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mitosis in melanoma

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https://www.readbyqxmd.com/read/29675108/increased-aurka-gene-copy-number-correlates-with-poor-prognosis-and-predicts-the-efficacy-of-high-dose-interferon-therapy-in-acral-melanoma
#1
Junya Yan, Jiayi Yu, Xiaowen Wu, Tianxiao Xu, Huan Yu, Jie Dai, Meng Ma, Huan Tang, Longwen Xu, Zhihong Chi, Lu Si, Xinan Sheng, Chuanliang Cui, Yan Kong, Jun Guo
Background: AURKA kinase is an essential serine/threonine kinase for mitosis and chromosome stability. The aberrant amplification and overexpression of AURKA are commonly observed in various types of cancer, including cutaneous melanoma. However, the status and the clinical significance of AURKA copy number (CN) in acral melanoma (AM) have not been fully elucidated. Methods: Four hundred and seventy-two AM samples were included in the study. AURKA CN was examined using the QuantiGenePlex DNA Assay. We analysed the relationship of AURKA CN to clinicopathological characteristics and survival of patients with AM...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29670085/a-trib2-p38-axis-controls-myeloid-leukaemia-cell-cycle-and-stress-response-signalling
#2
Mara Salomé, Aoife Magee, Krisha Yalla, Shahzya Chaudhury, Evgenia Sarrou, Ruaidhrí J Carmody, Karen Keeshan
Trib2 pseudokinase is involved in the etiology of a number of cancers including leukaemia, melanoma, ovarian, lung and liver cancer. Both high and low Trib2 expression levels correlate with different types of cancer. Elevated Trib2 expression has oncogenic properties in both leukaemia and lung cancer dependent on interactions with proteasome machinery proteins and degradation of transcription factors. Here, we demonstrated that Trib2 deficiency conferred a growth and survival advantage both at steady state and in stress conditions in leukaemia cells...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29660568/interdigitating-dendritic-cell-sarcoma-clinicopathologic-study-of-8-cases-with-review-of-the-literature
#3
REVIEW
Tian Xue, Xiang-Nan Jiang, Wei-Ge Wang, Xiao-Yan Zhou, Xiao-Qiu Li
To investigate the clinicopathologic features and differential diagnoses of interdigitating dendritic cell sarcoma (IDCS), the clinical, morphological and immunohistochemical features of eight cases of IDCS were collected and analyzed. Three patients were males and five were females, the mean age and the median age were 56.5 years and 57 years respectively. Clinically, the majority of cases involved lymph nodes. Microscopically, neoplastic cells were spindle or ovoid, forming fascicles or whorls. Every case had active mitosis figures...
March 30, 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29535131/endogenous-replication-stress-marks-melanomas-sensitive-to-chk1-inhibitors-in-vivo
#4
Zay Yar Oo, Alexander J Stevenson, Martina A Proctor, Sheena M Daignault, Sebastian Walpole, Catherine Lanagan, Mu-Su Chen, Dubravka Skalamera, Loredana Spoerri, Stephen Ainger, Richard A Sturm, Nikolas K Haass, Brian Gabrielli
PURPOSE: CHEK1 inhibitors (CHEK1i) have single agent activity in vitro and in vivo. Here we have investigated the molecular basis of this activity. EXPERIMENTAL DESIGN: We have assessed a panel of melanoma cell lines for their sensitivity to the CHEK1i GNE-323 and GDC-0575 in vitro and in vivo. The effects of these compounds on responses to DNA replication stress were analyzed in the hypersensitive cell lines. RESULTS: A subset of melanoma cell lines are hypersensitive to CHEK1i-induced cell death in vitro, and the drug effectively inhibits tumour growth in vivo...
March 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29415335/high-density-of-m2-macrophages-in-acral-lentiginous-melanoma-compared-to-superficial-spreading-melanoma
#5
M Zúñiga-Castillo, N V Pereira, M N Sotto
AIMS: Acral lentiginous melanoma (ALM) is the most common type of melanoma in people with darker skin phototypes. There is some evidences that the etiology, pathogenesis, risk factors, and natural history of ALM differ from those of superficial spreading melanoma (SSM). ALM behaves more aggressively than SSM, but the biological explanation for these differences remains unknown. The presence of one subtype of macrophages, termed M2-macrophage (M2-M), has been found to be related to local progression, metastasis, and poor prognosis in several neoplasms...
February 7, 2018: Histopathology
https://www.readbyqxmd.com/read/29377340/nuclear-pseudoinclusions-in-melanoma-cells-prognostic-fact-or-artifact-the-possible-role-of-golgi-phosphoprotein-3-overexpression-in-nuclear-pseudoinclusions-generation
#6
Piotr Donizy, Maciej Kaczorowski, Przemyslaw Biecek, Agnieszka Halon, Rafal Matkowski
Nuclear pseudoinclusions (NPIs) are classically found in papillary thyroid carcinoma and meningioma. Although NPIs have been described in melanocytic lesions, there is no systematic analysis of potential relationship between NPIs and other clinicopathological characteristics of melanoma. We examined the presence of NPIs in H&E-stained tissue sections form 96 melanomas and analyzed statistical associations with important clinicopathological parameters and tissue immunoreactivity for selected proteins involved in epithelial-mesenchymal transition (SPARC, N-cadherin), cell adhesion and mobility (ALCAM, ADAM-10), regulation of mitosis (PLK1), cell survival (FOXP1) and functioning of Golgi apparatus (GOLPH3, GP73)...
January 29, 2018: Pathology International
https://www.readbyqxmd.com/read/29278418/aberrant-dna-methylation-is-associated-with-aggressive-clinicopathological-features-and-poor-survival-in-cutaneous-melanoma
#7
B de Unamuno Bustos, R Murria Estal, G Pérez Simó, J Simarro Farinos, C Pujol Marco, M Navarro Mira, V Alegre de Miquel, R Ballester Sánchez, V Sabater Marco, M Llavador Ros, S Palanca Suela, R Botella Estrada
BACKGROUND: Promoter methylation of tumor suppressor genes (TSGs) has recently been implicated in the pathogenesis of several types of cancer. Regarding melanoma, over a hundred genes that contribute to its pathogenesis have been identified to be aberrantly hypermethylated. This is a retrospective observational study that aims to analyze the prevalence of CpG island methylation in a series of primary melanoma, to identify the associations with the main clinicopathological features, and to explore the prognostic significance of methylation in melanoma survival...
December 26, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29247507/clinicopathological-characteristics-of-cutaneous-malignant-melanoma-in-patients-at-a-tertiary-hospital-in-macaronesia-survival-as-a-function-of-locoregional-prognostic-factors-per-the-american-joint-committee-on-cancer
#8
Ricardo Fernández-de-Misa Cabrera, Benjamín González Delgado, Luisa E Gambra Michel, Cristian Casale, Antonio Lopez Figueroa, Jon Uña Gorospe, José C Martínez Cedrés, Miguel A Cabrera Suárez, Sofía Garrido Ríos, Noelia Hernández Hernández, Alejandro Tébar Díaz, Aitana Sánchez Barrios, Ana Allende Riera, Antonio Perera Molinero
BACKGROUND: Despite suffering high ultraviolet radiation levels, few data on malignant melanoma (MM) in Macaronesia are available. METHODS: Observational study of cutaneous MM cases diagnosed during a period of 12 years at a tertiary hospital in Canary Islands. RESULTS: A total of 532 patients (female/male = 1.4) with an average age of 56 years were included; 5% developed more than one MM, and 7% reported family history of MM. Phototype II (43%), dark eyes (41%), and dark hair (41%) predominated...
February 2018: International Journal of Dermatology
https://www.readbyqxmd.com/read/29229995/lysyl-oxidase-like-3-is-required-for-melanoma-cell-survival-by-maintaining-genomic-stability
#9
Patricia G Santamaría, Alfredo Floristán, Bárbara Fontanals-Cirera, Alberto Vázquez-Naharro, Vanesa Santos, Saleta Morales, Lourdes Yuste, Héctor Peinado, Antonio García-Gómez, Francisco Portillo, Eva Hernando, Amparo Cano
Lysyl oxidase-like 3 (LOXL3) is a member of the lysyl oxidase family comprising multifunctional enzymes with depicted roles in extracellular matrix maturation, tumorigenesis, and metastasis. In silico expression analyses followed by experimental validation in a comprehensive cohort of human cell lines revealed a significant upregulation of LOXL3 in human melanoma. We show that LOXL3 silencing impairs cell proliferation and triggers apoptosis in various melanoma cell lines. Further supporting a pro-oncogenic role in melanoma, LOXL3 favors tumor growth in vivo and cooperates with oncogenic BRAF in melanocyte transformation...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29187493/-braf-nras-and-c-kit-advanced-melanoma-clinico-pathological-features-targeted-therapy-strategies-and-survival
#10
Giovanni Ponti, Marco Manfredini, Stefano Greco, Giovanni Pellacani, Roberta Depenni, Aldo Tomasi, Monia Maccaferri, Stefano Cascinu
BACKGROUND/AIM: The mutational status of stage III and IV melanomas should be recognized in order to allow for targeted therapies. The aim of our study was the characterization of BRAF, NRAS and C-KIT melanoma patients, in order to define their optimal management. PATIENTS AND METHODS: Between 1991 and 2015, 63 mutated melanoma patients were treated and monitored during their diagnostic and therapeutic management at a single institution. RESULTS: BRAF-mutated melanoma patients were the most common, representing 70% of the study population, while NRAS- and C-KIT-mutated melanoma represented 19% and 11% respectively...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29066916/mutation-analysis-and-copy-number-alterations-of-kif23-in-non-small-cell-lung-cancer-exhibiting-kif23-over-expression
#11
Ann-Louise Vikberg, Tõnu Vooder, Kaie Lokk, Tarmo Annilo, Irina Golovleva
KIF23 was recently suggested to be a potential molecular target for the treatment of lung cancer. This proposal is based on elevated expression of KIF23 in several tumors affecting breast, lung, brain, and liver, and also on the presence of KIF23 mutations in melanoma and colorectal cancer. Recently, we identified a mutation in the KIF23 gene causing a rare hereditary form of dyserythropoietic anemia (CDA III) with predisposition to blood cancer. We suggested that KIF23 overexpression in tumors might be due to the presence of activating somatic mutations, and therefore, mutation screening of the KIF23 in 15 non-small-cell lung cancer (NSCLC) cases with elevated expression level of KIF23 was undertaken...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29042215/a-novel-stilbene-like-compound-that-inhibits-melanoma-growth-by-regulating-melanocyte-differentiation-and-proliferation
#12
Noah A Stueven, Nicholas M Schlaeger, Aaron P Monte, Sheng-Ping L Hwang, Cheng-Chen Huang
Melanoma is the most aggressive form of skin cancer. Current challenges to melanoma therapy include the adverse effects from immunobiologics, resistance to drugs targeting the MAPK pathway, intricate interaction of many signal pathways, and cancer heterogeneity. Thus combinational therapy with drugs targeting multiple signaling pathways becomes a new promising therapy. Here, we report a family of stilbene-like compounds called A11 that can inhibit melanoma growth in both melanoma-forming zebrafish embryos and mouse melanoma cells...
December 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29022485/prevalence-of-%C3%AE-iii-tubulin-tubb3-expression-in-human-normal-tissues-and-cancers
#13
Fermín Person, Waldemar Wilczak, Claudia Hube-Magg, Christoph Burdelski, Christina Möller-Koop, Ronald Simon, Mercedes Noriega, Guido Sauter, Stefan Steurer, Susanne Burdak-Rothkamm, Frank Jacobsen
Microtubules are multifunctional cytoskeletal proteins that are involved in crucial cellular roles including maintenance of cell shape, intracellular transport, meiosis, and mitosis. Class III beta-tubulin (βIII-tubulin, also known as TUBB3) is a microtubule protein, normally expressed in cells of neuronal origin. Its expression was also reported in various other tumor types, such as several types of lung cancer, ovarian cancer, and esophageal cancer. TUBB3 is of clinical relevance as overexpression has been linked to poor response to microtubule-targeting anti-cancer drugs such as taxanes...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28928884/anti-melanoma-activities-of-haspin-inhibitor-chr-6494-deployed-as-a-single-agent-or-in-a-synergistic-combination-with-mek-inhibitor
#14
Lili Han, Peiling Wang, Yang Sun, Sijing Liu, Jun Dai
Background: Melanoma is a heterogeneous malignancy that presents an immense challenge in therapeutic development. Recent approaches targeting the oncogenic MAP kinase pathways have shown tremendous improvement in the overall survival of patients with advanced melanoma. However, there is still an urgent need for identification of new strategies to overcome drug resistances and to improve therapeutic efficacy. Haspin (Haploid Germ Cell-Specific Nuclear Protein Kinase) belongs to a selected group of mitotic kinases and is required for normal mitosis progression...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28875289/-diagnostics-of-malignant-melanoma-of-the-skin-recommendations-of-the-current-s3-guidelines-on-histology-and-molecular-pathology
#15
C Rose
The updated S3 guidelines on malignant melanoma were established in August 2016. The principles of diagnostics and classification are based on the histopathological results from the primary tumor and if necessary the sentinel lymph nodes. The most important factor for prognosis is the tumor thickness according to Breslow and the detection of sentinel node micrometastases. The surgical safety margin after excision is dependent on the tumor thickness. Furthermore, ulceration of the primary tumor and presence of mitosis in melanomas less than 1 mm in thickness are also considered in the T‑classification...
September 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28855232/molecular-mechanisms-of-inflammasome-signaling
#16
REVIEW
Anukriti Mathur, Jenni A Hayward, Si Ming Man
The inflammasome is a macromolecular protein complex that mediates proteolytic cleavage of pro-IL-1β and -IL-18 and induces cell death in the form of pyroptosis. Certain nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), or tripartite motif (TRIM) family receptors trigger the assembly of an inflammasome in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Recent studies have revealed a multitude of host components and signals that are essential for controlling canonical and noncanonical inflammasome activation and pyroptosis...
February 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28842323/associations-of-statins-and-diabetes-with-diagnosis-of-ulcerated-cutaneous-melanoma
#17
Lena A von Schuckmann, David Smith, Maria Celia B Hughes, Maryrose Malt, Jolieke C van der Pols, Kiarash Khosrotehrani, Bernard M Smithers, Adele C Green
Ulcerated primary melanomas are associated with an inflammatory tumor microenvironment. We hypothesized that systemic proinflammatory states and anti-inflammatory medications are also associated with a diagnosis of ulcerated melanoma. In a cross-sectional study of 787 patients with newly diagnosed clinical stage IB or II melanoma, we estimated odds ratios for the association of proinflammatory factors (high body mass index, diabetes, cardiovascular disease, hypertension, and smoking) or the use of anti-inflammatory medications (statins, aspirin, corticosteroids, and nonsteroidal anti-inflammatory drugs), with ulcerated primary melanoma using regression models and subgroup analyses to control for melanoma thickness and mitotic rate...
December 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28750139/is-mitotic-rate-still-useful-in-the-management-of-patients-with-thin-melanoma
#18
MULTICENTER STUDY
A Tejera-Vaquerizo, G Pérez-Cabello, L Marínez-Leborans, E Gallego, V Oliver-Martínez, P Martín-Cuevas, S Arias-Santiago, J Aneiros-Fernández, E Herrera-Acosta, V Traves, E Herrera-Ceballos, E Nagore
BACKGROUND: T1 melanoma substaging was recently modified by the American Joint Committee on Cancer (AJCC). Although sentinel lymph node (SLN) positivity is the most important prognostic factor in melanoma, there is a lack of consensus on whether SLN biopsy should be performed in patients with thin melanoma (≤1 mm). OBJECTIVE: The main aim of this study was to investigate predictors of SLN positivity in patients with thin melanoma, with a special emphasis on mitotic rate...
December 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28717212/a-clinicopathological-analysis-of-153-acral-melanomas-and-the-relevance-of-mechanical-stress
#19
Yi-Shuan Sheen, Yi-Hua Liao, Ming-Hsien Lin, Jau-Shiuh Chen, Jau-Yu Liau, Yu-Ju Tseng, Chih-Hung Lee, Yih-Leong Chang, Chia-Yu Chu
The pathogenesis of melanomas emerging in plantar surfaces remains unclear; however, mechanical stress has been reported to increase the formation of melanomas. In this study, we conducted a multicenter retrospective analysis of 153 acral melanomas diagnosed between 2000 and 2015 in Taiwan. The male-to-female ratio of the patients in question was 1:1.28, and the mean age at diagnosis was 68 years. We examined whether melanomas which developed in different areas of the patients' soles differed in their associations with various clinicopathological characteristics and survival...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28688635/melphalan-hypoxic-perfusion-with-hemofiltration-for-melanoma-locoregional-metastases-in-the-pelvis
#20
Stefano Guadagni, Giammaria Fiorentini, Marco Clementi, Giancarlo Palumbo, Alessandro Chiominto, Sonia Cappelli, Francesco Masedu, Marco Valenti
BACKGROUND: For patients with melanoma metastases in the pelvic and groin regions, the median survival time (MST) was 8 mo with old treatments, whereas today is approximately 20 mo with new target therapy and novel immunotherapy. Unfortunately, approximately 30% of patients are nonresponsive to these new drugs. MATERIALS AND METHODS: Thirty-six patients, previously progressing after standard treatments, collectively received 146 melphalan (30 mg/m(2)) hypoxic pelvic perfusions with hemofiltration, in association with palliative excision in most cases...
July 2017: Journal of Surgical Research
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