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https://www.readbyqxmd.com/read/28325255/mucosal-melanoma-of-the-head-and-neck
#1
REVIEW
Paolo Antonio Ascierto, Remo Accorona, Gerardo Botti, Davide Farina, Piero Fossati, Gemma Gatta, Helen Gogas, Davide Lombardi, Roberto Maroldi, Piero Nicolai, Marco Ravanelli, Vito Vanella
Mucosal melanoma of the head and neck is a very rare and aggressive malignancy with a very poor prognosis. The nasal cavity, paranasal sinuses, and oral cavity are the most common locations. One-, 3- and 5-year survival rates between 2000 and 2007 were 63%, 30% and 20%, respectively. Cigarette smoking seems to be a risk factor even though the evidence for this is very low. Clinical signs and symptoms are usually nonspecific. While surgery is considered the mainstay of treatment for most mucosal melanomas of the head and neck region, radiotherapy has a role in local control of the disease after surgery...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28323731/thymic-carcinoma-with-endobronchial-metastasis-a-case-report
#2
Makoto Nagamata, Yusuke Okuma, Yukio Hosomi, Tsunekazu Hishima
Thymic carcinoma is a rare cancer, accounting for only 1% to 4% of thymic epithelial tumors. Endobronchial metastasis is a rare presentation of these tumors. A 64-year-old man presented with a cough. Lung cancer was suspected because a chest radiograph showed a 7-cm mass in the left pulmonary hilum. Computed tomography showed a mass in the anterior mediastinum and an infiltrate in the upper lobe of the left lung. Bronchoscopy demonstrated bilateral polypoid tumors in the left B bronchus and the right B bronchus...
April 2017: Journal of Bronchology & Interventional Pulmonology
https://www.readbyqxmd.com/read/28322836/radotinib-induces-high-cytotoxicity-in-c-kit-positive-acute-myeloid-leukemia-cells
#3
Sook-Kyoung Heo, Eui-Kyu Noh, Jeong Yi Kim, Jae-Cheol Jo, Yunsuk Choi, SuJin Koh, Jin Ho Baek, Young Joo Min, Hawk Kim
Previously, we reported that radotinib, a BCR-ABL1 tyrosine kinase inhibitor, induced cytotoxicity in acute myeloid leukemia (AML) cells. However, the effects of radotinib in the subpopulation of c-KIT-positive AML cells were unclear. We observed that low-concentration radotinib had more potent cytotoxicity in c-KIT-positive cells than c-KIT-negative cells from AML patients. To address this issue, cell lines with high c-KIT expression, HEL92.1.7, and moderate c-KIT expression, H209, were selected. HEL92.1.7 cells were grouped into intermediate and high c-KIT expression populations...
March 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28319021/engineering-a-growth-sensor-to-select-intracellular-antibodies-in-the-cytosol-of-mammalian-cells
#4
Thuy Duong Nguyen, Hitoshi Takasuka, Yoshihiro Kaku, Satoshi Inoue, Teruyuki Nagamune, Masahiro Kawahara
Intracellular antibodies (intrabodies) are expected to function as therapeutics as well as tools for elucidating in vivo function of proteins. In this study, we propose a novel intrabody selection method in the cytosol of mammalian cells by utilizing a growth signal, induced by the interaction of the target antigen and an scFv-c-kit growth sensor. Here, we challenge this method to select specific intrabodies against rabies virus nucleoprotein (RV-N) for the first time. As a result, we successfully select antigen-specific intrabodies from a naïve synthetic library using phage panning followed by our growth sensor-based intracellular selection method, demonstrating the feasibility of the method...
March 16, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28314314/familial-gastrointestinal-stromal-tumor-with-germline-kit-mutations-accompanying-hereditary-breast-and-ovarian-cancer-syndrome
#5
Yuki Sekido, Seiji Ohigashi, Tsuyoshi Takahashi, Naoki Hayashi, Koyu Suzuki, Seiichi Hirota
BACKGROUND: Familial gastrointestinal stromal tumor (GIST) is a rare disease with germline mutations in the c-kit gene (KIT) or platelet-derived growth factor receptor alpha gene (PDGFRA). We had encountered multiple GISTs in the stomach and small intestine during a screening of ovarian cancer for a woman with hereditary breast and ovarian cancer syndrome (HBOC) with breast cancer susceptibility gene II (BRCA2) mutations. The aim of this study was to examine this case in detail. CASE REPORT: A 65-year-old woman diagnosed with HBOC harboring BRCA2 mutations was found to have multiple tumors in the stomach and small intestine by abdominal screening...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314168/mir-137-downregulates-c-kit-expression-in-acute-myeloid-leukemia
#6
Yanping Hu, Xiaolong Dong, Guoming Chu, Guangrui Lai, Bijun Zhang, Leitong Wang, Yanyan Zhao
The oncogene c-kit plays a vital role in the pathogenesis of acute myeloid leukemia (AML). However, the mechanism of microRNAs targeting c-kit in AML has not been determined in detail. Moreover, the role miR-137 in tumor cell proliferation remains controversial. The aim of this work was to verify whether miR-137 targets c-kit and to research the biological effects of restoring miR-137 expression in leukemia cells. We found that miR-137 binds specifically to the 3'-UTR of c-kit and suppresses the expression and activities of c-kit...
February 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28303135/a-human-lin-cd123-cd127-low-population-endowed-with-ilc-features-and-migratory-capabilities-contributes-to-immunopathological-hallmarks-of-psoriasis
#7
Luz María Mora-Velandia, Octavio Castro-Escamilla, Andrés González Méndez, Cristina Aguilar-Flores, Martha Velázquez-Avila, María Isabel Tussié-Luna, Juan Téllez-Sosa, César Maldonado-García, Fermín Jurado-Santacruz, Eduardo Ferat-Osorio, Jesus Martínez-Barnetche, Rosana Pelayo, Laura C Bonifaz
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127(-) ILC populations and an early ILC precursor (EILP) CD127(low). ILC development has predominately been investigated in mouse models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28301608/loss-of-c-kit-expression-in-thyroid-cancer-cells
#8
Sara Franceschi, Francesca Lessi, Federica Panebianco, Elena Tantillo, Marco La Ferla, Michele Menicagli, Paolo Aretini, Alessandro Apollo, Antonio Giuseppe Naccarato, Ivo Marchetti, Chiara Maria Mazzanti
Papillary thyroid carcinoma is the most frequent histologic type of thyroid tumor. Few studies investigated the role of c-KIT expression in thyroid tumors, suggesting a role for this receptor and its ligand in differentiation and growth control of thyroid epithelium and a receptor loss following malignant transformation. We investigated and correlated c-KIT expression levels and two known markers of thyrocytes differentiation, PAX8 and TTF-1, in malignant and benign cytological thyroid samples. Moreover, we performed functional studies on human papillary thyroid carcinoma cell line to associated c-KIT expression to thyrocytes differentiation and tumor proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28299766/increased-level-of-c-kit-in-semen-of-infertile-patients-with-varicocele
#9
Guorong Jin, Jianrong Liu, Qin Qin, Songdan Gao, Fang Zhang, Yuehong Ma, Caiyun Ding, Lina Dong, Haizhen Yin, Yimin Wang
PURPOSE: Varicocele is the most common risk factor for male infertility, however, not all males with varicocele experience infertility. In fact, most patients with varicocele have normal spermatogenesis. The molecular mechanism of varicocele-associated infertility is yet to be completely understood. The aim of this study is to assess the association of a number of fertility regulatory factors on varicocele associated infertility and to throw light on the mechanism of varicocele-associated infertility...
March 16, 2017: Urology Journal
https://www.readbyqxmd.com/read/28299632/transgenic-expression-of-a-canonical-wnt-inhibitor-kallistatin-is-associated-with-decreased-circulating-cd19-b-lymphocytes-in-the-peripheral-blood
#10
Jeffrey D McBride, Xiaochen Liu, William L Berry, Ralf Janknecht, Rui Cheng, Kelu Zhou, Evangelos V Badiavas, Jian-Xing Ma
Members of the family of serine proteinase inhibitors, such as kallistatin, have been shown to inhibit canonical Wnt-TCF/LEF-β-catenin signaling via their interactions with the Wnt co-receptor LRP6. Yet the effects of transgenic overexpression of anti-Wnt serpins on hematopoiesis and lymphopoiesis are not well known. We studied the effects of human kallistatin (SERPINA4) on Wnt reporter activity in various cell types throughout the hematopoietic system and associated impacts on circulating white blood cell profiles...
March 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28296006/intracoronary-allogeneic-cardiosphere-derived-stem-cells-are-safe-for-use-in-dogs-with-dilated-cardiomyopathy
#11
Michael Taylor Hensley, Junnan Tang, Kathleen Woodruff, Teresa Defrancesco, Sandra Tou, Christina M Williams, Mathew Breen, Kathryn Meurs, Bruce Keene, Ke Cheng
Cardiosphere-derived cells (CDCs) have been shown to reduce scar size and increase viable myocardium in human patients with mild/moderate myocardial infarction. Studies in rodent models suggest that CDC therapy may confer therapeutic benefits in patients with non-ischaemic dilated cardiomyopathy (DCM). We sought to determine the safety and efficacy of allogeneic CDC in a large animal (canine) model of spontaneous DCM. Canine CDCs (cCDCs) were grown from a donor dog heart. Similar to human CDCs, cCDCs express CD105 and are slightly positive for c-kit and CD90...
March 15, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28294314/generation-of-precursor-immature-and-mature-murine-b1-cell-lines-from-c-myc-bcl-xl-overexpressing-pre-bi-cells
#12
Inge Wolf, Corinne Bouquet, Friederike Naumann, Fritz Melchers
Deregulated expression of c-myc and bcl-xL is long known to generate transformed B cells in humans and mice. We overexpressed these genes to induce in vitro and in vivo differentiation of fetal liver-derived mouse pre-BI cells to B1-lineage pre-BII-like, immature and mature B-cell lines and to Ig-secreting cells. In vitro, doxycycline-controlled c-myc/bcl-xL-overexpressing CD19(+) CD93(+) c-kikt(+) IgM(-) pre-BI cells differentiate to and survive as CD19(+) CD93(+) c-kit(-) IgM(+) immature B1 cells. Timed CpG-stimulation of these oncogene-overexpressing pre-B or immature B1 cells generates either CD19(+) CD93(low) c-kit(-) IgM(-) SLC(-) pre-BII-like, or IgM(+) MHCII(+) CD73(+) CD80(+) CD40(+) mature B1-cell lines and IgM-secreting B1 cells in vitro and fixes their state of differentiation...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28288693/uterine-epithelioid-leiomyosarcoma-with-c-kit-expression-and-ywhae-gene-rearrangement-a-case-report-of-a-diagnostic-pitfall-of-uterine-sarcoma
#13
Terufumi Kubo, Shintaro Sugita, Ryuichi Wada, Noriaki Kikuchi, Masahiro Iwasaki, Yumika Ito, Taro Sugawara, Hiromi Fujita, Makoto Emori, Ryoichi Tanaka, Hiroshi Hirano, Tsuyoshi Saito, Tadashi Hasegawa
BACKGROUND: Uterine sarcoma is a rare tumor that is often difficult to classify based on morphological and immunohistochemical analysis alone. Limited access to molecular biological analysis in routine practice would hinder making a definitive diagnosis. CASE PRESENTATION: In this report, we describe a case of a mesenchymal tumor arising from the uterine cervix in a 52-year-old woman. From microscopic morphology of the resected specimen, epithelioid leiomyosarcoma, high-grade endometrial stromal sarcoma, or uterine gastrointestinal stromal tumor (GIST) were considered as differential diagnoses...
March 14, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28288180/neuroendocrine-carcinoma-of-the-esophagus-clinicopathological-and-immunohistochemical-features-of-14-cases
#14
Akinori Egashira, Masaru Morita, Reiko Kumagai, Ken-Ichi Taguchi, Masanobu Ueda, Shohei Yamaguchi, Manabu Yamamoto, Kazuhito Minami, Yasuharu Ikeda, Yasushi Toh
BACKGROUND: Neuroendocrine carcinoma (NEC) of the esophagus is a rare and highly aggressive disease but the biological features are poorly understood. The objective of this study was to analyze the clinicopathological and immunohistochemical features of NEC of the esophagus. METHODS: Fourteen patients diagnosed with NEC of the esophagus from 1998 to 2013 were included in this study. Clinicopathologic features, therapeutic outcomes and immunohistochemical results were analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/28284757/c-kit-positive-cardiac-stem-cells-and-bone-marrow-derived-mesenchymal-stem-cells-synergistically-enhance-angiogenesis-and-improve-cardiac-function-after-myocardial-infarction-in-a-paracrine-manner
#15
Luer Bao, Qingshu Meng, Yuan Li, Shengqiong Deng, Zuoren Yu, Zhongmin Liu, Lin Zhang, Huimin Fan
BACKGROUND: Stem cell transplantation offers a promising treatment for heart failure. Recent studies show that both c-kit positive cardiac stem cells (CSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) are good candidates for stem cell therapy to treat heart failure. However, the exact mechanism of stem cell therapy in improving cardiac function of ischemic cardiomyopathy is not fully known. Our objective was to test our hypothesis that CSCs and/or BM-MSCs repair the damaged heart by boosting post-myocardial infarction (MI) angiogenesis in a paracrine manner...
March 8, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28284084/synthesis-and-evaluation-of-7-substituted-5-6-dihydrobenzo-c-acridine-derivatives-as-new-c-kit-promoter-g-quadruplex-binding-ligands
#16
Qian-Liang Guo, Hua-Fei Su, Ning Wang, Sheng-Rong Liao, Yu-Ting Lu, Tian-Miao Ou, Jia-Heng Tan, Ding Li, Zhi-Shu Huang
It has been shown that treatment of cancer cells with c-KIT G-quadruplex binding ligands can reduce their c-KIT expression levels thus inhibiting cell proliferation and inducing cell apoptosis. Herein, a series of new 7-substituted-5,6-dihydrobenzo[c]acridine derivatives were designed and synthesized. Subsequent biophysical evaluation demonstrated that the derivatives could effectively bind to and stabilize c-KIT G-quadruplex with good selectivity against duplex DNA. It was found that 12-N-methylated derivatives with a positive charge introduced at 12-position of 5,6-dihydrobenzo[c]acridine ring had similar binding affinity but lower stabilizing ability to c-KIT G-quadruplex DNA, compared with those of nonmethylated derivatives...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28283060/decoupling-the-functional-pleiotropy-of-stem-cell-factor-by-tuning-c-kit-signaling
#17
Chia Chi M Ho, Akanksha Chhabra, Philipp Starkl, Peter-John Schnorr, Stephan Wilmes, Ignacio Moraga, Hye-Sook Kwon, Nicolas Gaudenzio, Riccardo Sibilano, Tom S Wehrman, Milica Gakovic, Jonathan T Sockolosky, Matthew R Tiffany, Aaron M Ring, Jacob Piehler, Irving L Weissman, Stephen J Galli, Judith A Shizuru, K Christopher Garcia
Most secreted growth factors and cytokines are functionally pleiotropic because their receptors are expressed on diverse cell types. While important for normal mammalian physiology, pleiotropy limits the efficacy of cytokines and growth factors as therapeutics. Stem cell factor (SCF) is a growth factor that acts through the c-Kit receptor tyrosine kinase to elicit hematopoietic progenitor expansion but can be toxic when administered in vivo because it concurrently activates mast cells. We engineered a mechanism-based SCF partial agonist that impaired c-Kit dimerization, truncating downstream signaling amplitude...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28277830/can-binimetinib-encorafenib-and-masitinib-be-more-efficacious-than-currently-available-mutation-based-targeted-therapies-for-melanoma-treatment
#18
Megan Turner, Kara Rossfeld, April K S Salama, Douglas Tyler, Georgia Beasley
Historically, there were few effective and durable treatments for metastatic melanoma. Recently, mutation based targeted therapies have revolutionized treatment and outcomes for patients with metastatic melanoma. Specifically, inhibitors aimed at BRAF, NRAS, and C-KIT mutations are now commonly used in treatment for patients harboring the specific mutations. Areas Covered: A brief review of current BRAF, NRAS, and C-KIT inhibitors provides background for a thorough review of newly developed agents namely binimetinib, a MEK inhibitor, encorafenib a BRAF inhibitor, and masitinib which inhibits C-KIT...
March 3, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28276465/cytochrome-p450s-in-human-immune-cells-regulate-il-22-and-c-kit-via-an-ahr-feedback-loop
#19
Renate Effner, Julia Hiller, Stefanie Eyerich, Claudia Traidl-Hoffmann, Knut Brockow, Massimo Triggiani, Heidrun Behrendt, Carsten B Schmidt-Weber, Jeroen T M Buters
The mechanisms how environmental compounds influence the human immune system are unknown. The environmentally sensitive transcription factor aryl hydrocarbon receptor (AHR) has immune-modulating functions and responds to small molecules. Cytochrome P4501 enzymes (CYP1) act downstream of the AHR and metabolize small molecules. However, it is currently unknown whether CYP1 activity is relevant for immune modulation. We studied the interdependence of CYP1 and AHR in human primary immune cells using pharmacological methods...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28273719/depletion-of-microglia-exacerbates-postischemic-inflammation-and-brain-injury
#20
Wei-Na Jin, Samuel Xiang-Yu Shi, Zhiguo Li, Minshu Li, Kristofer Wood, Rayna J Gonzales, Qiang Liu
Brain ischemia elicits microglial activation and microglia survival depend on signaling through colony-stimulating factor 1 receptor (CSF1R). Although depletion of microglia has been linked to worse stroke outcomes, it remains unclear to what extent and by what mechanisms activated microglia influence ischemia-induced inflammation and injury in the brain. Using a mouse model of transient focal cerebral ischemia and reperfusion, we demonstrated that depletion of microglia via administration of the dual CSF1R/c-Kit inhibitor PLX3397 exacerbates neurodeficits and brain infarction...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
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