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Blog of Signaling Pathways

Expression and activity of Sirtuins

5284 views | Nov 15 2011

Sirtuins are a class of proteins that possess either histone deacetylase or mono-ribosyltransferase activity, and the activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD+). Until now, seven members have been identified as sirtuin 1 (SIRT1) through SIRT 7. Of which, is considered to be one of the determining factors in longevity induced by calorie restriction. [Read the Full Post]

JNK, a potential therapeutic target for the treatment of nephrotoxicity

3365 views | Nov 14 2011

Nephrotoxicity is a poisonous effect of some substances, including toxic chemicals and medication, on the kidneys, and cyclosporine (CsA) nephrotoxicity is one kind of nephrotoxicity. It is reported that the epithelial to mesenchymal transition(EMT) is an important mechanism contributing to the pathogenesis of cyclosporine (CsA) nephrotoxicity by promoting the generation of myofibroblasts. Some studies suggested that he endoplasmic reticulum (ER) stress as a potential mechanism may participate in the modulation of tubular cell plasticity in CsA-induced EPCs[1]. However, the precise mechanisms have not been known. [Read the Full Post]

The antifungi activity of DNA topoisomerase inhibitors

3869 views | Nov 10 2011

Fungal infections represent the invasion of tissues by one or more species of fungi, such as Aspergillus and yeasts. Some fungal infections will trigger the body’s immune system, cause inflammation and tissue damage, and even lead to serious lung, blood (septicemia) or systemic diseases. [Read the Full Post]

Co-treatment of PI3K inhibitors with temsirolimus, an optimized therapy in the treatment of cancers related to mTORs.

2523 views | Nov 08 2011

The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that mediates cell growth, cell proliferation, cell motility, cell survival, gene transcription, and protein synthesis. In many human cancers, particularly those with loss of the tumor suppressor PTEN, dysregulation of the mTOR signaling can be observed, and activation of mTORs have shown the significant sensitivity to rapamycin. [Read the Full Post]

Roles of PI3Ks in tumors

2693 views | Nov 07 2011

Phosphatidylinositol 3-kinases (PI3Ks) are a family of enzymes involved in a variety of cellular functions including cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, and the effects are considered to be implemented through regulating the activities of a broad range of downstream molecular effectors. Since phosphorylation of PI3K-AKT-mTOR inhibits the activity of proapoptotic members while activating anti-apoptotic members, and is considered to play an important role in cancer stem cell self-renewal and resistance to chemotherapy or radiotherapy. [Read the Full Post]

Survivin, the novel target for the treatment of fibrotic disease

5333 views | Nov 06 2011

A fibroblast is a type of mesenchymal cells that synthesize the extracellular matrix(ECM) and collagen, and plays a key role in wound healing by differentiating into alpha-smooth muscle actin expressing myofibroblasts. At last, the normal wound repair progress following injury requires the elimination of myofibroblasts by apoptosis. However, in abnormal state, this excessive ECM can result in the progressive destruction of tissue architecture and lead to impaired organ function. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive form of lung disease caused by fibrosis of the lungs. [Read the Full Post]

The roles of p53 in hematopoietic stem cell rate

3386 views | Nov 03 2011

At present, p53 is the star gene of the cancer studies, since more than half of cancer development and progression are reported to be related to the p53 mutation. p53 is a tumor suppressor protein, and is originally isolated as a cellular partner of simian virus 40(SV-40)-derived tumor antigens[1]. p53 has regulated several signaling pathways involved in the cell’s response to stress, and plays a role in apoptosis, genomic stability, senescence, inducing cell-cycle arrest and inhibition of angiogenesis. [Read the Full Post]

Raf kinases, the excellent molecular targets for anticancer therapy

3181 views | Oct 31 2011

Raf kinases are a family of three serine/threonine-specific protein kinases that are related to retroviral oncogenes. Raf kinases mainly contain three mammalian RAF proteins (A, B and CRAF) and participate in the RAS-RAF-MEK-ERK signal pathways. Of which, B-Raf is the family member most easily activated by Ras, and the kinase activity of B-Raf is higher than that of C-Raf and, likely, A-Raf. Thus, the frequent mutational activation of BRAF is often observed in human tumors, but not CRAF or ARAF. [Read the Full Post]

Roles of PIM serine/threonine kinases in cancers

6599 views | Oct 27 2011

The Pim family of Ser/Thr kinases has been first identified in murine Moloney leukemia virus induced lymphomas, and is composed of three isoforms, Pim-1, Pim-2 and Pim-3. The following studies show that Pims are constitutively activated in many cancers. Of which, Pim-1 and Pim-2 were found to show the elevated levels mostly in hematologic malignancies and prostate cancer, while increased Pim-3 expression was mainly observed in different solid tumors. [Read the Full Post]

The combination of VE-465 and vincristine, the potential therapy for leukemia

6951 views | Oct 25 2011

Leukemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of white blood cells, and studies on the treatment of the disease have been carried out for many years. At present, a variety of small-molecule agents targeting specific leukemogenetic molecules have been used in preclinical or clinical treatment of leukemia. For example, BCR/ABL kinase inhibitors, including imatinib, nilotinib and dasatinib have shown the effective treatment against BCR/ABL-positive leukemia. However, novel agents and therapy may be still needed, since monotherapy shows only limited clinical efficacy. [Read the Full Post]

Roles of Hsp90 in wound healing and cancer

5063 views | Oct 24 2011

Wound healing is an intricate process in which the skin (or another organ-tissue) repairs itself after injury. At present, local growth factors are considered to be the driving force for wound healing and only recombinant human platelet-derived growth factor-BB (PDGF-BB) has been approved by US FDA for topical treatment of diabetic ulcers. However, the use of PDGF-BB in clinical trials has been limited for its modest efficacy, high cost and risk of causing cancer. Thus, novel treatment for wound healing is needed to be explored. [Read the Full Post]

The regulation of sphingosine-1-phosphate metabolism

4037 views | Oct 20 2011

Sphingosine-1-phosphate (S1P) is a signaling sphingolipid and is also referred to as a bioactive lipid mediator. Functions of S1P are mediated by its binding to a class of G-protein coupled receptors of the S1P and Lysophospholipid (LPA) receptor families, and regulate a variety of cell signaling pathways, including cell growth, differentiation, survival, and apoptosis. Many factors in the metabolism pathway of S1P have been considered as potential targets for therapeutic intervention, including the inhibition of S1P activation of the G-protein coupled receptors. [Read the Full Post]

The roles of Midkine/Alk signaling in sympathetic neurons physiologically and pathologically

3996 views | Oct 18 2011

Neuroblastoma(NB) is the most common extracranial solid cancer that arises in immature nerve cells, and thus often occurs in childhood and infancy, with an incidence of about 650 new cases per year in US. Some evidences suggested that disposition and process of NB may be associated to proliferation of immature sympathetic neurons regulated by some transcription factors. [Read the Full Post]

Sorafenib, a potential therapy for Chronic lymphocytic leukemia patients

2553 views | Oct 13 2011

Chronic lymphocytic leukemia (CLL) is a common leukemia which causes a slow increase in white blood cells called B lymphocytes, or B cells. This cancer mostly affects adults, around age 70, and leads to approximately 5000 deaths annually. The frontline therapy for CLL mainly use several chemotherapy drugs alone or in combination, such as Fludarabine, chlorambucil, cyclophosphamide, and rituximab. Besides, bone marrow or stem cell transplantation may be used in younger patients with advanced or high-risk CLL. [Read the Full Post]

HBO2 may produce great benefits to radiation necrosis populations

1606 views | Oct 11 2011

Radiation tissues injury (radiation necrosis) is a "side effect" of radiation therapy for a tumor and can develop months or years after treatment with radiation. Especially in the irradiated area, destruction of nutrient blood vessels can result in local ulceration, destruction of bone and bleeding. This damage inhibits the ability of the irradiated tissue to repair itself, and a radiation necrosis wound can gradually affect and involve surrounding tissue. Affected patients may become socially isolated and are suffered from depression, or nutritional deficiency. [Read the Full Post]

Enzastaurin, as the inhibitor of PKC, may be a novel PNC medical therapy

4421 views | Sep 29 2011

Pancreatic cancer is the fourth most common cause of cancer death both in the United States. Regarding the pathology, pancreatic cancer mainly includes exocrine pancreas cancers, pancreatic cystic neoplasms and endocrine pancreatic cancers. Pancreatic neuroendocrine cancers (PNC) account for less than 3% of pancreatic tumors and the main treatments are surgery, hormone therapy, chemotherapy and so on at this stage. However, It is still needed to search for effective treatments for PNC, and understand the molecular pathways regulating neuroendocrine tumor cell proliferation. [Read the Full Post]

S6K and PDK1 modulate neuronal size specification

5924 views | Sep 22 2011

Synapse is located in the nervous system and a structure that passes an electrical or chemical signalfrom a neuron to another cell. The presynaptic terminal is a specialized area within the axon of the presynaptic cell that contains neurotransmitters enclosed in small membrane-bound spheres called synaptic vesicles. Active zones is a region that synaptic vesicles are docked at the presynaptic plasma membrane. [Read the Full Post]

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

11383 views | Sep 20 2011

Ovarian cancer is a cancerous growth arising from the ovary, and remains the leading cause of death from gynecological cancer, accounting for more than 140,000 deaths per year worldwide. The risk of developing ovarian cancer appears to be affected by several factors, and 10% of ovarian cancer patients have a family history of the disease. Certain genes defects (BRCA1 and BRCA2) are considered to be responsible for a small number of ovarian cancer cases. [Read the Full Post]

FLT3 ligand enhances efficacy of RNA Vaccines in cancer therapy

4144 views | Sep 14 2011

Vaccines work on the principle of promote the immune system to recognize an invader and attack it more quickly, before it can do any harm. Recently, self-replicating RNA vaccines have emerged as an effective and safe approach to induce antitumor immunity. Self-replicating RNA can replicate in a diverse range of cell types, allows the expression of the Ag of interest at high levels, and eventually causes lysis of transfected cells. [Read the Full Post]

Alexander V. Sirotkin “The role of protein kinases in control of ovarian functions”

2723 views | Sep 13 2011

Control of basic physiological processes including reproduction requires multilevel signaling system, which includes hormones, growth factors and related molecules, their receptors and binding proteins, whose alter expression of target genes via protein kinases (PKs) and transcription factors. These signaling substances can control reproductive processes via production, binding and metabolism of regulators of cell cycle, apoptosis, secretory activity, differentiation and oogenesis. [Read the Full Post]