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Blog of Signaling Pathways

Cyclopamine: from cyclops lambs to cancer treatment

148 views | Mar 01 2019

Lee ST et al. showed inhibitors of the Hh signaling pathway, including cyclopamine derivatives, have been targeted as potential treatments for certain cancers and other diseases associated with the Hh signaling pathway. [Read the Full Post]

Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice

124 views | Feb 28 2019

Guo J et al. found that Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans. [Read the Full Post]

ΔNp63 drives metastasis in breast cancer cells via PI3K/CD44v6 axis

141 views | Feb 28 2019

Di Franco S et al. found that tumor microenvironmental cytokines significantly contribute to the establishment of breast cancer cell phenotype by positively regulating ΔNp63 and CD44v6 expression. [Read the Full Post]

Inactivation of PBX3 and HOXA9 by down-regulating H3K79 methylation represses NPM1-mutated leukemic cell survival

175 views | Feb 27 2019

Zhang W et al. indicated that NPMc+ leukemic cell survival requires upregulation of PBX3 and HOXA9, and this action can be largely attenuated by a DOT1L inhibitor. [Read the Full Post]

LY2109761 inhibits metastasis and enhances chemosensitivity in osteosarcoma MG-63 cells

201 views | Feb 27 2019

Ren XF et al. indicated that LY2109761 suppresses OS metastasis and enhanced chemosensitivity by targeting S100A4. LY2109761 may have important implications for the development of strategies for inhibiting metastasis and overcoming OS cell resistance to chemotherapy. [Read the Full Post]

Anti-inflammatory and chondroprotective effects of the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A, in human articular chondrocytes

122 views | Feb 26 2019

Aury-Landas J et al. showed DZNep up-regulated cartilage specific genes, such as COL2A1 and SOX9, suggesting a chondroprotective effect of DZNep. DZNep exhibits anti-inflammatory effects, and regulates genes implicated in chondroprotective response in human articular chondrocytes, suggesting that inhibitors of S-adenosylmethionine-dependent methyltransferases could be effective treatments for OA. [Read the Full Post]

DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation

130 views | Feb 26 2019

Miranda TB et al. suggested that there is a homeostatic mechanism that returns the histone modifications to their "ground state" after DZNep treatment. Our data show the strong need for further development of histone methylation inhibitors. [Read the Full Post]

Microglial modulation through colony-stimulating factor-1 receptor inhibition attenuates demyelination

94 views | Feb 25 2019

Wies Mancini VSB et al. showed that BLZ945 induced a significant reduction in the number of microglia. Preventive BLZ945 treatment attenuated demyelination in the acute CPZ model, mainly in cortex and external capsule. In contrast, BLZ945 treatment in the acute CPZ model failed to protect myelin or foster remyelination in myelin-rich areas, which may respond to a loss in microglial phagocytic capacity and the consequent impairment in oligodendroglial differentiation. Preventive and therapeutic BLZ945 treatment promoted remyelination and neuroprotection in the chronic model. These results could be potentially transferred to the treatment of progressive forms of MS. [Read the Full Post]

RSL3 and Erastin differentially regulate redox signaling to promote Smac mimetic-induced cell death

127 views | Feb 25 2019

Dächert J et al. indicated that RSL3/BV6 and Erastin/BV6 differentially regulate redox signaling and cell death in ALL cells. While RSL3/BV6 cotreatment induces ferroptotic cell death, Erastin/BV6 stimulates oxidative cell death independently of iron. These findings have important implications for the therapeutic targeting of redox signaling to enhance Smac mimetic-induced cell death in ALL. [Read the Full Post]

Tanespimycin as antitumor therapy

299 views | Feb 24 2019

Dimopoulos MA et al. showed that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]

Design and molecular modeling of novel P38α MAPK inhibitors targeting breast cancer, synthesized from oxygen heterocyclic natural compounds

835 views | Feb 24 2019

Abdelhafez OM et al. indicated these promising results of cytotoxic activity and significant inhibition of p38α MAP kinase, were confirmed by exploring the effect of benzofuran derivative (18) on the apoptotic induction and cell cycle progression of MCF-7 cell line. Compound 18 induced preG1 apoptosis and cell growth arrest at G2/M phase preventing the mitotic cycle. Moreover it activated the caspase-7 which executes apoptosis. Molecular docking study was carried out using GOLD program to predict the mode of binding interaction of the synthesized compounds into the target p38α MAPK. Additionally, the physicochemical properties and ADME parameters of compound 18 were examined in silico to investigate its drug-likeness. [Read the Full Post]

Effects of cancer-associated point mutations on the structure, function, and stability of succinate dehydrogenase A

273 views | Feb 22 2019

Cao ZF et al. provided information important for understanding the molecular mechanisms of SDHA mutations in tumors. [Read the Full Post]

Crenolanib is a selective type I pan-FLT3 inhibitor

182 views | Feb 21 2019

Smith CC et al. showed that Crenolanib has significant promise for achieving deep and durable responses in FLT3-mutant AML, and may have a profound impact upon future medicinal chemistry efforts in oncology. [Read the Full Post]

Potent in vivo lung cancer Wnt signaling inhibition via cyclodextrin-LGK974 inclusion complexes

206 views | Feb 21 2019

Guimaraes PPG et al. indicated the development of these complexes enables safer and repeated oral or parenteral administration of Wnt signaling inhibitors, which hold promise for the treatment of multiple types of malignancies. [Read the Full Post]

Practice patterns and outcomes with the use of regorafenib in metastatic colorectal cancer: Results from the Regorafenib in Metastatic colorectal cancer - An Indian exploratory analysis study

338 views | Feb 19 2019

Ramaswamy A et al. indicated duration of treatment with regorafenib as an efficacy end point in this study is similar to available data from other regions as it is the side effect profile. [Read the Full Post]

The mTORC1/2 Inhibitor AZD8055 Strengthens the Efficiency of the MEK Inhibitor Trametinib to Reduce the Mcl-1/[Bim and Puma] ratio and to Sensitize Ovarian Carcinoma Cells to ABT-737

115 views | Feb 19 2019

Pétigny-Lechartier C et al. indicated the three-drug combination was also very efficient when replacing AZD8055 by the pan-Akt inhibitor MK-2206. This study thus proposes original multitargeted strategies and may have important implications for the design of novel approaches for ovarian cancer treatment. [Read the Full Post]

A natural compound, aristoyagonine, is identified as a potent bromodomain inhibitor by mid-throughput screening

176 views | Feb 18 2019

Kim YH et al. tested Brd4 inhibitors in gastric cancer cell lines, and found that aristoyagonine exerted cytotoxicity not only in I-BET-762-sensitive cancer cells, but also in I-BET-762-resistant cancer cells. This is the first paper to describe a natural compound as a Brd4 bromodomain inhibitor. [Read the Full Post]

Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial

310 views | Feb 18 2019

Bruix J et al. indicated that regorafenib is the only systemic treatment shown to provide survival benefit in HCC patients progressing on sorafenib treatment. Future trials should explore combinations of regorafenib with other systemic agents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafenib and regorafenib. [Read the Full Post]

Dual mTORC1/2 inhibition by INK-128 results in antitumor activity in preclinical models of osteosarcoma

135 views | Feb 17 2019

Jiang H et al. showed that INK-128 exerts potent anti-OS activity in vitro and in vivo. INK-128might be further investigated as a novel anti-OS agent. [Read the Full Post]

Dual mTORC1/2 inhibition by INK-128 results in antitumor activity in preclinical models of osteosarcoma

0 views | Feb 17 2019

Jiang H et al. showed that INK-128 exerts potent anti-OS activity in vitro and in vivo. INK-128might be further investigated as a novel anti-OS agent. [Read the Full Post]