Blog of Signaling Pathways

Nutlin-3a selects for cells harbouring TP53 mutations

0 views | Oct 29 2019

Kucab JE et al. suggested that including a Nutlin-3a counter-screen significantly improves the specificity and efficiency of the HIMA, whereby TP53-mutated clones are selected prior to sequencing and TP53-WT clones can be discarded. [Read the Full Post]

NVP-BKM120 inhibits colon cancer growth via FoxO3a-dependent PUMA induction

0 views | Oct 28 2019

Yang S et al. demonstrated a key role of PUMA in mediating the anticancer effects of NVP-BKM120 and suggest that PUMA could be used as an indicator of NVP-BKM120 sensitivity, and also have important implications for it clinical applications. [Read the Full Post]

TAZ promotes the proliferation and osteogenic differentiation of human periodontal ligament stem cells via the p-SMAD3

434 views | Oct 28 2019

Gu K et al. indicated that Hippo/TAZ plays a positive role inside the proliferation, stemness maintenance, and osteogenic specialization of h-PDLSCs, and the specific downstream factor of osteogenic differentiation is SMAD3. [Read the Full Post]

Nuclear localization of β-catenin and expression of target genes are associated with increased Wnt secretion in oral dysplasia

1260 views | Oct 27 2019

Reyes M et al. indicated that secretion of Wnt ligands is critical for β-catenin nuclear localization and expression of target genes in oral dysplasia. [Read the Full Post]

Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial

365 views | Oct 25 2019

Baselga J et al. showed that PI3K inhibition combined with endocrine therapy is effective in postmenopausal women with endocrine-resistant, hormone receptor-positive and HER2-negative advanced breast cancer. Use of more selective PI3K inhibitors, such as α-specific PI3K inhibitor, is warranted to further improve safety and benefit in this setting. No further studies are being pursued because of the toxicity associated with this combination. [Read the Full Post]

BKM120 induces apoptosis and inhibits tumor growth in medulloblastoma

321 views | Oct 25 2019

Zhao P et a. indicated that these findingshelp to establish a basis for clinical trials of BKM120, which could be a novel therapy for the treatment of medulloblastoma patients. [Read the Full Post]

RBBP8/CtIP suppresses P21 expression by interacting with CtBP and BRCA1 in gastric cancer

638 views | Oct 24 2019

Yu Y et al. revealed the chromatin modification role of RBBP8, which could suppress the histone acetylation level of P21 promoter by recruiting CtBP co-repressor complex to BRCA1 binding site. [Read the Full Post]

The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia

0 views | Oct 24 2019

Brumatti G et al. demonstrated antileukemic efficacy and safety of the birinapant/emricasan combination in vivo suggest that induction of necroptosis warrants clinical investigation as a therapeutic opportunity in AML. [Read the Full Post]

The PI3K inhibitor GDC-0941 enhances radiosensitization and reduces chemoresistance to temozolomide in GBM cell lines

316 views | Oct 22 2019

Shi F et al. suggested that the combination of TMZ, IR, and GDC-0941 is a promising choice for future treatments of GBM. [Read the Full Post]

Trichostatin A and 5-Aza-2'-Deoxycytidine influence the expression of cold-induced genes in Arabidopsis

673 views | Oct 22 2019

Song Y et al. showed this result will advance our understanding of plant freezing responses and may provide a helpful strategy for cold tolerance improvement in crops. [Read the Full Post]

Exogenous mesenchymal stem cells affect the function of endogenous lung stem cells (club cells) in phosgene-induced lung injury

0 views | Oct 21 2019

Ye K et al. showed that MSCs reduced the secretion of club cells. And MSCs enhanced the proliferation of club cells partly via activating the Notch signaling pathway, which promoted lung injury repair. [Read the Full Post]

The Phosphatidylinositol 3-Kinase Pathway as a Potential Therapeutic Target in Bladder Cancer

278 views | Oct 21 2019

Zeng SX et al. provided new insights into the therapeutic potential of targeting the PI3K pathway for the treatment of bladder cancer. [Read the Full Post]

Prolonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells

389 views | Oct 20 2019

Skalniak L et al. showed that although idasanutlin presents much improved activities compared to its precursor, it displays the similar weaknesses, which are limited elimination of cancer cells and the generation of p53-mutated drug-resistant subpopulations. [Read the Full Post]

The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques

481 views | Oct 20 2019

Laforge M et al. demonstrated that Q-VD-OPH injection in SIV-infected RMs may represent an adjunctive therapeutic agent to control HIV infection and delaying disease progression to AIDS. [Read the Full Post]

Dorsomorphin induces cancer cell apoptosis and sensitizes cancer cells to HSP90 and proteasome inhibitors by reducing nuclear heat shock factor 1 levels

358 views | Oct 19 2019

Li N et al. indicated that dorsomorphin is an HSF1 inhibitor. It induces cancer cell apoptosis, sensitizes cancer cells to both HSP90 and proteasome inhibitors, and suppresses HSP upregulation by these drugs, which may prevent the development of drug resistance. Hence, dorsomorphin and its derivates may serve as potential precursors for developing drugs against cancer. [Read the Full Post]

BI-2536 and BI-6727, dual Polo-like kinase/bromodomain inhibitors, effectively reactivate latent HIV-1

368 views | Oct 19 2019

Gohda J et al. found that BI-2536 synergistically activates the latent provirus in combination with SAHA, a histone deacetylase inhibitor, or the non-tumour-promoting phorbol ester prostratin. Our findings strongly suggest that BI-2536 and BI-6727 are potent LRAs for the "shock and kill" HIV-1 eradication strategy. [Read the Full Post]

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model

485 views | Oct 18 2019

Komla-Ebri D et al. demonstrated that NVP-BGJ398 corrects pathological hallmarks of ACH and support TKIs as a potential therapeutic approach for ACH. [Read the Full Post]

Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC

768 views | Oct 18 2019

Wei L et al. demonstrated that targeting PHGDH is an effective approach to overcome TKI drug resistance in HCC. [Read the Full Post]

The Herb-Drug Pharmacokinetic Interaction of 5-Fluorouracil and Its Metabolite 5-Fluoro-5,6-Dihydrouracil with a Traditional Chinese Medicine in Rats

377 views | Oct 17 2019

Liu JH et al. indicated the pharmacokinetic results confirm the safety of coadministering 5-FU with XSLJZT, and provide practical dosage information for clinical practice. [Read the Full Post]

Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma

643 views | Oct 17 2019

Javle M et al. indicated that BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population. [Read the Full Post]