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https://www.readbyqxmd.com/read/28550140/erk1b-a-46-kda-erk-isoform-that-is-differentially-regulated-by-mek
#1
Yuval Yung, Zhong Yao, Tamar Hanoch, Rony Seger
No abstract text is available yet for this article.
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28550040/kras-g12d-expression-in-lung-resident-myeloid-cells-promotes-pulmonary-lch-like-neoplasm-sensitive-to-statin-treatment
#2
Tamihiro Kamata, Susan Giblett, Catrin Pritchard
Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm associated with somatic mutations in the genes involved in the RAF/MEK/ERK signaling pathway. Recently, oncogenic mutations in NRAS/KRAS, upstream regulators of the RAF/MEK/ERK pathway, have been reported in pulmonary, but not in non-pulmonary, LCH cases, suggesting organ-specific contribution of oncogenic RAS to LCH pathogenesis. Using a mouse model expressing KRAS(G12D) in the lung by nasal delivery of adenoviral Cre, here we show that KRAS(G12D) expression in lung-resident myeloid cells induces pulmonary LCH-like neoplasms comprised of pathogenic CD11c(high)F4/80+CD207+ cells...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28546426/guanine-nucleotide-exchange-factor-epac2-dependent-activation-of-the-gtp-binding-protein-rap2a-mediates-camp-dependent-growth-arrest-in-neuroendocrine-cells
#3
Andrew C Emery, Wenqin Xu, Maribeth V Eiden, Lee E Eiden
First messenger-dependent activation of MAPKs in neuronal and endocrine cells is critical for cell differentiation and function and requires guanine nucleotide exchange factor (GEF)- mediated activation of downstream Ras-family small GTPases, which ultimately lead to ERK, JNK, and p38 phosphorylation. Because there are numerous GEFs and also a host of Ras-family small GTPases, it is important to know which specific GEF-small GTPase dyad functions in a given cellular process. Here, we investigated the upstream activators and downstream effectors of signaling via the GEF Epac2 in the neuroendocrine NS-1 cell line...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28545687/synergistic-effect-of-mek-inhibitor-and-metformin-combination-in-low-grade-serous-ovarian-cancer
#4
Ismail Mert, Jasdeep Chhina, Ghassan Allo, Jing Dai, Shelly Seward, Mark S Carey, Marta Llaurado, Shailendra Giri, Ramandeep Rattan, Adnan R Munkarah
OBJECTIVE: Low-grade serous ovarian cancer (LGSOC) constitutes 5-8% of epithelial ovarian cancers and is refractory to chemotherapy. We and others have shown metformin to cause significant growth inhibition in high-grade ovarian cancer both in vitro and in vivo. Here, we aimed to analyze if metformin was effective in inhibiting proliferation of LGSOC alone and in combination with MEK inhibitor. METHODS: Three LGSOC lines (VOA1056, VOA1312 and VOA5646) were treated with metformin, trametinib or 2-deoxyglucose (2DG) alone or in combination with metformin...
May 22, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28545562/the-inhibition-of-fgf-receptor-1-activity-mediates-sorafenib-antiproliferative-effects-in-human-malignant-pleural-mesothelioma-tumor-initiating-cells
#5
Alessandra Pattarozzi, Elisa Carra, Roberto E Favoni, Roberto Würth, Daniela Marubbi, Rosa Angela Filiberti, Luciano Mutti, Tullio Florio, Federica Barbieri, Antonio Daga
BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer, characterized by rapid progression and high mortality. Persistence of tumor-initiating cells (TICs, or cancer stem cells) after cytotoxic drug treatment is responsible for tumor relapse, and represents one of the main reasons for the poor prognosis of mesothelioma. In fact, identification of the molecules affecting TIC viability is still a significant challenge. METHODS: TIC-enriched cultures were obtained from 10 human malignant pleural mesotheliomas and cultured in vitro...
May 25, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28545088/transcriptional-activation-of-hif-1-by-a-ros-erk-axis-underlies-the-resistance-to-photodynamic-therapy
#6
María Julia Lamberti, María Florencia Pansa, Renzo Emanuel Vera, Martín Ernesto Fernández-Zapico, Natalia Belén Rumie Vittar, Viviana Alicia Rivarola
Photodynamic therapy (PDT), a promising treatment option for cancer, involves the activation of a photosensitizer (PS) by local irradiation with visible light. Excitation of the PS leads to a series of photochemical reactions and consequently the local generation of harmful reactive oxygen species (ROS) causing limited or none systemic defects. However, the development of resistance to this promising therapy has slowed down its translation into the clinical practice. Thus, there is an increase need in understanding of the molecular mechanism underlying resistance to PDT...
2017: PloS One
https://www.readbyqxmd.com/read/28544403/serine-protease-inhibitor-kazal-type-1-spink1-downregulates-e-cadherin-and-induces-emt-of-hepatoma-cells-to-promote-hepatocellular-carcinoma-metastasis-via-the-mek-erk-signaling-pathway
#7
Ying Hai-Yan, Gong Chao-Jie, Feng Yi, Jing Da-Dao, Lun-Gen Lu
OBJECTIVE: To investigate serine protease inhibitor Kazal type 1(SPINK1) expression and its influence on the prognosis of human hepatocellular carcinoma(HCC) and to explore the underlying molecular mechanisms involved. METHODS: Eighty patients with HCC who underwent curative resection were followed-up with a median observation time of 58.6 months.SPINK1expression was detected in the primary HCC samples by immunohistochemistry . Its role in tumor invasion and metastasis was evaluated in vitro by gene silence using siRNA-mediated approach, rSPINK1 and U0126(an inhibitor of MEK/ERK)...
May 23, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28543863/prmt8-controls-the-pluripotency-and-mesodermal-fate-of-human-embryonic-stem-cells-by-enhancing-the-pi3k-akt-sox2-axis
#8
Ho-Chang Jeong, Soon-Jung Park, Jong-Jin Choi, Young-Hyun Go, Soon-Ki Hong, Ok-Seon Kwon, Joong-Gon Shin, Rae-Kwon Kim, Mi-Ok Lee, Su-Jae Lee, Hyoung Doo Shin, Sung-Hwan Moon, Hyuk-Jin Cha
Basic fibroblast growth factor (bFGF) supplementation is critical to maintain the pluripotency of human pluripotent stem cells (hPSCs) through activation of PI3K/AKT, rather than MEK/ERK pathway. Thus, elaborate molecular mechanisms that preserve PI3K/AKT signaling upon bFGF stimulation may exist in hPSCs. Protein arginine methyltransferases 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under bFGF-deprived conditions...
May 20, 2017: Stem Cells
https://www.readbyqxmd.com/read/28543697/molecular-insights-into-melanoma-brain-metastases
#9
REVIEW
Dana Westphal, Isabella C Glitza Oliva, Heike Niessner
Substantial proportions of patients with metastatic melanoma develop brain metastases during the course of their disease, often resulting in significant morbidity and death. Despite recent advances with BRAF/MEK and immune-checkpoint inhibitors in the treatment of patients who have melanoma with extracerebral metastases, patients who have melanoma brain metastases still have poor overall survival, highlighting the need for further therapy options. A deeper understanding of the molecular pathways involved in the development of melanoma brain metastases is required to develop more brain-specific therapies...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28542422/angelica-dahurica-ethanolic-extract-improves-impaired-wound-healing-by-activating-angiogenesis-in-diabetes
#10
Xiao-Na Zhang, Ze-Jun Ma, Ying Wang, Bei Sun, Xin Guo, Cong-Qing Pan, Li-Ming Chen
Abnormal angiogenesis plays an important role in impaired wound healing and development of chronic wounds in diabetes mellitus. Angelica dahurica radix is a common traditional Chinese medicine with wide spectrum medicinal effects. In this study, we analyzed the potential roles of Angelica dahurica ethanolic extract (ADEE) in correcting impaired angiogenesis and delayed wound healing in diabetes by using streptozotocin-induced diabetic rats. ADEE treatment accelerated diabetic wound healing through inducing angiogenesis and granulation tissue formation...
2017: PloS One
https://www.readbyqxmd.com/read/28539463/braf-fusion-as-a-novel-mechanism-of-acquired-resistance-to-vemurafenib-in-braf-v600e-mutant-melanoma
#11
Atul Kulkarni, Husam Al-Hraishawi, Srilatha Simhadri, Kim M Hirshfield, Suzie Chen, Sharon R Pine, Chandrika Jeyamohan, Levi Sokol, Siraj M Ali, Man Lung Teo, Eileen White, Lorna Rodriguez-Rodriguez, Janice M Mehnert, Shridar Ganesan
Many patients with BRAF (V)(600E) mutant melanoma treated with BRAF inhibitors experience a rapid response, but ultimately develop resistance. Insight into the mechanism of resistance is critical for development of more effective treatment strategies. <br /><br />Experimental Design: Comprehensive genomic profiling of serial biopsies was performed in a patient with a BRAF(V600E) mutant metastatic melanoma who developed resistance to vemurafenib. An AGAP3-BRAF fusion gene, identified in the vemurafenib-resistant tumor, was expressed in BRAF(V600E) melanoma cell lines and its effect on drug sensitivity was evaluated...
May 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28537912/braf-mek-inhibitors-promote-cd47-expression-that-is-reversible-by-erk-inhibition-in-melanoma
#12
Fen Liu, Chen Chen Jiang, Xu Guang Yan, Hsin-Yi Tseng, Chun Yan Wang, Yuan Yuan Zhang, Hamed Yari, Ting La, Margaret Farrelly, Su Tang Guo, Rick F Thorne, Lei Jin, Qi Wang, Xu Dong Zhang
The expression of CD47 on the cancer cell surface transmits "don't eat me" signalling that not only inhibits phagocytosis of cancer cells by phagocytes but also impairs anti-cancer T cell responses. Here we report that oncogenic activation of ERK plays an important role in transcriptional activation of CD47 through nuclear respiratory factor 1 (NRF-1) in melanoma cells. Treatment with BRAF/MEK inhibitors upregulated CD47 in cultured melanoma cells and fresh melanoma isolates. Similarly, melanoma cells selected for resistance to the BRAF inhibitor vemurafenib expressed higher levels of CD47...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537899/nras-mutations-in-cutaneous-t-cell-lymphoma-ctcl-sensitize-tumors-towards-treatment-with-the-multikinase-inhibitor-sorafenib
#13
Michael K Kießling, Jan P Nicolay, Tabea Schlör, Claus-Detlev Klemke, Dorothee Süss, Peter H Krammer, Karsten Gülow
Therapy of cutaneous T cell lymphoma (CTCL) is complicated by a distinct resistance of the malignant T cells towards apoptosis that can be caused by NRAS mutations in late-stage patients. These mutations correlate with decreased overall survival, but sensitize the respective CTCL cells towards MEK-inhibition-induced apoptosis which represents a promising novel therapeutic target in CTCL. Here, we show that the multi-kinase inhibitor Sorafenib induces apoptosis in NRAS-mutated CTCL cells. CTCL cell lines and to a minor extent primary T cells from Sézary patients without NRAS mutations are also affected by Sorafenib-induced apoptosis suggesting a sensitizing role of NRAS mutations for Sorafenib-induced apoptosis...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537897/mek-inhibitors-cobimetinib-and-trametinib-regressed-a-gemcitabine-resistant-pancreatic-cancer-patient-derived-orthotopic-xenograft-pdox
#14
Kei Kawaguchi, Kentaro Igarashi, Takashi Murakami, Tasuku Kiyuna, Thinzar M Lwin, Ho Kyoung Hwang, Jonathan C Delong, Bryan M Clary, Michael Bouvet, Michiaki Unno, Robert M Hoffman
A pancreatic ductal adenocarcinoma (PDAC), obtained from a patient, was grown orthotopically in the pancreatic tail of nude mice to establish a patient-derived orthotopic (PDOX) model. Seven weeks after implantation, PDOX nude mice were divided into the following groups: untreated control (n = 7); gemcitabine (100 mg/kg, i.p., once a week for 2 weeks, n = 7); cobimetinib (5 mg/kg, p.o., 14 consecutive days, n = 7); trametinib (0.3 mg/kg, p.o., 14 consecutive days, n = 7); trabectedin (0.15 mg/kg, i.v., once a week for 2 weeks, n = 7); temozolomide (25 mg/kg, p...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537736/probing-the-cleaning-of-polymeric-coatings-by-nanostructured-fluids-a-qcm-d-study
#15
Martina Raudino, Nicoletta Giamblanco, Costanza Montis, Debora Berti, Giovanni Marletta, Piero Baglioni
Complex fluids composed of water, an organic solvent and a surfactant have been recently employed as cleaning systems to remove hydrophobic materials, such as polymeric coatings, from solid surfaces. The simultaneous presence of surfactants and an organic solvent with good affinity for the polymer was proven necessary for the polymer's removal, but the comprehension of the cleaning mechanism is poorly understood. In this article we investigated the mechanism of removal, highlighting the specific role of each component in the interaction with the polymer film...
May 24, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28537004/mek-inhibitors-in-the-treatment-of-metastatic-melanoma-and-solid-tumors
#16
REVIEW
Antonio M Grimaldi, Ester Simeone, Lucia Festino, Vito Vanella, Martina Strudel, Paolo A Ascierto
The mitogen-activated protein kinase (MAPK) cascade is an intracellular signaling pathway involved in the regulation of cellular proliferation and the survival of tumor cells. Several different mutations, involving BRAF or NRAS, exert an oncogenic effect by activating the MAPK pathway, resulting in an increase in cellular proliferation. These mutations have become targets for new therapeutic strategies in melanoma and other cancers. Selective MEK inhibitors have the ability to inhibit growth and induce cell death in BRAF- and NRAS-mutant melanoma cell lines...
May 23, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28536368/implications-of-a-multi-step-trigger-of-retinal-regeneration-in-the-adult-newt
#17
Hirofumi Yasumuro, Keisuke Sakurai, Fubito Toyama, Fumiaki Maruo, Chikafumi Chiba
The newt is an amazing four-limbed vertebrate that can regenerate various body parts including the retina. In this animal, when the neural retina (NR) is removed from the eye by surgery (retinectomy), both the NR and the retinal pigment epithelium (RPE) eventually regenerate through the process of reprogramming and proliferation of RPE cells. Thus far, we have pursued the onset mechanism of adult newt retinal regeneration. In this study, using an in vitro system, we found that both mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK and β-catenin were involved in cell cycle re-entry of RPE cells...
May 20, 2017: Biomedicines
https://www.readbyqxmd.com/read/28536078/akt-is-critically-involved-in-the-antagonism-of-braf-inhibitor-sorafenib-against-dabrafenib-in-colorectal-cancer-cells-harboring-both-wild-type-and-mutant-v600e-braf-genes
#18
Hongbin Wang, Haitian Quan, Liguang Lou
BRAF, one of the key factors in mitogen-activated protein kinase (MAPK) signaling pathway, plays an important role in cell functions including growth and proliferation. Inhibition of BRAF represents a promising antitumor strategy. Dabrafenib, a type I inhibitor of BRAF interrupting RAF/MEK interaction, has been approved by FDA as a single agent or combined with MEK inhibitor trametinib for the treatment of patients with BRAF V600E mutation-positive advanced melanoma. In the present study, we investigated the feasibility of combined treatment with dabrafenib and sorafenib, type I and type II BRAF inhibitor respectively, on colorectal cancer cells with BRAF V600E mutation...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28534984/ccl21-ccr7-interaction-promotes-cellular-migration-and-invasion-via-modulation-of-the-mek-erk1-2-signaling-pathway-and-correlates-with-lymphatic-metastatic-spread-and-poor-prognosis-in-urinary-bladder-cancer
#19
Yang Xiong, Fang Huang, Xiaozhou Li, Zhi Chen, Deyun Feng, Haiying Jiang, Wei Chen, Xiangyang Zhang
Lymph node metastasis in patients with urinary bladder cancer (UBC) is always associated with poor prognosis and is the determinant for tumor staging and the development of treatment regimens; however, its underlying mechanisms remain to be studied. Immunohistochemical staining of tumor sections from 62 UBC patients was performed using CCR7, D2-40 and CD34 antibodies. We showed that increased CCR7 expression was significantly associated with positive lymph node status (P=0.008), pT3-T4 tumor stage (P=0.015), tumor grade (P=0...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534510/targeting-group-i-p21-activated-kinases-to-control-malignant-peripheral-nerve-sheath-tumor-growth-and-metastasis
#20
G Semenova, D S Stepanova, C Dubyk, E Handorf, S M Deyev, A J Lazar, J Chernoff
Malignant peripheral nerve sheath tumors (MPNSTs) are devastating sarcomas for which no effective medical therapies are available. Over 50% of MPSNTs are associated with mutations in NF1 tumor suppressor gene, resulting in activation of Ras and its effectors, including the Raf/Mek/Erk and PI3K/Akt/mTORC1 signaling cascades, and also the WNT/β-catenin pathway. As Group I p21-activated kinases (Group I Paks, PAK1/2/3) have been shown to modulate Ras-driven oncogenesis, we asked if these enzymes might regulate signaling in MPNSTs...
May 22, 2017: Oncogene
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