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https://www.readbyqxmd.com/read/29222481/hypoxia-inducible-factor-prolyl-4-hydroxylase-1-is-a-convergent-point-in-the-reciprocal-negative-regulation-of-nf-%C3%AE%C2%BAb-and-p53-signaling-pathways
#1
Karim Ullah, Ann-Helen Rosendahl, Valerio Izzi, Ulrich Bergmann, Taina Pihlajaniemi, Joni M Mäki, Johanna Myllyharju
Hypoxia-inducible factor 1α (HIF1α) induces the expression of several hundred genes in hypoxia aiming at restoration of oxygen homeostasis. HIF prolyl-4-hydroxylases (HIF-P4Hs) regulate the stability of HIF1α in an oxygen-dependent manner. Hypoxia is a common feature in inflammation and cancer and the HIF pathway is closely linked with the inflammatory NF-κB and tumor suppressor p53 pathways. Here we show that genetic inactivation or chemical inhibition of HIF-P4H-1 leads to downregulation of proinflammatory genes, while proapoptotic genes are upregulated...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29221144/ucp2-overexpression-enhanced-glycolysis-via-activation-of-pfkfb2-during-skin-cell-transformation
#2
Annapoorna Sreedhar, Petra Petruska, Sumitra Miriyala, Manikandan Panchatcharam, Yunfeng Zhao
Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane transporter which is often upregulated in human cancers. However, how this anion transporter affects tumorigenesis is not well understood. Using the skin cell transformation JB6 model, we demonstrated that UCP2 overexpression activated phosphofructokinase 2/fructose-2,6-bisphosphatase 2 (PFKFB2), a key regulator of glycolysis. In conjunction, upregulation of PFKFB2 expression correlated with elevated fructose 2,6-bisphosphate (Fru-2,6-P2) levels, 6-phosphofructo-1-kinase (PFK-1) activity, glucose uptake, and lactate production...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221137/ev20-sap-a-novel-anti-her-3-antibody-drug-conjugate-displays-promising-antitumor-activity-in-melanoma
#3
Emily Capone, Francesco Giansanti, Sara Ponziani, Alessia Lamolinara, Manuela Iezzi, Annamaria Cimini, Francesco Angelucci, Rossana La Sorda, Vincenzo De Laurenzi, Pier Giorgio Natali, Rodolfo Ippoliti, Stefano Iacobelli, Gianluca Sala
Melanoma is the most biologically aggressive skin cancer of well established constitutive and induced resistance to pharmacological treatment. Despite the recent progresses in immunotherapies, many advanced metastatic melanoma patients still face a significant mortality risk. The aggressive nature of this disease sustains an urgent need for more successful, effective drugs. HER-3 - one of the four member of the tyrosin kinase epidermal growth factor receptors (EGFRs) family- is frequently overexpressed in solid tumors, including melanoma...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220430/postoperative-outcomes-in-ustekinumab-treated-patients-undergoing-abdominal-operations-for-crohn-s-disease
#4
Amy L Lightner, Nicholas P McKenna, Chung Sang Tse, Neil Hyman, Radhika Smith, Gayane Ovsepyan, Phillip Fleshner, Kristen Crowell, Walter Koltun, Marc Ferrante, Andre D'Hoore, Nathalie Lauwers, Bram Verstockt, Antonino Spinelli, Francesca DiCandido, Laura E Raffals, Kellie L Mathis, Edward V Loftus
Introduction: Ustekinumab, a monoclonal antibody targeting interleukins-12 and -23 is used to treat adults with Crohn's disease (CD). We determined the 30-day postoperative infectious complication rate among CD patients who received ustekinumab within 12 weeks prior to an abdominal operation as compared to patients who received anti-tumor necrosis factor (TNF) agents. Methods: A retrospective chart review of adults with CD who underwent an abdominal operation between 1/1/2015 and 5/1/2017 was performed across six sites...
December 6, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29220390/maldi-msi-of-melim-melanoma-searching-for-differences-in-protein-profiles
#5
Roman Guran, Lucie Vanickova, Vratislav Horak, Sona Krizkova, Petr Michalek, Zbynek Heger, Ondrej Zitka, Vojtech Adam
BACKGROUND: Treatment of advanced cutaneous melanoma remains challenging, and new data on melanoma biology are required. The most widely accepted criteria for the prognostic evaluation of melanoma are histopathological and clinical parameters, and the identification of additional tumor markers is thus of paramount importance. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI), an important tool in cancer research, is useful for unraveling the molecular profile of melanoma...
2017: PloS One
https://www.readbyqxmd.com/read/29218605/oxymatrine-sensitizes-the-hacat-cells-to-the-ifn-%C3%AE-pathway-and-downregulates-mdc-icam-1-and-socs1-by-activating-p38-jnk-and-akt
#6
Chun-Jie Gao, Pei-Jun Ding, Li-Li Yang, Xu-Feng He, Meng-Jiao Chen, Dong-Ming Wang, Yan-Xin Tian, Hui-Min Zhang
Decreased interferon (IFN)-γ levels and increased levels of macrophage-derived chemokine (MDC) and intercellular adhesion molecule (ICAM)-1 are known to be involved in allergic skin diseases, such as eczema and atopic dermatitis. Activation of the IFN-γ and its downstream interleukin-12 (IL-12) pathway can correct these diseases. Suppressor of cytokine signaling 1 (SOCS1) is a cytokine signaling inhibitor that blocks downstream pathways of IFN-γ by blocking the mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) signaling pathways...
December 7, 2017: Inflammation
https://www.readbyqxmd.com/read/29218279/non-metastatic-non-melanoma-skin-cancers-our-3-years-of-clinical-experiences
#7
Elif Sari
BACKGROUND: Nonmelanoma skin cancers (NMSC) constitute the largest group of skin cancers. In this study, NMSCs were analyzed retrospectively. METHODS: Between June 2013 and March 2017, demographics and comorbidities of patients underwent reconstructive surgery for NMSC; their risk factors, types, diameters, differentiation, localizations, follow-up times, treatment methods and complications were compared and statistically analyzed. RESULTS: Totally, 163 tumors [111 basal cell carcinoma and 52 cutaneous squamous cell carcinoma (cSCC)] were excized from 148 patients (63 females, 85 males)...
September 2017: World Journal of Plastic Surgery
https://www.readbyqxmd.com/read/29217527/merkel-cell-carcinoma-in-the-age-of-immunotherapy-facts-and%C3%A2-hopes
#8
Aric Colunga, Thomas Pulliam, Paul Nghiem
Merkel cell carcinoma (MCC) is a rare (~2,000 US cases/year) but aggressive neuroendocrine tumor of the skin. For advanced MCC, cytotoxic chemotherapy only infrequently (<10% of cases) offers durable clinical responses (>1 year) suggesting a great need for improved therapeutic options. In 2008, the Merkel cell polyomavirus (MCPyV) was discovered and is clonally integrated in ~80% of MCC tumors. The remaining 20% of MCC tumors have large numbers of UV-associated mutations. Importantly, both the UV-induced-neoantigens in virus-negative tumors and the MCPyV T antigen oncogenes that are required for virus-positive tumor growth are immunogenic...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29215830/-study-of-migration-and-distribution-of-bone-marrow-cells-transplanted-animals-with-b16-melanoma
#9
A F Poveshchenko, A O Solovieva, K E Zubareva, D N Strunkin, O B Gricyk, O V Poveshchenko, A V Shurlygina, V I Konenkov
Purpose. Reveal features migration and distribution of syngeneic bone marrow cells (BMC) and subpopulations (MSC) after transplantation into the recipient carrier B16 melanoma bodies. Methods. We used mouse male and female C57BL/6 mice. Induction of Tumor Growth: B16 melanoma cells implanted subcutaneously into right hind paw of female C57BL/6 mice at a dose of 2.5 x 105 cells / mouse. migration study in vivo distribution and BMC and MSC was performed using genetic markers - Y-chromosome specific sequence line male C57Bl/6 syngeneic intravenous transplantation in females using the polymerase chain reaction (PCR) in real time on Authorized Termal Cycler - Light Cycler 480 II / 96 (Roche)...
April 2017: Patologicheskaia Fiziologiia i èksperimental'naia Terapiia
https://www.readbyqxmd.com/read/29215650/phenocopies-in-melanoma-prone-families-with-germ-line-cdkn2a-mutations
#10
Hildur Helgadottir, Håkan Olsson, Margaret A Tucker, Xiaohong R Yang, Veronica Höiom, Alisa M Goldstein
PurposeCarriers of CDKN2A mutations have high risks of melanoma and certain other cancers. In this study we examined the occurrence of tumors among CDKN2A wild type (wt) members of melanoma-prone families with CDKN2A mutations.MethodsSwedish and US melanoma-prone families with CDKN2A mutations were included. Data was collected on tumors diagnosed among family members. Among the CDKN2A mutated families, members with CDKN2A wt status who were diagnosed with melanoma were designated phenocopies.ResultsOf patients with melanoma in the CDKN2A mutated families (n = 266), 7...
December 7, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29215446/nasal-septal-cavernous-hemangioma
#11
Ahmet Baki
Hemangiomas are benign tumors originating from the skin, mucosa, muscle, gland, and vascular tissue in the bone. Although it is common in the head and neck region, it is rarely seen in the nasal cavity and paranasal sinuses. Histologically capillary, cavernous, and mixed types are present, the most common is cavernous-type hemangioma. Cavernous hemangiomas in the nasal cavity, generally originated from the lateral nasal wall, cause symptoms as nasal obstruction and epistaxis. In the author's patient, cavernous hemangioma was originated from the nasal septum, where rarely seen...
December 6, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/29215016/low-neurotrophin-receptor-cd271-regulates-phenotype-switching-in-melanoma
#12
Gaetana Restivo, Johanna Diener, Phil F Cheng, Gregor Kiowski, Mario Bonalli, Thomas Biedermann, Ernst Reichmann, Mitchell P Levesque, Reinhard Dummer, Lukas Sommer
Cutaneous melanoma represents the most fatal skin cancer due to its high metastatic capacity. According to the "phenotype switching" model, the aggressive nature of melanoma cells results from their intrinsic potential to dynamically switch from a high-proliferative/low-invasive to a low-proliferative/high-invasive state. Here we identify the low affinity neurotrophin receptor CD271 as a key effector of phenotype switching in melanoma. CD271 plays a dual role in this process by decreasing proliferation, while simultaneously promoting invasiveness...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29214668/photofrin%C3%A2-photodynamic-therapy-with-intratumor-photosensitizer-injection-provides-similar-tumor-response-while-reducing-systemic-skin-photosensitivity-pilot-murine-study
#13
Timothy M Baran
OBJECTIVES: The goal of this study was to compare tumor response to Photofrin® photodynamic therapy using intravenous and intratumoral injection of photosensitizer. Systemic skin photosensitivity and photosensitizer distribution were also compared between the two delivery methods. METHODS: SCCVII tumors were initiated in the hind legs of female C3H mice and grown to a volume of ∼1,000 mm3 . Photofrin® was delivered intravenously via the tail vein at a concentration of 2 mg/kg or intratumorally at concentrations ranging from 0...
December 7, 2017: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/29214112/hypomelanotic-melanoma-detected-by-the-little-red-riding-hood-sign-in-a-patient-with-neurofibromatosis-type-1
#14
Roberta Giuffrida, Maximilian Uranitsch, Karin Schmid, Teresa Deinlein, Fabrizio Favero, Iris Zalaudek
Neurofibromatosis type 1 (NF1) is a genetic disorder commonly associated with an increased risk for development of malignancy, including skin cancers. Herein we describe a case of invasive melanoma occurring in a patient with NF1 and discuss the association between these two diseases, highlighting the importance of comparative clinical and dermoscopic approaches in this category of patients in which the detection of melanoma can be difficult because of the presence of multiple skin tumors.
October 2017: Dermatology Practical & Conceptual
https://www.readbyqxmd.com/read/29214089/systemic-treatment-of-metastatic-conjunctival-melanoma
#15
Simão Pinto Torres, Teresa André, Emanuel Gouveia, Lívio Costa, Maria José Passos
Conjunctival melanoma (CM) is an exceptionally rare tumor, with a propensity for local and distant recurrence, with the lungs, skin, liver, and brain being the most common sites of metastasis. Recent progress in systemic treatments, with checkpoint inhibitors and targeted therapies blocking BRAF and MEK, has redefined the standard of care of advanced unresectable and metastatic melanoma. Although most trials did not include patients with conjunctival melanoma, its close molecular and genetic relationship to cutaneous melanoma might suggest a similar response to these novel agents...
2017: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29212216/naringin-improves-random-skin-flap-survival-in-rats
#16
Liang Cheng, Tingxiang Chen, Qiming Tu, Hang Li, Zhenghua Feng, Zhijie Li, Dingsheng Lin
Background: Random-pattern flap transfer is commonly used to treat soft-tissue defects. However, flap necrosis remains a serious problem. Naringin accelerates angiogenesis by activating the expression of vascular endothelial growth factor (VEGF). In the present study, we investigated whether naringin improves the survival of random skin flaps. Results: Compared with controls, the naringin-treated groups exhibited significantly larger mean areas of flap survival, significantly increased SOD activity and VEGF expression, and significantly reduced MDA level...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211306/telomerase-reverse-transcriptase-promoter-alterations-across-cancer-types-as-detected-by-next-generation-sequencing-a-clinical-and-molecular-analysis-of-423-patients
#17
Maria Schwaederle, Nithya Krishnamurthy, Gregory A Daniels, David E Piccioni, Santosh Kesari, Paul T Fanta, Richard B Schwab, Sandip P Patel, Barbara A Parker, Razelle Kurzrock
BACKGROUND: Telomerase reverse transcriptase (TERT) promoter mutations that may affect telomerase activity have recently been described in human malignancies. The purpose of this study was to investigate the clinical correlates of TERT promoter abnormalities in a large cohort of patients with diverse cancers. METHODS: This study analyzed TERT promoter alterations and clinical characteristics of 423 consecutive patients for whom molecular testing by next-generation sequencing was performed between August 2014 and July 2015...
December 6, 2017: Cancer
https://www.readbyqxmd.com/read/29210715/blistering-and-skin-fragility-due-to-imatinib-therapy-loss-of-laminin-and-collagen-iv-as-a-possible-cause-of-cutaneous-basement-membrane-instability
#18
Sebastian Mühl, Jan Ehrchen, Dieter Metze
Imatinib mesylate (Glivec; Novartis AG, Basel, Switzerland) is a tyrosine kinase inhibitor which is used in the treatment of oncologic diseases like chronic myeloid leukemia and gastrointestinal stroma tumor (GIST). Among cutaneous side effects, bullous reactions are rare. The authors describe the case of a 66-year-old woman developing blistering and skin fragility on her hands, foot, lower legs, and back after intake of imatinib for treatment of GIST. Biopsy showed vacuolar alteration at the dermoepidermal junction (DEJ) associated with a few lymphocytes and a subepidermal blister...
November 22, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/29209327/strategies-to-improve-the-efficacy-of-dendritic-cell-based-immunotherapy-for-melanoma
#19
REVIEW
Kristian M Hargadon
Melanoma is a highly aggressive form of skin cancer that frequently metastasizes to vital organs, where it is often difficult to treat with traditional therapies such as surgery and radiation. In such cases of metastatic disease, immunotherapy has emerged in recent years as an exciting treatment option for melanoma patients. Despite unprecedented successes with immune therapy in the clinic, many patients still experience disease relapse, and others fail to respond at all, thus highlighting the need to better understand factors that influence the efficacy of antitumor immune responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29209060/atr-ftir-spectral-discrimination-between-normal-and-tumorous-mouse-models-of-lymphoma-and-melanoma-from-serum-samples
#20
Hemendra Ghimire, Mahathi Venkataramani, Zhen Bian, Yuan Liu, A G Unil Perera
This study presents, attenuated total reflection Fourier transforms infrared spectroscopy of dried serum samples in an effort to assess biochemical changes induced by non-Hodgkin's lymphoma and subcutaneous melanoma. An EL4 mouse model of non-Hodgkin lymphoma and a B16 mouse model of subcutaneous melanoma are used to extract a snapshot of tumor-associated alteration in the serum. The study of both cancer-bearing mouse models in wild types and their corresponding control types, emphasizes the diagnostic potential of this approach as a screening technique for non-Hodgkin lymphoma and melanoma skin cancer...
December 5, 2017: Scientific Reports
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