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Advances in Biological Regulation

Ifeoluwa Adewumi, Camila López, James R Davie
The mitogen- and stress-activated protein kinases activated by the extracellular-signal-regulated kinase 1/2 and/or stress-activated protein kinase 2/p38 mitogen-activated protein kinase pathways are recruited to the regulatory region of a subset of genes termed immediate-early genes, often leading to their induction. These genes, many of which code for transcription factors, have been directly linked to the phenotypic events in carcinogenesis. In this paper, we focus on the mitogen- and stress-activated protein kinases; their discovery, activation, H3 phosphorylation and recent discoveries in their roles in cancer...
September 17, 2018: Advances in Biological Regulation
Gabor J Tigyi, Junming Yue, Derek D Norman, Erzsebet Szabo, Andrea Balogh, Louisa Balazs, Guannan Zhao, Sue Chin Lee
The lipid mediator lysophosphatidic acid (LPA) in biological fluids is primarily produced by cleavage of lysophospholipids by the lysophospholipase D enzyme Autotaxin (ATX). LPA has been identified and abundantly detected in the culture medium of various cancer cell types, tumor effusates, and ascites fluid of cancer patients. Our current understanding of the physiological role of LPA established its role in fundamental biological responses that include cell proliferation, metabolism, neuronal differentiation, angiogenesis, cell migration, hematopoiesis, inflammation, immunity, wound healing, regulation of cell excitability, and the promotion of cell survival by protecting against apoptotic death...
September 16, 2018: Advances in Biological Regulation
Yoshiteru Kagawa, Banlanjo A Umaru, Islam Ariful, Subrata Kumar Shil, Hirofumi Miyazaki, Yui Yamamoto, Masaki Ogata, Yuji Owada
Lipids are major molecules for the function of organisms and are involved in the pathophysiology of various diseases. Fatty acids (FAs) signaling and their metabolism are some of the most important pathways in tumor development, as lipids serve as energetic sources during carcinogenesis. Fatty acid binding proteins (FABPs) facilitate FAs transport to different cell organelles, modulating their metabolism along with mediating other physiological activities. FABP7, brain-typed FABP, is thought to be an important molecule for cell proliferation in healthy as well as diseased organisms...
September 15, 2018: Advances in Biological Regulation
Peter P Ruvolo
The microenvironment within the bone marrow (BM) contains support cells that promote leukemia cell survival and suppress host anti-tumor defenses. Galectins are a family of beta-galactoside binding proteins that are critical components in the tumor microenvironment. Galectin 1 (LGALS1) and Galectin 3 (LGALS3) as regulators of RAS signaling intracellularly and as inhibitors of immune cells extracellularly are perhaps the best studied members for their role in leukemia biology. Interest in Galectin 9 (LGALS9) is growing as this galectin has been identified as an immune checkpoint molecule...
September 12, 2018: Advances in Biological Regulation
Caitlyn E Bowman, Michael J Wolfgang
Malonyl-CoA is a central metabolite in fatty acid biochemistry. It is the rate-determining intermediate in fatty acid synthesis but is also an allosteric inhibitor of the rate-setting step in mitochondrial long-chain fatty acid oxidation. While these canonical cytoplasmic roles of malonyl-CoA have been well described, malonyl-CoA can also be generated within the mitochondrial matrix by an alternative pathway: the ATP-dependent ligation of malonate to Coenzyme A by the malonyl-CoA synthetase ACSF3. Malonate, a competitive inhibitor of succinate dehydrogenase of the TCA cycle, is a potent inhibitor of mitochondrial respiration...
September 5, 2018: Advances in Biological Regulation
Jamie L Sturgill
Asthma is defined as a chronic inflammatory condition in the lung and is characterized by episodic shortness of breath with expiratory wheezing and cough. Asthma is a serious public health concern globally with an estimated incidence over 300 million. Asthma is a complex disease in that it manifests as disease of gene and environmental interactions. Sphingolipids are a unique class of lipids involved in a host of biological functions ranging from serving as key cellular membrane lipids to acting as critical signaling molecules...
September 5, 2018: Advances in Biological Regulation
Deanna Davis, Muthukumar Kannan, Binks Wattenberg
Sphingolipids comprise a diverse family of lipids that perform multiple functions in both structure of cellular membranes and intra- and inter-cellular signaling. The diversity of this family is generated by an array of enzymes that produce individual classes and molecular species of family members and enzymes which catabolize those lipids for recycling pathways. However, all of these lipids begin their lives with a single step, the condensation of an amino acid, almost always serine, and a fatty acyl-CoA, almost always the 16-carbon, saturated fatty acid, palmitate...
August 31, 2018: Advances in Biological Regulation
Jason Newton, Sheldon Milstien, Sarah Spiegel
Niemann-Pick type C (NPC) disease is a lysosomal storage disorder resulting from mutations in either the NPC1 (95%) or NPC2 (5%) genes. NPC typically presents in childhood with visceral lipid accumulation and complex progressive neurodegeneration characterized by cerebellar ataxia, dysphagia, and dementia, resulting in a shortened lifespan. While cholesterol is widely acknowledged as the principal storage lipid in NPC, multiple species of sphingolipids accumulate as well. This accumulation of sphingolipids led to the initial assumption that NPC disease was caused by a deficiency in a sphingolipid catabolism enzyme, similar to sphingomyelinase deficiencies with which it shares a family name...
August 28, 2018: Advances in Biological Regulation
Stephen L Abrams, Kvin Lertpiriyapong, Li V Yang, Alberto M Martelli, Lucio Cocco, Stefano Ratti, Marco Falasca, Ramiro M Murata, Pedro L Rosalen, Paolo Lombardi, Massimo Libra, Saverio Candido, Giuseppe Montalto, Melchiorre Cervello, Linda S Steelman, James A McCubrey
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5-10%. Mutations at the TP53 gene are readily detected in pancreatic tumors isolated from PDAC patients. We have investigated the effects of restoration of wild-type (WT) TP53 activity on the sensitivity of pancreatic cancer cells to: chemotherapy, targeted therapy, as well as, nutraceuticals. Upon introduction of the WT-TP53 gene into the MIA-PaCa-2 pancreatic cancer cell line, the sensitivity to drugs used to treat pancreatic cancer cells such as: gemcitabine, fluorouracil (5FU), cisplatin, irinotecan, oxaliplatin, and paclitaxel increased significantly...
August 2018: Advances in Biological Regulation
Kenneth Kaushansky, Huichun Zhan
Each day the adult human produces 4 × 1011 red blood cells, 1 × 1011 white blood cells and 1 × 1011 platelets, levels of production which can increase 10-20 fold in times of heightened demand. Hematopoiesis, or the formation of the ten different types of blood and marrow cells, is a complex process involving hematopoietic stem cells (HSCs), cytokine growth factors and cell surface adhesion molecules, and both specific and ubiquitous transcription factors. The marrow micro-environmental niche is defined as the site at which HSCs reside and are nurtured, receiving the signals that lead to their survival, replication and/or differentiation...
August 2018: Advances in Biological Regulation
D Drulis-Fajdasz, D Rakus, J R Wiśniewski, J A McCubrey, A Gizak
Glycogen synthase kinase-3 (GSK-3) is a constitutively active kinase, involved in regulation of multiple physiological processes. In brain, changes in GSK-3 signaling are related to neurodegenerative issues, including Alzheimer's disease. Due to the wide range of GSK-3 cellular targets, a therapeutic use of the enzyme inhibitors entails significant risk of side effects. Thus, altering the ratio of specific pool of GSK-3 or specific substrates instead of changing the global activity of GSK-3 in brains might be a more appropriate strategy...
August 2018: Advances in Biological Regulation
William H Chappell, Saverio Candido, Stephen L Abrams, Suzanne Russo, Roger Ove, Alberto M Martelli, Lucio Cocco, Giulia Ramazzotti, Melchiorre Cervello, Giuseppe Montalto, Linda S Steelman, Xiaohong Leng, Ralph B Arlinghaus, Massimo Libra, James A McCubrey
Neutrophil gelatinase-associated lipocalin (NGAL a.k.a lipocalin 2, lnc2) is a secreted protein which can form a complex with matrix metalloproteinase-9 (MMP9). This MMP9/NGAL complex has been associated with metastasis. MMP9 and NGAL are detected in the urine of patients afflicted with many different types of cancer, including prostate cancer. The effects of p53, NF-κB and the androgen receptor (AR) on the expression of NGAL was examined in four prostate cancer cell lines. Prostate cancer cell lines that are AR negative and expressed either mutant or no p53 (DU145 and PC3) displayed higher levels of NGAL expression compared to the prostate cancer cell lines (LNCaP and 22Rv-1) which are AR positive and express wild type (WT) p53...
August 2018: Advances in Biological Regulation
Sayyed K Zaidi, Andrew J Fritz, Kirsten M Tracy, Jonathan A Gordon, Coralee E Tye, Joseph Boyd, Andre J Van Wijnen, Jeffrey A Nickerson, Antony N Imbalzano, Jane B Lian, Janet L Stein, Gary S Stein
Nuclear organization is functionally linked to genetic and epigenetic regulation of gene expression for biological control and is modified in cancer. Nuclear organization supports cell growth and phenotypic properties of normal and cancer cells by facilitating physiologically responsive interactions of chromosomes, genes and regulatory complexes at dynamic three-dimensional microenvironments. We will review nuclear structure/function relationships that include: 1. Epigenetic bookmarking of genes by phenotypic transcription factors to control fidelity and plasticity of gene expression as cells enter and exit mitosis; 2...
August 2018: Advances in Biological Regulation
Pann-Ghill Suh
No abstract text is available yet for this article.
May 2018: Advances in Biological Regulation
Hideki Hasegawa, Kaori Sano, Akira Ainai, Tadaki Suzuki
Adult T-cell leukemia-lymphoma (ATL) is a refractory T-cell malignancy caused by infection of human T-cell leukemia virus type I (HTLV-I). Although the pathogenesis of ATL remains unclear, HTLV-1 oncoprotein Tax plays an important role in pathogenesis (Matsuoka, 2003; Jeang et al., 2004). Chemotherapy resistance of ATL leads the poor prognosis of this disease. In order to understand the pathogenesis and establish an animal model useful for therapy attempts, we have generated HTLV-1 Tax transgenic mice using the Lck proximal promoter to restrict the Tax expression in T-cells...
May 2018: Advances in Biological Regulation
Jessika Bertacchini, Chiara Frasson, Francesca Chiarini, Daniele D'Avella, Benedetta Accordi, Laura Anselmi, Patrizia Barozzi, Fabio Forghieri, Mario Luppi, Alberto M Martelli, Giuseppe Basso, Saki Najmaldin, Abbas Khosravi, Fakher Rahim, Sandra Marmiroli
A main cause of treatment failure for AML patients is resistance to chemotherapy. Survival of AML cells may depend on mechanisms that elude conventional drugs action and/or on the presence of leukemia initiating cells at diagnosis, and their persistence after therapy. MDR1 gene is an ATP-dependent drug efflux pump known to be a risk factor for the emergence of resistance, when combined to unstable cytogenetic profile of AML patients. In the present study, we analyzed the sensitivity to conventional chemotherapeutic drugs of 26 samples of primary blasts collected from AML patients at diagnosis...
May 2018: Advances in Biological Regulation
Saverio Candido, Stephen L Abrams, Linda Steelman, Kvin Lertpiriyapong, Alberto M Martelli, Lucio Cocco, Stefano Ratti, Matilde Y Follo, Ramiro M Murata, Pedro L Rosalen, Paolo Lombardi, Giuseppe Montalto, Melchiorre Cervello, Agnieszka Gizak, Dariusz Rakus, Pann-Gill Suh, Massimo Libra, James A McCubrey
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5-10% after diagnosis and treatment. Pancreatic cancer has been associated with type II diabetes as the frequency of recently diagnosed diabetics that develop pancreatic cancer within a 10-year period of initial diagnosis of diabetes in increased in comparison to non-diabetic patients. Metformin is a very frequently prescribed drug used to treat type II diabetes...
May 2018: Advances in Biological Regulation
Suyong Choi, Xander Houdek, Richard A Anderson
Phosphatidylinositol phosphate kinases (PIPKs) generate a lipid messenger phosphatidylinositol 4,5-bisphosphate (PI4,5P2 ) that controls essentially all aspects of cellular functions. PI4,5P2 rapidly diffuses in the membrane of the lipid bilayer and does not greatly change in membrane or cellular content, and thus PI4,5P2 generation by PIPKs is tightly linked to its usage in subcellular compartments. Based on this verity, recent study of PI4,5P2 signal transduction has been focused on investigations of individual PIPKs and their underlying molecular regulation of cellular processes...
May 2018: Advances in Biological Regulation
Sang-Kyu Lee, Jeong-Ha Hwang, Kang-Yell Choi
Cancer development is usually driven by multiple genetic and molecular alterations rather than by a single defect. In the human colorectal cancer (CRC), series of mutations of genes are involved in the different stages of tumorigenesis. For example, adenomatous polyposis coli (APC) and KRAS mutations have been known to play roles in the initiation and progression of the tumorigenesis, respectively. However, many studies indicate that mutations of these two genes, which play roles in the Wnt/β-catenin and RAS-extra-cellular signal regulated kinase (ERK) pathways, respectively, cooperatively interact in the tumorigenesis in several different cancer types including CRC...
May 2018: Advances in Biological Regulation
Kanae Echizen, Hiroko Oshima, Mizuho Nakayama, Masanobu Oshima
Accumulating evidence has indicated that the inflammatory response is important for tumor promotion. However, the mechanisms underlying the induction of the inflammatory response in cancer tissues and how it promotes tumorigenesis remain poorly understood. We constructed several mouse models that develop inflammation-associated gastric and intestinal tumors and examined the in vivo mechanisms of tumorigenesis. Of note, the activation of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2 ) pathway and Toll-like receptor (TLR)/MyD88 signaling cooperatively induced the generation of an inflammatory microenvironment, which is required for early-stage tumorigenesis...
May 2018: Advances in Biological Regulation
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