types. However, the biological role of miR-1271 in MM remains unclear. In the present study, we elucidated the biological role of miR-1271 in MM. Results showed that miR-1271 was significantly decreased in primary MM cells from MM patients and MM cell lines. Overexpression of miR-1271 inhibited proliferation and promoted apoptosis of MM cells. Conversely, suppression of miR-1271 showed the opposite effect...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27942391/metastatic-basal-cell-carcinoma-with-amplification-of-pd-l1-exceptional-response-to-anti-pd1-therapy
#9
Sadakatsu Ikeda, Aaron M Goodman, Philip R Cohen, Taylor J Jensen, Christopher K Ellison, Garrett Frampton, Vincent Miller, Sandip P Patel, Razelle Kurzrock
Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA)...
2016: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/27941997/primary-cilia-negatively-regulate-melanogenesis-in-melanocytes-and-pigmentation-in-a-human-skin-model
#10
Hyunjung Choi, Ji Hyun Shin, Eun Sung Kim, So Jung Park, Il-Hong Bae, Yoon Kyung Jo, In Young Jeong, Hyoung-June Kim, Youngjin Lee, Hea Chul Park, Hong Bae Jeon, Ki Woo Kim, Tae Ryong Lee, Dong-Hyung Cho
The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown...
2016: PloS One
https://www.readbyqxmd.com/read/27928965/targeting-the-hedgehog-pathway-for-locally-advanced-and-metastatic-basal-cell-carcinoma
#11
Vivian T Yin, Bita Esmaeli
Basal cell caricnoma (BCC), the most common periocular magliancy, is treated with complete surgical excision. However, in patients not amenable to surgery or when surgical resection means loss of vital organs or disfiguring procedures due to locally advanced or metastatic disease, targeting the hedgehog pathway offers anovel treatment approach for such patients. Mutation in PTCH1 and SMO has been identified in patients with basal cell nevoid syndrome as well as in patients with sporadic BCC. Inhibition of SMO by vismodegib or sonidegib, the two sonic hedgehog inhibitor drugs approved by the Food and Drug Administration in the United States, has shown overall response rate for locally advanced and metastatic BCC around 50%...
December 7, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27917272/the-hedgehog-gli-1-signaling-pathways-is-involved-in-the-inhibitory-effect-of-resveratrol-on-human-colorectal-cancer-hct116-cells
#12
Zhou Du, Feng Zhou, Zengrong Jia, Beishi Zheng, Shaoliang Han, Jun Cheng, Guanbao Zhu, Ping Huang
OBJECTIVES: The study aimed to investigate the effects of resveratrol on colorectal cancer HCT116 cells, including cell viability, apoptosis, and migration, and the partial mechanisms focused on hedgehog/gli-1 signaling pathways. MATERIALS AND METHODS: We chose the appropriate time and concentration of recombinant human Sonic hedgehog (Shh) stimulation by cell viability. The proportion of cell apoptosis was detected by flow cytometry; HCT116 cell migration was measured by scratch test; the expression of Ptch, Smo, and Gli-1 was measured by Western blot analysis...
November 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27903983/dyrk1b-blocks-canonical-and-promotes-non-canonical-hedgehog-signaling-through-activation-of-the-mtor-akt-pathway
#13
Rajeev Singh, Pavan Kumar Dhanyamraju, Matthias Lauth
Hedgehog (Hh) signaling plays important roles in embryonic development and in tumor formation. Apart from the well-established stimulation of the GLI family of transcription factors, Hh ligands promote the phosphorylation and activation of mTOR and AKT kinases, yet the molecular mechanism underlying these processes are unknown. Here, we identify the DYRK1B kinase as a mediator between Hh signaling and mTOR/AKT activation. In fibroblasts, Hh signaling induces DYRK1B protein expression, resulting in activation of the mTOR/AKT kinase signaling arm...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899820/inhibition-of-hedgehog-dependent-tumors-and-cancer-stem-cells-by-a-newly-identified-naturally-occurring-chemotype
#14
Paola Infante, Romina Alfonsi, Cinzia Ingallina, Deborah Quaglio, Francesca Ghirga, Ilaria D'Acquarica, Flavia Bernardi, Laura Di Magno, Gianluca Canettieri, Isabella Screpanti, Alberto Gulino, Bruno Botta, Mattia Mori, Lucia Di Marcotullio
Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range of cancers. Indeed, aberrant activation of the Hh pathway occurring either by ligand-dependent or -independent mechanisms is a key driver in tumorigenesis. The smoothened (Smo) receptor is one of the main upstream transducers of the Hh signaling and is a validated target for the development of anticancer compounds, as underlined by the FDA-approved Smo antagonist Vismodegib (GDC-0449/Erivedge) for the treatment of basal cell carcinoma...
September 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27897284/ytterbium-erbium-ion-doped-strontium-molybdate-srmoo4-synthesis-characterization-photophysical-properties-and-application-in-solar-cells
#15
Weifu Sun, Zihan Chen, Junli Zhou, Dongyu Li, Zhen Huang, Xiao Jin, Qin Zhang, Feng Li, Qinghua Li
In this work, ytterbium-erbium co-doped strontium molybdate (SrMoO4, SMO) nanophosphors (NPs), denoted as SMO:Yb/Er, have been successfully prepared. These NPs were then incorporated into TiO2 acceptor films in hybrid solar cells to enhance light harvesting by virtue of an up-conversion process where low energy photons can be converted into high energy photons through multi-photon processes. The results showed that the SMO:Yb/Er single crystal NPs are capable of turning near infrared photons into visible ones that can be easily captured by poly(thieno[3,4-b]-thiophene/benzodithiophene) (PTB7)...
December 7, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27885953/targeted-sequencing-of-smo-and-akt1-in-anterior-skull-base-meningiomas
#16
Matthew R Strickland, Corey M Gill, Naema Nayyar, Megan R D'Andrea, Christian Thiede, Tareq A Juratli, Gabriele Schackert, Darrell R Borger, Sandro Santagata, Matthew P Frosch, Daniel P Cahill, Priscilla K Brastianos, Fred G Barker
OBJECTIVE Meningiomas located in the skull base are surgically challenging. Recent genomic research has identified oncogenic SMO and AKT1 mutations in a small subset of meningiomas. METHODS The authors performed targeted sequencing in a large cohort of patients with anterior skull base meningiomas (n = 62) to better define the frequency of SMO and AKT1 mutations in these tumors. RESULTS The authors found SMO mutations in 7 of 62 (11%) and AKT1 mutations in 12 of 62 (19%) of their cohort. Of the 7 meningiomas with SMO mutations, 6 (86%) occurred in the olfactory groove...
November 25, 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27877222/hedgehog-signaling-non-canonical-activated-by-pro-inflammatory-cytokines-in-pancreatic-ductal-adenocarcinoma
#17
Yuqiong Wang, Gang Jin, Quanjiang Li, Zhiping Wang, Weimin Hu, Ping Li, Shude Li, Hongyu Wu, Xiangyu Kong, Jun Gao, Zhaoshen Li
Hedgehog(HH) pathway is found to be activated through a manner of canonical, or the non-canonical HH pathways. Distinct hyperplasia stroma around tumor cells is supposed to express pro-inflammatory cytokines abundantly, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), etc. in pancreatic ductal adenocarcinoma (PDAC) tissues. In this study we observed the effects of TNF-α and IL-1β on HH pathway activation in PDAC cells, and explored their activation manners. Our results showed that pro-inflammatory cytokines, TNF-α and IL-1β, could up-regulate the expression of GLI1 gene, increase its nuclear protein expression and promote malignant cell behaviors including migration, invasion, epithelial-mesenchymal transition (EMT) and drug resistance as well...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27875522/hedgehog-inhibition-enhances-efficacy-of-radiation-and-cisplatin-in-orthotopic-cervical-cancer-xenografts
#18
Naz Chaudary, Melania Pintilie, David Hedley, Richard P Hill, Michael Milosevic, Helen Mackay
BACKGROUND: The Hedgehog (Hh) pathway is upregulated in cervical cancer and associated with poor outcome. We explored the effects of Hh pathway inhibition in combination with RTCT in a patient derived orthotopic cervical cancer xenograft model (OCICx). METHODS: 5E1, a monoclonal antibody for SHH, or Sonidegib (LDE225), a clinical SMO inhibitor (Novartis) were added to RTCT. We investigated tumour growth delay, metastasis and GI toxicity using orthotopic cervical cancer xenografts models...
January 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/27835885/galectin-1-induces-invasion-and-the-epithelial-mesenchymal-transition-in-human-gastric-cancer-cells-via-non-canonical-activation-of-the-hedgehog-signaling-pathway
#19
Yang Chong, Dong Tang, Jun Gao, Xuetong Jiang, Chuanqi Xu, Qingquan Xiong, Yuqin Huang, Jie Wang, Huaicheng Zhou, Youquan Shi, Daorong Wang
Galectin-1 (Gal-1) has been reported to be an independent prognostic indicator of poor survival in gastric cancer and overexpression of Gal-1 enhances the invasiveness of gastric cancer cells. However, the downstream mechanisms by which Gal-1 promotes invasion remains unclear. Moreover, the function of Gal-1 in the epithelial-mesenchymal transition (EMT) in gastric cancer has not yet been elucidated. In this study, we observed Gal-1 expression was upregulated and positively associated with metastasis and EMT markers in 162 human gastric cancer tissue specimens...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27825128/activation-of-the-basal-cell-carcinoma-pathway-in-a-patient-with-cns-hgnet-bcor-diagnosis-consequences-for-personalized-targeted-therapy
#20
Claudia Paret, Johanna Theruvath, Alexandra Russo, Bettina Kron, Khalifa El Malki, Nadine Lehmann, Arthur Wingerter, Marie A Neu, Aslihan Gerhold-Ay, Wolfgang Wagner, Clemens Sommer, Torsten Pietsch, Larissa Seidmann, Jörg Faber
High grade neuroepithelial tumor of the central nervous system with BCOR alteration (CNS HGNET-BCOR) is a recently described new tumor entity with a dismal prognosis. The objective of this study was to identify and validate pathways deregulated in CNS HGNET-BCOR as basis for targeted therapy approaches.We characterized the BCOR alteration in a pediatric patient with CNS HGNET-BCOR diagnosis by Sanger sequencing and demonstrated an elevated BCOR expression by qRT-PCR and western blot. By whole transcriptome sequencing and Ingenuity Pathway Analysis, we identified the activation of the Sonic Hedgehog (SHH) and of the WNT signaling pathway in two different regions of the primary tumor and of one inoculation metastasis compared to normal brain...
November 4, 2016: Oncotarget
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