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https://www.readbyqxmd.com/read/29778085/braf-and-mek-inhibitor-therapy-eliminates-nestin-expressing-melanoma-cells-in-human-tumors
#1
Deon B Doxie, Allison R Greenplate, Jocelyn S Gandelman, Kirsten E Diggins, Caroline E Roe, Kimberly B Dahlman, Jeffrey A Sosman, Mark C Kelley, Jonathan M Irish
Little is known about the in vivo impacts of targeted therapy on melanoma cell abundance and protein expression. Here, 21 antibodies were added to an established melanoma mass cytometry panel to measure 32 cellular features, distinguish malignant cells, and characterize dabrafenib and trametinib responses in BRAFV 600mut melanoma. Tumor cells were biopsied before neoadjuvant therapy and compared to cells surgically resected from the same site after 4 weeks of therapy. Approximately 50,000 cells per tumor were characterized by mass cytometry and computational tools t-SNE/viSNE, FlowSOM, and MEM...
May 19, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29777728/testosterone-induced-downregulation-of-migration-and-proliferation-in-human-umbilical-vein-endothelial-cells-by-androgen-receptor-dependent-and-independent-mechanisms
#2
Aulona Gaba, Mario Mairhofer, Zyhdi Zhegu, Nadja Leditznig, Ladislaus Szabo, Walter Tschugguel, Christian Schneeberger, Iveta Yotova
Recent research has emphasized the potential unfavorable effects of declining testosterone (T) levels in men and the putative beneficial effect of androgen therapy in select women. Some controversy surrounding the mechanism of action and the effects of T on endothelium remains. In this study, we evaluated the mechanism of T action on pooled primary Human Umbilical Vein Endothelial Cells (HUVEC) of mixed gender by focusing on two important processes, proliferation and migration. In our in vitro model system, we found that only the supra-physiological dose of T affected these two processes irrespective of the ratio of male to female cells in the pools...
May 16, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29777657/mcv-mir-m1-targets-the-host-cell-immune-response-resulting-in-the-attenuation-of-neutrophil-chemotaxis
#3
P Akhbari, D Tobin, K Poterlowicz, W Roberts, J R Boyne
Virus-encoded miRNAs are emerging as key regulators of persistent infection and host-cell immune evasion. Merkel cell polyomavirus (MCPyV), the predominant aetiological agent of Merkel cell carcinoma (MCC), encodes a single miRNA, MCV-miR-M1, which targets the oncogenic MCPyV large T antigen (LT). MCV-miR-M1 has previously been shown to play an important role in establishment of long-term infection, however, the underlying mechanism is not fully understood. A key unanswered question is whether, in addition to auto-regulating LT, MCV-miR-M1 also targets cellular transcripts to orchestrate an environment conducive for persistent infection...
May 16, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29777577/autologous-bone-marrow-mesenchymal-stem-cells-improve-the-quality-and-stability-of-vascularized-flap-surgery-of-irradiated-skin-in-pigs
#4
Christine Linard, Michel Brachet, Carine Strup-Perrot, Bruno L'homme, Elodie Busson, Claire Squiban, Valerie Holler, Michel Bonneau, Jean-Jacques Lataillade, Eric Bey, Marc Benderitter
Cutaneous radiation syndrome has severe long-term health consequences. Because it causes an unpredictable course of inflammatory waves, conventional surgical treatment is ineffective and often leads to a fibronecrotic process. Data about the long-term stability of healed wounds, with neither inflammation nor resumption of fibrosis, are lacking. In this study, we investigated the effect of injections of local autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs), combined with plastic surgery for skin necrosis, in a large-animal model...
May 18, 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29777397/telomeres-and-telomerase-during-human-papillomavirus-induced-carcinogenesis
#5
REVIEW
Anna Pańczyszyn, Ewa Boniewska-Bernacka, Grzegorz Głąb
Human papillomaviruses (HPVs) belong to a small spherical virus family and are transmitted through direct contact, most often through sexual behavior. More than 200 types of HPV are known, a dozen or so of which are classified as high-risk viruses (HR HPV) and may contribute to the development of cervical cancer. HPV is a small virus with a capsid composed of L1 and L2 proteins, which are crucial for entry to the cell. The infection begins at the basal cell layer and progresses to involve cells from higher layers of the cervical epithelium...
May 18, 2018: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29777374/the-tenascin-c-derived-peptide-vswrapta-promotes-neuronal-branching-via-transcellular-activation-of-the-focal-adhesion-kinase-fak-and-the-erk1-2-signaling-pathway-in-vitro
#6
Marvin Jarocki, Omar Sallouh, Ralf Weberskirch, Andreas Faissner
The central nervous system (CNS) of mammals has a limited regeneration capacity after traumatic events, which causes chronic functional disability. The development of biomaterials aims at providing support for the regeneration process. One strategy integrates peptides that mimic functional domains of extracellular matrix (ECM) or cell adhesion molecules with synthetic polymers designed to present growth-supporting cues to the neuronal microenvironment. Thus, small peptide sequences originating from molecules of the ECM may serve as promising bio-additives, acting as artificial matricryptins to gear cellular processes...
May 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29777294/impact-of-residual-frontal-recess-cells-on-frontal-sinusitis-after-endoscopic-sinus-surgery
#7
Tsuguhisa Nakayama, Daiya Asaka, Akihito Kuboki, Tetsushi Okushi, Hiromi Kojima
PURPOSE: Endoscopic sinus surgery (ESS) is a well-established treatment for chronic rhinosinusitis (CRS). However, ESS for frontal sinusitis remains complicated and challenging. The aim of this study was to identify the relationship between residual frontal recess cells and primary ESS failure in the frontal sinus. METHODS: We prospectively collected information on 214 sides of 129 patients with CRS who underwent standard ESS from June 2010 to May 2011. To identify risk factors, we retrospectively analyzed clinical data and computed tomography (CT) images before and 3 months after surgery...
May 18, 2018: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/29776594/gearing-up-t-cell-immunotherapy-in-cervical-cancer
#8
REVIEW
Shilpa Raghuvanshi Chauhan, Mausumi Bharadwaj
The World Health Organization estimates more than 270,000 deaths annually by cervical cancer. Present vaccines are prophylactic in nature which cannot treat huge bulk of cervical cancer patients worldwide. Available therapies like radiotherapy, chemotherapy, or surgery are not effective in high-grade lesion, and hence, there is an unmet medical need for an effective form of therapy. T cells play a significant role in cervical cancer pathogenesis as human papilloma virus uses multiple mechanisms that dodge host T-cell immune-surveillance aiding in persistence of infection and establishment of cancer...
April 22, 2018: Current Problems in Cancer
https://www.readbyqxmd.com/read/29776592/response-to-metals-treatment-of-fra1-a-member-of-the-ap-1-transcription-factor-family-in-p-lividus-sea-urchin-embryos
#9
Roberta Russo, Rosa Bonaventura, Marco Chiaramonte, Caterina Costa, Valeria Matranga, Francesca Zito
Lithium (Li), Nickel (Ni), and Zinc (Zn) are metals normally present in the seawater, although they can have adverse effects on the marine ecosystem at high concentrations by interfering with many biological processes. These metals are toxic for sea urchin embryos, affecting their morphology and developmental pathways. In particular, they perturb differently the correct organization of the embryonic axes (animal-vegetal, dorso-ventral): Li is a vegetalizing agent and Ni disrupts the dorso-ventral axis, while Zn has an animalizing effect...
May 5, 2018: Marine Environmental Research
https://www.readbyqxmd.com/read/29775725/anti-hepatitis-c-virus-activity-and-synergistic-effect-of-nymphaea-alba-extracts-and-bioactive-constituents-in-liver-infected-cells
#10
Sidra Rehman, Usman Ali Ashfaq, Bushra Ijaz, Sheikh Riazuddin
BACKGROUND: Without an effective vaccine, hepatitis C virus (HCV) remains a global threat, inflicting 170-300 million carriers worldwide at risk of cirrhosis and hepatocellular carcinoma (HCC). Though various direct acting antivirals have been redeemed the hepatitis C treatment, a few restraints persist including possible side effects, viral resistance emergence, excessive cost which restricts its availability to a common person. HYPOTHESIS: There is no preventive HCV vaccine available today so the discovery of potent antiviral natural flora and their bioactive constituents may help to develop preventive cures against HCV infection...
May 15, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29774940/-prognostic-analysis-and-clinicopathological-features-of-20-patients-with-appendiceal-neuroendocrine-neoplasms
#11
Weilin Mao, Yang Lyu, Ning Pu, Jian'ang Li, Baobao Xin, Wenqi Chen, Dayong Jin, Wenhui Lou, Xuefeng Xu
OBJECTIVE: To investigate clinicopathological features and prognostic factors of appendiceal neuroendocrine neoplasms(a-NEN). METHODS: Clinical data of 20 patients diagnosed with a-NEN at Zhongshan Hospital of Fudan University between January 2000 and December 2016 were retrospectively analyzed. Pathological diagnosis was based on the WHO classification criteria of digestive system tumors (2010 edition). Based on the mitotic count and Ki-67 index, a-NENs were divided into grade 1 neuroendocrine tumor (NET G1), grade 2(G2) NET G2) and grade 3 (neuroendocrine carcinoma, NEC)...
May 25, 2018: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/29774090/strong-sod2-expression-and-hpv-16-18-positivity-are-independent-events-in-cervical-cancer
#12
Silvia Helena Rabelo-Santos, Lara Termini, Enrique Boccardo, Sophie Derchain, Adhemar Longatto-Filho, Maria Antonieta Andreoli, Maria Cecília Costa, Rafaella Almeida Lima Nunes, Liliana Aparecida Lucci Ângelo-Andrade, Luisa Lina Villa, Luiz Carlos Zeferino
It is well known that persistent infection with high-risk HPV (hr-HPV), mostly HPV-16 and 18, is the main cause of cervical cancer development. Manganese superoxide dismutase (MnSOD or SOD2) are highly expressed in different neoplasia. The present study investigated SOD2 protein expression and the presence of hr-HPV types in 297 cervical samples including non-neoplastic tissue, cervical intraepithelial neoplasia grade 3 (CIN3), squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Strong SOD2 expression was significantly higher in ADC (82%) than CIN3 (52%) or SCC (64%)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774053/postherpes-simplex-encephalitis-a-case-series-of-viral-triggered-autoimmunity-synaptic-autoantibodies-and-response-to-therapy
#13
Harry Alexopoulos, Sofia Akrivou, Sotiria Mastroyanni, Maria Antonopoulou, Argirios Dinopoulos, Melpo Giorgi, Kostas Konstantinou, Evangelos Kouremenos, Maria Lariou, Dimitrios Naoumis, Efterpi Pavlidou, Evaggelos Pavlou, Konstantinos Voudris, Panayotis Vlachoyiannopoulos, Marinos C Dalakas
Background: Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. Patient/Methods: Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29774030/changes-in-the-tcr%C3%AE-repertoire-and-tumor-immune-signature-from-a-cutaneous-melanoma-patient-immunized-with-the-csf-470-vaccine-a-case-report
#14
Mariana Aris, Alicia Inés Bravo, María Betina Pampena, Paula Alejandra Blanco, Ibel Carri, Daniel Koile, Patricio Yankilevich, Estrella Mariel Levy, María Marcela Barrio, José Mordoh
The allogeneic therapeutic vaccine CSF-470 has demonstrated a significant benefit over medium-dose IFNα2b in the distant metastasis-free survival for stages IIB-IIC-III cutaneous melanoma patients in a randomized phase II/III clinical trial (CASVAC-0401, NCT01729663). At the end of the 2-year CSF-470 immunization protocol, patient #006 developed several lung and one subcutaneous melanoma metastases; this later was excised. In this report, we analyzed the changes throughout vaccination of immune populations in blood and in the tumor tissue, with special focus on the T-cell repertoire...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773895/crispr-cas9-system-targeting-regulatory-genes-of-hiv-1-inhibits-viral-replication-in-infected-t-cell-cultures
#15
Youdiil Ophinni, Mari Inoue, Tomohiro Kotaki, Masanori Kameoka
The CRISPR/Cas9 system provides a novel and promising tool for editing the HIV-1 proviral genome. We designed RNA-guided CRISPR/Cas9 targeting the HIV-1 regulatory genes tat and rev with guide RNAs (gRNA) selected from each gene based on CRISPR specificity and sequence conservation across six major HIV-1 subtypes. Each gRNA was cloned into lentiCRISPRv2 before co-transfection to create a lentiviral vector and transduction into target cells. CRISPR/Cas9 transduction into 293 T and HeLa cells stably expressing Tat and Rev proteins successfully abolished the expression of each protein relative to that in non-transduced and gRNA-absent vector-transduced cells...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773601/combinatorial-targeting-of-xpo1-and-flt3-exerts-synergistic-anti-leukemia-effects-through-induction-of-differentiation-and-apoptosis-in-flt3-mutated-acute-myeloid-leukemias-from-concept-to-clinical-trial
#16
Weiguo Zhang, Charlie Ly, Jo Ishizawa, Hong Mu, Vivian Ruvolo, Sharon Shacham, Naval Daver, Michael Andreeff
Targeted therapies against FLT3-mutated acute myeloid leukemia have shown limited clinical efficacy primarily because of the acquisition of secondary mutations in FLT3 and persistent activation of downstream pro-survival pathways such as MEK/ERK, PI3K/AKT, and STAT5. Activation of these additional kinases may also result in phosphorylation of tumor suppressor proteins promoting their nuclear export. Thus, co-targeting nuclear export proteins (i.e., XPO1) and FLT3 concomitantly may be therapeutically effective...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773597/hematopoietic-stem-cell-loss-and-hematopoietic-failure-in-severe-aplastic-anemia-is-driven-by-macrophages-and-aberrant-podoplanin-expression
#17
Amanda McCabe, Julianne N P Smith, Angelica Costello, Jackson Maloney, Divya Katikaneni, Katherine C MacNamara
Severe aplastic anemia results from profound hematopoietic stem cell loss. T cells and interferon gamma have long been associated with severe aplastic anemia, yet the underlying mechanisms driving hematopoietic stem cell loss remain unknown. Using a mouse model of severe aplastic anemia, we demonstrate that interferon gamma-dependent hematopoietic stem cell loss required macrophages. Interferon gamma was necessary for bone marrow macrophage persistence, despite loss of other myeloid cells and hematopoietic stem cells...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773177/participation-of-selenoproteins-localized-in-the-er-in-the-processes-occurring-in-this-organelle-and-in-the-regulation-of-carcinogenesis-associated-processes
#18
REVIEW
Elena Gennadyevna Varlamova
The functions performed by the ER are diverse: synthesis of steroid hormones, synthesis of proteins for the plasma membrane, lysosomes, as well as proteins meant for exocytosis, protein folding, formation of disulfide bonds, N-linked glycosylation, etc. Selenoproteins localized in this organelle are definitely involved in the processes occurring in it, and the most common of them include participation in protein degradation, regulation of ER stress and redox metabolism. ER stress has been registered in many types of cancer cells...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29772664/the-cholinergic-anti-inflammatory-response-and-the-role-of-macrophages-in-hiv-induced-inflammation
#19
REVIEW
Manuel Delgado-Vélez, José A Lasalde-Dominicci
Macrophages are phagocytic immune cells that protect the body from foreign invaders and actively support the immune response by releasing anti- and proinflammatory cytokines. A seminal finding revolutionized the way macrophages are seen. The expression of the neuronal alpha7 nicotinic acetylcholine receptor (α7-nAChR) in macrophages led to the establishment of the cholinergic anti-inflammatory response (CAR) in which the activation of this receptor inactivates macrophage production of proinflammatory cytokines...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772353/cardiac-profile-of-chimeric-antigen-receptor-car-t-cell-therapy-in-children-a-single-institution-experience
#20
Danielle Burstein, Shannon Maude, Stephen Grupp, Heather Griffis, Joseph Rossano, Kimberly Lin
BACKGROUND: Immunotherapy with chimeric antigen receptor (CAR)-modified T-cells targeting CD19 for pediatric acute lymphoblastic leukemia (ALL) has demonstrated significant efficacy. The principle toxicity is cytokine release syndrome with resultant hypotension. However, the spectrum of cardiovascular effects associated with CAR T-cell therapy has not been systematically evaluated. METHODS: We reviewed all patients who received CD19-directed CAR T-cells at the Children's Hospital of Philadelphia between April 2012 and September 2016...
May 14, 2018: Biology of Blood and Marrow Transplantation
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