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https://www.readbyqxmd.com/read/27920696/sequential-therapy-with-nivolumab-followed-by-ipilimumab-induces-complete-response-in-metastatic-melanoma-of-the-lung-but-with-severe-hepatotoxicities
#1
Sadanori Furudate, Taku Fujimura, Yumi Kambayashi, Takanori Hidaka, Akira Hashimoto, Setsuya Aiba
Since nivolumab significantly prolongs survival in patients with metastatic melanoma, the number of patients administered nivolumab is increasing, but only 30-40% of patients who received nivolumab monotherapy experienced objective tumor regression. Therefore, enhancing its anti-tumor immune response is of great interest to dermato-oncologists. In this report, we present a case of multiple metastatic melanomas in the lung successfully treated with nivolumab (2 mg/kg every 3 weeks for 12 weeks) followed by ipilimumab (3 mg/kg every 3 weeks for 9 weeks), but with severe liver dysfunction...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27919789/unravelling-a-p73-regulated-network-the-role-of-a-novel-p73-dependent-target-mir3158-in-cancer-cell-migration-and-invasiveness
#2
Sotiris Galtsidis, Stella Logotheti, Athanasia Pavlopoulou, Christos P Zampetidis, Georgia Papachristopoulou, Andreas Scorilas, Borek Vojtesek, Vassilis Gorgoulis, Vassilis Zoumpourlis
The transcription factor p73 is homologous to the well-known tumor-suppressor p53. The p73-regulated networks are of significant clinical interest, because they may substitute for impaired p53-regulated networks which are commonly perturbed in cancer. Herein, we aimed to characterize a p73-regulated network that mediates cell migration and restores anti-oncogenic responses in p53-mutant cancer cells. In this study, we demonstrate that p73 regulates a network underlying cell migration, which consists of MIR34A/MIR3158/vimentin/β-catenin/lef1...
December 2, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27919710/the-transcription-factor-carbohydrate-response-element-binding-protein-chrebp-a-possible-link-between-metabolic-disease-and-cancer
#3
REVIEW
Katsumi Iizuka
Carbohydrate-response element-binding protein (ChREBP) has been identified as a transcription factor that binds to carbohydrate response element in the promoter of pyruvate kinase, liver and red blood cells. ChREBP is activated by metabolites derived from glucose and suppressed by adenosine monophosphate (AMP), ketone bodies and cyclic cAMP. ChREBP regulates gene transcription related to glucose and lipid metabolism. Findings from knockout mice and human subjects suggest that ChREBP helps to induce hepatic steatosis, dyslipidemia, and glucose intolerance...
December 2, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27918780/effect-of-a-proposed-trastuzumab-biosimilar-compared-with-trastuzumab-on-overall-response-rate-in-patients-with-erbb2-her2-positive-metastatic-breast-cancer-a-randomized-clinical-trial
#4
Hope S Rugo, Abhijit Barve, Cornelius F Waller, Miguel Hernandez-Bronchud, Jay Herson, Jinyu Yuan, Rajiv Sharma, Mark Baczkowski, Mudgal Kothekar, Subramanian Loganathan, Alexey Manikhas, Igor Bondarenko, Guzel Mukhametshina, Gia Nemsadze, Joseph D Parra, Maria Luisa T Abesamis-Tiambeng, Kakhaber Baramidze, Charuwan Akewanlop, Ihor Vynnychenko, Virote Sriuranpong, Gopichand Mamillapalli, Sirshendu Ray, Eduardo P Yanez Ruiz, Eduardo Pennella
Importance: Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)-positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy. Objective: To compare the overall response rate and assess the safety of a proposed trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior treatment for ERBB2-positive metastatic breast cancer...
December 1, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27918764/effect-of-fluorouracil-leucovorin-and-oxaliplatin-with-or-without-onartuzumab-in-her2-negative-met-positive-gastroesophageal-adenocarcinoma-the-metgastric-randomized-clinical-trial
#5
Manish A Shah, Yung-Jue Bang, Florian Lordick, Maria Alsina, Meng Chen, Stephen P Hack, Jean Marie Bruey, Dustin Smith, Ian McCaffery, David S Shames, See Phan, David Cunningham
Importance: Dysregulation of the mesenchymal-epithelial transition (MET) signaling pathway is associated with poor prognosis in gastroesophageal adenocarcinoma (GEC). We report results of METGastric, a phase 3 trial of the MET inhibitor onartuzumab plus standard first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, MET-positive, advanced GEC. Objective: To determine whether the addition of onartuzumab to first-line fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) improves efficacy compared with mFOLFOX6 plus placebo in HER2-negative, MET-positive GEC...
December 1, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#6
Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy, Christine G Lian
Ipilimumab (IPI) is a monoclonal antibody that targets the inhibitory CTLA4 receptor of T cells, enhancing T-cell-driven antitumor responses. IPI therapy in metastatic melanoma results in significant improvement in disease-free and overall survival, although after initial responses disease progression generally ensues. Identification of specific responses in tissue where melanoma tumor cells are subjected to IPI-driven immune attack may reveal mechanisms of treatment efficacy or resistance, permitting refinement of targeted therapeutic approaches...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27918105/resveratrol-inhibits-proliferation-invasion-and-epithelial-mesenchymal-transition-by-increasing-mir-200c-expression-in-hct-116-colorectal-cancer-cells
#7
Fatemeh Karimi Dermani, Massoud Saidijam, Razieh Amini, Ali Mahdavinezhad, Korosh Heydari, Rezvan Najafi
OBJECTIVE: Colorectal cancer (CRC) is one of the most common malignancies, associated with high rates of relapse. A notable challenge in treatment is low response rate to current therapies for advanced CRC. The miR-200c plays an essential role in tumor suppression by inhibiting epithelial-mesenchymal transition (EMT). Resveratrol, a natural compound found in red wine, reveals anti-cancer properties in several types of cancers such as CRC. The aim of current study was to evaluate the effects of resveratrol on proliferation, apoptosis and invasion of HCT-116 cells and also expression of EMT-related genes in presences or absence of miR-200c...
December 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27918099/mir-193b-mediates-cebpd-induced-cisplatin-sensitization-through-targeting-ets1-and-cyclin-d1-in-human-urothelial-carcinoma-cells
#8
Siao-Ren Lin, Hsin-Chih Yeh, Wei-Jan Wang, Hung-Lung Ke, Hui-Hui Lin, Wei-Chi Hsu, Shi-Yi Chao, Tzyh-Chyuan Hour, Wen-Jeng Wu, Yeong-Shiau Pu, A-Mei Huang
Transcription factor CCAAT/enhancer-binding protein delta (CEBPD) plays multiple roles in tumor progression. Studies have demonstrated that cisplatin (CDDP) induced CEBPD expression and had led to chemotherapeutic drug resistance. However, the underlying molecular mechanisms of CDDP-regulated CEBPD expression and its relevant roles in CDDP responses remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Abnormal miRNAs expression is associated with tumor progression...
December 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27917949/intravenous-hmscs-ameliorate-acute-pancreatitis-in-mice-via-secretion-of-tumor-necrosis-factor-%C3%AE-stimulated-gene-protein-6
#9
Zhigang He, Jie Hua, Daohai Qian, Jian Gong, Shengping Lin, Chenglei Xu, Ge Wei, Hongbo Meng, Tingsong Yang, Bo Zhou, Zhenshun Song
The administration of mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs) to enhance tissue repair is currently undergoing clinical trials. Some studies, including our previous work, have also revealed the beneficial effect of MSCs in severe acute pancreatitis (SAP); however, their mechanisms or mode of action remain controversial. In this study, we demonstrated that intravenously (i.v.)-administered human MSCs (hMSCs) remarkably promoted recovery from experimental SAP without significant engraftment of hMSCs in the damaged pancreas...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917631/-15-years-experience-with-biological-therapy-of-inflammatory-rheumatic-diseases-in-czech-national-register-attra
#10
Karel Pavelka, Liliana Šedová, Karel Hejduk, Ladislav Dušek
The publication is summarizing application of biological DMARDs in autoimmune inflammatory rheumatic diseases.Up to now conventional therapy, which for example in rheumatoid arthritis was application of methotrexate (MTx) in combination with glucocorticoids, was effective, but the remission as a target was achieved in small proportion of patients and also there was little effect on structural progression of diseases. Biological therapy was great advance because response was achieved in ¾ patients who failed MTx...
2016: Casopís Lékar̆ů C̆eských
https://www.readbyqxmd.com/read/27917371/hijacker-of-the-antitumor-immune-response-autophagy-is-showing-its-worst-facet
#11
REVIEW
Elodie Viry, Muhammad Zaeem Noman, Tsolère Arakelian, Audrey Lequeux, Salem Chouaib, Guy Berchem, Etienne Moussay, Jérôme Paggetti, Bassam Janji
Macroautophagy (hereafter referred to as autophagy) is a housekeeping process constitutively executed at basal level in all cells to promote cellular homeostasis by regulating organelle and protein turnover. However, autophagy deregulation caused by several stress factors, such as hypoxia, is prevalent in many cancers. It is now well established that autophagy can act as tumor suppressor or tumor promoter depending on tumor type, stage, and genetic context. In developed tumors, autophagy promotes the survival of cancer cells and therefore operates as a cell resistance mechanism...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27917263/changes-in-cellular-proliferation-and-plasma-products-are-associated-with-liver-failure
#12
Juliana Gil Melgaço, Frederico Marianetti Soriani, Pedro Henrique Ferreira Sucupira, Leonardo Assaf Pinheiro, Yasmine Rangel Vieira, Jaqueline Mendes de Oliveira, Lia Laura Lewis-Ximenez, Cristina Carvalho Vianna Araújo, Lúcio Filgueiras Pacheco-Moreira, Gustavo Batista Menezes, Oswaldo Gonçalves Cruz, Claudia Lamarca Vitral, Marcelo Alves Pinto
AIM: To study the differences in immune response and cytokine profile between acute liver failure and self-limited acute hepatitis. METHODS: Forty-six patients with self-limited acute hepatitis (AH), sixteen patients with acute liver failure (ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR...
November 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27916138/alcohol-exposure-differentially-effects-anti-tumor-immunity-in-females-by-altering-dendritic-cell-function
#13
Matthew G Thompson, Flor Navarro, Lennox Chitsike, Luis Ramirez, Elizabeth J Kovacs, Stephanie K Watkins
Dendritic cells (DCs) are a critical component of anti-tumor immunity due to their ability to induce a robust immune response to antigen (Ag). Alcohol was previously shown to reduce DC ability to present foreign Ag and promote pro-inflammatory responses in situations of infection and trauma. However the impact of alcohol exposure on generation of an anti-tumor response, especially in the context of generation of an immune vaccine has not been examined. In the clinic, DC vaccines are typically generated from autologous blood, therefore prior exposure to substances such as alcohol may be a critical factor to consider regarding the effectiveness in generating an immune response...
December 2016: Alcohol
https://www.readbyqxmd.com/read/27915436/bone-marrow-produces-sufficient-alloreactive-natural-killer-nk-cells-in-vivo-to-cure-mice-from-subcutaneously-and-intravascularly-injected-4t1-breast-cancer
#14
Michel van Gelder, Ariane Vanclée, Catharina H M J van Elssen, Pierre Hupperets, Lotte Wieten, Gerard M Bos
PURPOSE: Administration of 5 million alloreactive natural killer (NK) cells after low-dose chemo-irradiation cured mice of 4T1 breast cancer, supposedly dose dependent. We now explored the efficacy of bone marrow as alternative in vivo source of NK cells for anti-breast cancer treatment, as methods for in vitro clinical scale NK cell expansion are still in developmental phases. METHODS: Progression-free survival (PFS) after treatment with different doses of spleen-derived alloreactive NK cells to 4T1-bearing Balb/c mice was measured to determine a dose-response relation...
December 3, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27915154/lipopolysaccharides-stimulated-macrophage-products-enhance-withaferin-a-induced-apoptosis-via-activation-of-caspases-and-inhibition-of-nf-%C3%AE%C2%BAb-pathway-in-human-cancer-cells
#15
Liang Piao, Zhao Canguo, Lu Wenjie, Cheng Xiaoli, Shi Wenli, Lu Li
Macrophages, as a major cellular component in tumor microenvironment, play an important role in tumor progression. However, their roles in modulation of cytotoxic chemotherapy are still not fully understood. Here, we investigated the influence of Lipoplysaccharides (LPS)-stimulated macrophage products (LSMP) on Withaferin A (WA), a natural compound that derived from the medicinal plant Withania somnifera, as an antitumor agent in human breast cancer cells MDA-MB-231 and prostate cancer cells PC-3. Our results revealed that LSMP may enhance WA-induced apoptosis in both cell lines, the underlying mechanisms of which are closely associated with activation of caspase-8, -9 and -3, cleavage of poly ADP-ribose polymerase (PARP), as well as specifically inhibiting the translocation of nuclear factor-κB (NF-κB) and down-regulation of anti-apoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and inhibitor of apoptosis protein (cIAP1/2)...
December 1, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27914809/actein-enhances-trail-effects-on-suppressing-gastric-cancer-progression-by-activating-p53-caspase-3-signaling
#16
Zhi-Chao Yang, Ji Ma
Actein (ACT), isolated from the rthizomes of Cimicifuga foetida, is a triterpene glycoside, showing inhibitory role in breast cancer cells. However, the effects of ACT treatment on gastric cancer have little been known. Thus, the study is conducted to explore the in vitro and in vivo role of ACT in gastric cancer. And the interactions between ACT and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were investigated in gastric cancer cells. A synergistic effect of ACT and TRAIL combination on apoptosis induction in gastric cancer cells was observed...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27914453/myeloid-derived-suppressor-cells-and-proinflammatory-cytokines-as-targets-for-cancer-therapy
#17
REVIEW
K-S N Atretkhany, M S Drutskaya
Myeloid-derived suppressor cells represent a heterogeneous population of immature myeloid cells. Under normal conditions, these cells differentiate into macrophages, dendritic cells, and granulocytes. However, in pathological states such as inflammation, infection, or tumor growth, there is an arrest of their differentiation that results in the accumulation of immature myeloid cells in the organism. In addition, these cells acquire a suppressor phenotype, expressing anti-inflammatory cytokines and reactive oxygen and nitrogen species, and suppress T-cell immune response...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27914308/regulation-of-t-helper-cell-differentiation-by-e3-ubiquitin-ligases-and-deubiquitinating-enzymes
#18
REVIEW
Si-Fa Gao, Bo Zhong, Dandan Lin
CD4 T cells are essential components of adaptive immunity and play a critical role in anti-pathogenic or anti-tumor responses as well as autoimmune and allergic diseases. Naive CD4 T cells differentiate into distinct subsets of T helper (Th) cells by various signals including TCR, costimulatory and cytokine signals. Accumulating evidence suggests that these signaling pathways are critically regulated by ubiquitination and deubiquitination, two reversible posttranslational modifications mediated by E3 ubiquitin ligases and deubiquitinating enzymes (DUBs), respectively...
November 30, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27914269/targeted-hydroxyethyl-starch-prodrug-for-inhibiting-the-growth-and-metastasis-of-prostate-cancer
#19
Kaidong Zhao, Di Li, Weiguo Xu, Jianxun Ding, Weiqian Jiang, Mingqiang Li, Chunxi Wang, Xuesi Chen
Prostate cancer is one of the most prevalent malignancies among men. Although chemotherapy has been an effective therapeutic approach for treating metastatic prostate cancer, serious undesired side effects have hampered its wide application clinically. In this work, a pH-responsive LHRH-conjugated hydroxyethyl starch-doxorubicin (HES-DOX/LHRH) prodrug was facilely synthesized by conjugating oxidized HES (HES-CHO) with DOX and LHRH through an acid-sensitive Schiff base bond. The resulting prodrug spontaneously self-assembled into nanoscopic micelle with a radius of about 55 nm in an aqueous environment...
November 23, 2016: Biomaterials
https://www.readbyqxmd.com/read/27913835/preventive-dna-vaccination-against-cea-expressing-tumors-with-anti-idiotypic-scfv6-c4-dna-in-cea-expressing-transgenic-mice
#20
Priscila M A Denapoli, Bianca F Zanetti, Adara A Dos Santos, Jane Z de Moraes, Sang W Han
Carcinoembryonic antigen (CEA) is expressed during embryonic life and in low level during adult life. Consequently, the CEA is recognized by the immune system as a self-antigen and thus CEA-expressing tumors are tolerated. Previously, we constructed a single chain variable fragment using the 6.C4 (scFv6.C4) hybridoma cell line, which gave rise to antibodies able to recognize CEA when C57/Bl6 mice were immunized. Here, the scFv6.C4 ability to prevent the CEA-expressing tumor growth was assessed in CEA-expressing transgenic mice CEA2682...
December 2, 2016: Cancer Immunology, Immunotherapy: CII
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