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- Treatment sequencing of HR+/HER2- metastatic breast cancer (mBC) patients based on PIK3CA alteration status - A retrospective analysis of a US clinicogenomics database (Hall 1) - Sep 25, 2019 - Abstract #SABCS2019SABCS_1443;
This analysis demonstrated significant heterogeneity of treatment patterns and sequences for both the PIK3CA+ and PIK3CA- groups, which may be expected given the limited available targeted therapies for patients with PIK3CA mutations during the study period. Mutation status is known late in the course of metastatic disease and does not appear to be associated with choice of treatment at this time.
- Halaven (eribulin mesylate) / Eisai, Afinitor (everolimus) / Novartis
Identification of molecules that enhance the efficacy of eribulin in TNBC and IBC cell lines (Hall 1) - Sep 25, 2019 - Abstract #SABCS2019SABCS_1422;
We identified that PAK1, mTOR, and JNK inhibitors enhanced the anti-proliferation effects of eribulin in TNBC and IBC cell lines. Our data inform new treatment strategies with eribulin for TNBC and IBC that could lead to clinical trials of innovative combination therapy based on eribulin.
- Pik3ca status as a predictor of benefit from drugs targeting the Pi3k/akt/mtor pathway: A meta-analysis of randomized trials (Hall 1 - Poster Session 4) - Sep 25, 2019 - Abstract #SABCS2019SABCS_1393;
Benefit from drugs targeting the PI3 kinase/AKT/mTOR pathway in breast cancer appears to occur exclusively in those with PIK3CA or AKT mutations. Future trials of these drugs should be designed only in biomarker selected patients.Table
- doxorubicin hydrochloride / Generic mfg.
Efficacy of RIDRPI103, a reactive oxygen species (ROS) activated prodrug in treatment of breast cancer (Hall 1) - Sep 25, 2019 - Abstract #SABCS2019SABCS_1367;
Thus, this novel combination of the ROS-activatable PI3K inhibitor prodrug and chemotherapy provides strong justification for its continued development and future clinical trials for patients stricken with PI3K driven tumors.In other experiments, we show that a recent FDA-approved CDK4/6 inhibitor, palbociclib, sensitized ER+ breast cancer cell lines (T47D and MDA-MB-361) to RIDR-PI103 using cell viability assays. Experiments are ongoing to determine the mechanism of action of these novel drug combinations that could be potentially translated to clinic for treatment of breast cancer patients.
- Piqray (alpelisib) / Novartis, Faslodex (fulvestrant) / AstraZeneca
PIK3CA mutational analysis using cell-free DNA next-generation sequencing detects activating mutations that may be missed with targeted hot-spot testing (Hall 1 - Poster Session 4) - Sep 25, 2019 - Abstract #SABCS2019SABCS_1349;
While additional data may be needed to determine the clinical response from targeting these alterations, molecular data and case reports suggest that these less common PIK3CA mutations are viable targets for a PI3K inhibitor. Comprehensive NGS, including plasma-based cfDNA testing, should be considered to identify the full spectrum of patients who may respond to PI3K targeted therapies.
- Afinitor (everolimus) / Novartis
PI3K inhibitors restored the sensitivity to anti-estrogen drugs in endocrine therapy resistant cell lines (Hall 1 - Poster Session 6) - Sep 25, 2019 - Abstract #SABCS2019SABCS_1291;
We investigated the changes in the expression and functions of ER when endocrine-resistant cell lines, established in our laboratory, were treated with PI3K-mTOR inhibitors Methods Long-term estrogen deprivation-resistant (EDR) cell lines and fulvestrant-resistant cell lines (MFR) were established from MCF-7 cells in our previous studies...We used buparlisib (BUP, pan-class1 PI3K inhibitor) and alpelisib (ALP, ?-specific PI3K inhibitor) as PI3K inhibitors and everolimus (EVE) as an mTOR inhibitor...Conclusion PI3K inhibitor could restore the expression of ER and sensitivity to anti-estrogen drugs in endocrine therapy resistant cell line in which ER expression was lost during acquired resistant period. This restoration might be due to a histone modification (H3K27me3).
- paclitaxel / Generic mfg., alisertib (MLN8237) / Takeda
Randomized, multicenter phase II trial of weekly paclitaxel with or without the oral selective Aurora Kinase A (AURKA) inhibitor, Alisertib, in patients with ER+ HER2- metastatic breast cancer (Stars at Night Ballroom 1&2 - 3rd Level) - Sep 25, 2019 - Abstract #SABCS2019SABCS_1131;
Addition of oral A to weekly P significantly improved PFS, the primary endpoint, compared with P alone, and toxicity with P+A was manageable with A dose reduction. These data support further evaluation of alisertib in ER+ HER2- MBC pts.
- Piqray (alpelisib) / Novartis
Double PIK3CA mutations in cis drive oncogene addiction and enhance sensitivity to PI3K alpha inhibitors in breast cancer (Hall 1 - Poster Session 3) - Sep 25, 2019 - Abstract #SABCS2019SABCS_1107;
inhibitors including alpelisib have recently been shown to be clinically active in ER+ PIK3CA mutant breast cancer...These findings implicate double PIK3CA mutations in cis as a novel mechanism of oncogene addiction relative to single hotspot mutations, providing a rationale to develop PI3K? inhibitors for the therapy of double PIK3CA mutant cancers.
- Piqray (alpelisib) / Novartis
Elucidating the synergistic relationship between the iNOS and PI3K/Akt pathways for treatment of metaplastic breast cancer (Hall 1) - Sep 25, 2019 - Abstract #SABCS2019SABCS_1035;
Our preliminary results suggest that LNMMA and Alpelisib combination treatment have therapeutic potential in the treatment of MBC. Our results indicated that simultaneous inhibition of the NOS and PI3K/AKT pathways may represent a clinically relevant therapeutic concept against hard-to-treat MBC, and warrants further studies.
- Herceptin (trastuzumab) / Roche, GDC-0084 / Kazia
Phase II trial of GDC-0084 in combination with trastuzumab for patients with HER2-positive breast cancer brain metastases (BCBM) (Hall 1 - Poster Session 1) - Sep 25, 2019 - Abstract #SABCS2019SABCS_977;
P2
The trial opened in February, 2019. NCT03765983.
- Ibrance (palbociclib) / Pfizer, letrozole / Generic mfg.
A Phase Ib dose escalation study evaluating the mutant selective PI3K-alpha inhibitor GDC-0077 (G) in combination with letrozole (L) with and without palbociclib (P) in patients with PIK3CA-mutant HR+/HER2- breast cancer (Hall 1) - Sep 25, 2019 - Abstract #SABCS2019SABCS_875;
P1
NCT03765983. This Phase Ib study of GDC-0077 in combination with letrozole with and without pabocicilb demonstrated a manageable safety profile combining GDC-0077 at its single agent recommended Phase II dose of 9 mg with letrozole with and without palbociclib at standard doses, with no evidence for DDI, high GDC-0077 dose intensity, and promising preliminary anti-tumor activity.
- An updated systematic review and meta-analysis of the safety and efficacy of phosphoinositide 3-kinase inhibitors (PI3Ki) in advanced breast cancer (Hall 1 - Poster Session 3) - Sep 25, 2019 - Abstract #SABCS2019SABCS_832;
Conclusion While selective PI3Ki have a better effect on ORR, DCR and PFS in patients with ABC compared to pan PI3Ki; their toxicity profile is still clinically substantial. Rigorous safety monitoring and early medical intervention are needed to reduce treatment discontinuation, optimize efficacy and render these drugs more clinically usable.
- Piqray (alpelisib) / Novartis, taselisib (GDC-0032) / Roche, IPI-549 / Infinity Pharma
Sub-group of PIK3CA WT breast cancer patients have hyperactive S1P signaling tumor cells responsive to PIK3-inhibitors: Functional signaling profile test identifies new patient group who may benefit from PIK3-targeted therapies (Hall 1 - Poster Session 1) - Sep 25, 2019 - Abstract #SABCS2019SABCS_791;
The abnormal levels of PI3K-involved signaling in PIK3CA WT patient breast cancer tumors were comparable in magnitude to levels found in well-characterized PI3KCA mutated breast tumor cell lines. Unlike the PIK3CA mutated cells lines, the bulk of the PIK3-involved signaling in the PIK3CA WT patient tumor cells was associated with the PI3K-gamma isoform rather than the PI3K-alpha isoform.
- GDC-0077 / Roche
GDC-0077 is a selective PI3K alpha inhibitor with robust efficacy in PIK3CA mutant hormone-positive breast cancer models (Hall 1 - Poster Session 3) - Sep 25, 2019 - Abstract #SABCS2019SABCS_748;
In vivo combination efficacy studies of GDC-0077 with fulvestrant and palbociclib also indicate the triple combination results in the greatest efficacy. Collectively, ourpreclinical data support evaluation of GDC-0077 in a triple combination with endocrine therapy and CDK4/6 inhibition in the clinic, in patients with locally advanced or metastatic hormone receptor positive breast cancer whose tumors harbor mutant PIK3CA.
- Talzenna (talazoparib) / Pfizer, gedatolisib (PF-05212384) / Curie Institute, Pfizer
Phase 2 trial with safety-run in of gedatolisib plus talazoparib in advanced triple negative or BRCA1/2 positive HER2 negative breast cancer (Hall 1) - Sep 25, 2019 - Abstract #SABCS2019SABCS_692;
Cohort B will remain at 12 since it is exploratory. Contact information: The study is being administered through the Big Ten Cancer Research Consortium and can be identified as BTCRC-BRE18-337.
- Keytruda (pembrolizumab) / Merck (MSD), Halaven (eribulin mesylate) / Eisai
A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes (KELLY study) (Hall 1 - Poster Session 3) - Sep 25, 2019 - Abstract #SABCS2019SABCS_667;
P2
E plus P was a safe and active regimen for pts with previously treated HR+/HER2- locally recurrent or MBC that merits further investigation. Exploratory biomarker analysis is pending.
- Kisqali (ribociclib) / Novartis, Verzenio (abemaciclib) / Eli Lilly
Different mechanism of CDK4/6 inhibitor resistance between ribociclib and abemaciclib (Stars at Night Ballroom 1&2 - 3rd Level) - Sep 25, 2019 - Abstract #SABCS2019SABCS_638;
However, the mechanism of resistance between ribociclib and abemaciclib might be different because the CDK6 level was different, although RB level was decreased in both RIBR and ABER. Furthermore, both p21 and p27 are considered as the internal inhibitors of CDK2, although more factors in RIBR and ABER were different.
- Development and characterization of PTEN IHC assay for testing breast cancer patients specimens (Hall 1 - Poster Session 1) - Sep 25, 2019 - Abstract #SABCS2019SABCS_629;
PTEN mutations and insertions/deletions contribute to PTEN protein loss. This study validates a simple method to interrogate PTEN status in clinical specimens and supports the utility of this test in selecting patients who are likely to respond to PI3K inhibitor treatment.
- Piqray (alpelisib) / Novartis
Clinical outcomes of alpelisib in hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer by next-generation sequencing-detected PIK3CA alteration status and phosphatase and tensin homolog loss: biomarker analysis from the SOLAR-1 study (Hall 1 - Poster Session 4) - Sep 25, 2019 - Abstract #SABCS2019SABCS_588;
These data demonstrate the efficacy of ALP in pts whose tumors harbor PIK3CA alterations as detected by NGS, including alterations that were not detectable by the PCR-based test used in SOLAR-1. Additional analyses suggest that ALP is also effective in pts with single and multiple PIK3CA mutations and in those whose tumors do not harbor a PIK3CA alteration but do have PTEN loss; however, low patient numbers in the PTEN loss subgroups may limit conclusions.
- paclitaxel / Generic mfg.
Identification of mechanisms driving acquired chemoresistance in preclinical breast cancer models of taxane resistance (Hall 1) - Sep 25, 2019 - Abstract #SABCS2019SABCS_555;
Western blotting confirmed alterations in the PI3K/Akt and MAPK pathways. PI3K inhibitors were found to have potent activity against the taxane resistant cell line models.
- ONC201 / Oncoceutics
ONC201 synergistically induces cell death in triple negative breast cancer with CDK 4/6 and MEK inhibition (Hall 1 - Poster Session 3) - Sep 25, 2019 - Abstract #SABCS2019SABCS_542;
MEK inhibitor trametinib and CDK4/6 inhibitor palbociclib demonstrated synergy with ONC201 yet palbociclib only in ONC201 sensitive CAL51. Detailed mechanisms of synergy are being investigated that can further guide clinical translation.
- Characterization of gene- and sample-level APOBEC mutagenesis enrichment with respect to intrinsic subtypes, tumor mutational burden, and immune composition in breast cancer (Hall 1 - Poster Session 1) - Sep 25, 2019 - Abstract #SABCS2019SABCS_535;
APOBEC mutagenesis patterns are seemingly prevalent across all breast cancer intrinsic subtypes and associate with elevated TMB and mutations in the PIK3CA helical loop domain and TP53 gene in TCGA breast cancer samples. Cancers with PIK3CA mutations in the helical loop domain did not demonstrate checkpoint gene overexpression, but were associated with other immunosuppressive features (e.g. TGFB3 and WNT5A overexpression).
- A PI3K-?d Inhibitor Combined with Irradiation Enhance the Antitumor Immune Effect of Anti-PD1 in Syngenic Triple Negative Breast Cancer Model. (Room W176) - Sep 24, 2019 - Abstract #ASTRO2019ASTRO_3532;
This study provides a preclinical rationale for the combination of PI3Kαδ inhibitor and RT with PD-1 blockade to overcome the immune tolerance of breast cancer. (Work supported by the grants from NRF #2017R1A2B4002710 & #2017M2A2A7A01018438.).
- letrozole / Generic mfg.
A neoadjuvant trial with letrozole identifies PRR11 in the 17q23 amplicon as a mechanism of resistance to endocrine therapy in ER-positive breast cancer (Hall 3) - Sep 23, 2019 - Abstract #SABCS2019SABCS_320;
P1
is required for the growth promoting effects of PRR11.These data suggest that 1) PRR11 is a mediator of resistance to antiestrogens via amplification of PI3K/AKT signaling, and 2) PI3K? is a potential therapeutic target in ER+ BCs harboring PRR11 amplification.
- Targeted - PI3K (Hall 1) - Sep 23, 2019 - Abstract #SABCS2019SABCS_265;
- | docetaxel / generics
Journal, PARP Biomarker: Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway. (Pubmed Central) - Sep 22, 2019
These data show that, for PCa cells, the cytotoxic effect of the DTX and TQ combination correlates with a block of the PI3K/AKT signaling pathway. These findings indicate that the combination of DTX and TQ, by blocking of the PI3K/AKT pathway, will improve the survival rate and quality of life of PCa patients.
- | Journal: MicroRNA-367 promotes progression of hepatocellular carcinoma through n PTENn /PI3K/AKT signaling pathway. (Pubmed Central) - Sep 22, 2019
PTEN might be a target of miR-367 in HCC. The inhibition of PTEN could reverse the anti-tumor action caused by the knockdown of miR-367 MiR-367 serves as an oncogene in HCC through activating the PI3K/AKT pathway by targeting PTEN.
- | Biomarker, Clinical, Journal: Expression of Phosphoinositide 3-Kinase p110α and p110β Subunits and PIK3CA Mutation in Patients With Advanced Gastric Carcinoma. (Pubmed Central) - Sep 22, 2019
Mutational status at this locus was not significantly correlated with clinicopathologic factors. These results imply that p110β could have a more important role in the progression and aggressiveness of AGC than p110α and has potential as a prognostic biomarker in patients with AGC.
- | doxorubicin hydrochloride / generics
Journal: Shikonin exerts antitumor activity in Burkitt's lymphoma by inhibiting C-MYC and PI3K/AKT/mTOR pathway and acts synergistically with doxorubicin. (Pubmed Central) - Sep 22, 2019
Importantly, we did not find the effect of shikonin on liver function in mice. In summary, these data suggest that shikonin may be an encouraging chemotherapeutic agent in the clinical treatment of BL.
- | Journal: Enhanced insulin receptor, but not PI3K, signalling protects podocytes from ER stress. (Pubmed Central) - Sep 22, 2019
However, contrary to this, knockdown of the negative regulator of PI3K-Akt signalling, phosphatase and tensin homolog deleted from chromosome 10 (PTEN), sensitizes podocytes to ER stress and apoptosis, despite increasing Akt phosphorylation. This indicates that protection from ER stress is conferred through not just the PI3K-Akt pathway, and indeed we find that inhibiting the MEK/ERK signalling pathway rescues PTEN knockdown podocytes from ER stress.
- | Herceptin (trastuzumab) / Roche
Biomarker, Journal, IO Biomarker: Genomic Profiling of HER2-Positive Gastric Cancer: PI3K/Akt/mTOR Pathway as Predictor of Outcomes in HER2-Positive Advanced Gastric Cancer Treated with Trastuzumab. (Pubmed Central) - Sep 22, 2019
PI3K/Akt/mTOR signaling pathway activation seems to have a differentially negative effect on overall survival and progression-free survival in AGC treated with trastuzumab-based chemotherapy. Combining different targeted agents could be a successful therapeutic strategy to improve the prognosis of HER2-positive AGC.
- | Biomarker, Journal: Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy. (Pubmed Central) - Sep 22, 2019
These results provide a framework for a biomarker-based substratification of patients with SDC in future targeted therapy. Cancer 2018;124:3523-32.
- | Zydelig (idelalisib) / Gilead, Copiktra (duvelisib) / Verastem
Journal: Discovery of a novel inhaled PI3Kδ inhibitor for the treatment of respiratory diseases. (Pubmed Central) - Sep 22, 2019
Once the potency was in the desired range, efforts were focused on identifying the particular physicochemical properties that could translate into better lung retention. This medicinal chemistry exercise led to the identification of LAS195319 as a candidate for clinical development.
- | Journal: Royleanone diterpenoid exhibits potent anticancer effects in LNCaP human prostate carcinoma cells by inducing mitochondrial mediated apoptosis, cell cycle arrest, suppression of cell migration and downregulation of mTOR/PI3K/AKT signalling pathway. (Pubmed Central) - Sep 22, 2019
This medicinal chemistry exercise led to the identification of LAS195319 as a candidate for clinical development. Taken together, we propose that royleanone could prove to be an important anticancer lead molecule for the treatment and overall management of prostate cancer, provided further in vivo studies are carried out.
- | Journal: Methyl eugenol induces potent anticancer effects in RB355 human retinoblastoma cells by inducing autophagy, cell cycle arrest and inhibition of PI3K/mTOR/Akt signalling pathway. (Pubmed Central) - Sep 22, 2019
Taken together, we propose that royleanone could prove to be an important anticancer lead molecule for the treatment and overall management of prostate cancer, provided further in vivo studies are carried out. The above results clearly indicate that ME is a potent anticancer agent and may be developed further as a possible anticancer lead molecule against retinoblastoma provided further in depth in vivo studies are carried out.
- | Journal: Tau-TCHF Inhibits Spleenic Apoptosis via PI3K-Akt Signaling Pathway in Chickens. (Pubmed Central) - Sep 22, 2019
And Tau-TCHF may be provided as feed additives in improving the immunity of animals. AKT (Ser473) and PDPK1 may be considered as further targets to study mechanism of Tau-TCHF on anti-apoptosis via PI3K-Akt signaling pathway.
- | Journal: Taurine Protects Against Arsenic-Induced Apoptosis Via PI3K/Akt Pathway in Primary Cortical Neurons. (Pubmed Central) - Sep 22, 2019
The decrease in p-Akt levels induced by arsenite exposure was prevented by taurine treatment. Thus, taurine attenuated the effect of arsenite on primary cortical neurons, an effect that may involve the Akt pathway.
- | Preclinical, Journal: Dracohodin Perochlorate Stimulates Fibroblast Proliferation via EGFR Activation and Downstream ERK/CREB and PI3K/Akt/mTOR Pathways In Vitro. (Pubmed Central) - Sep 21, 2019
Our findings suggest that DP-promoted fibroblast proliferation is stimulated by p-EGFR-induced activation of the ERK1/2-CREB and PI3K/Akt/mTOR pathways. Our present study explored the mechanism of DP-promoted fibroblast proliferation and provided a new basis for wound healing.
- |||| Clinical: Molecular testing in #thyroidcancer is needed: RET, NTRK, BRAF, PTEN, PI3K, ALK... New options and opportunities for patients. Let’s stop by the Oral Session at #ESMO19 @myESMO @Ja_Capdevila @aecat_es (Twitter) - Sep 21, 2019
- | Biomarker, Journal: Phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) follicular signalling is conserved in the mare ovary. (Pubmed Central) - Sep 20, 2019
PI3K, AKT1, JAK1 and STAT3 demonstrated redistributed localisation, from pregranulosa cells in fetal development, to both the oocyte and granulosa cells of follicles in the adult ovary, whilst negative feedback molecules PTEN and SOCS4 were only localised to the granulosa cells in the adult ovary. These findings suggest that the PI3K/AKT and JAK/STAT signalling pathways are utilised during folliculogenesis in the mare, similarly to previously studied mammalian species, and may serve as useful biomarkers for assessment of ovary development in the horse.
- | Preclinical, Journal: S-oxiracetam ameliorates ischemic stroke induced neuronal apoptosis through up-regulating α7 nAChR and PI3K / Akt / GSK3β signal pathway in rats. (Pubmed Central) - Sep 20, 2019
Furthermore, S-ORC inhibited neuronal apoptosis by activating the PI3K/Akt/GSK3β signaling pathway via α7 nAChR, which was evidenced by α7 nAChR siRNA. In conclusion, our findings strongly suggest that S-ORC could be used as an effective neuroprotective agent for ischemic stroke due to its effect in preventing neuronal apoptosis.
- | Venclexta (venetoclax) / Roche, AbbVie, ibrutinib / Generic mfg.
Journal, Combination therapy: Venetoclax as a single agent and in combination with PI3K-MTOR1/2 kinase inhibitors against ibrutinib sensitive and resistant mantle cell lymphoma. (Pubmed Central) - Sep 20, 2019
In conclusion, our findings strongly suggest that S-ORC could be used as an effective neuroprotective agent for ischemic stroke due to its effect in preventing neuronal apoptosis. No abstract available
- | Journal: Caveolin-1 deficiency protects pancreatic β cells against palmitate-induced dysfunction and apoptosis. (Pubmed Central) - Sep 20, 2019
Furthermore, under PA induced endoplasmic reticulum (ER) stress, Cav-1 silencing significantly reduced eIF2α phosphorylation and the expression of ER stress-responsive markers BiP and CHOP, which are among the known sensitizers of lipotoxicity. Our findings suggest Cav-1 as potential target molecule in T2DM treatment via the preservation of lipotoxicity-induced β-cell mass reduction and the attenuation of insulin secretion dysfunction.
- CD73 PROMOTES HEPATOCELLULAR CARCINOMA PROGRESSION AND METASTASIS VIA ACTIVATING PI3K/AKT SIGNALING BY INDUCING RAP1-MEDIATED MEMBRANE LOCALIZATION OF P110ß AND PREDICTS POOR PROGNOSIS () - Sep 20, 2019 - Abstract #ILCA2019ILCA_184;
CD73 promotes progression and metastasis through activating PI3K/AKT signaling, indicating a novel prognostic biomarker for HCC. Our data demonstrate the importance of CD73 in HCC in addition to its immuosuppressive functions and revealed that co-targeting CD73 and A2AR strategy may be a promising novel therapeutic strategy for future HCC management.
- | PIK-75 / Pathway Therapeutics, CI-1040 / Pfizer
Journal: Phosphoinositide 3-kinase p110α negatively regulates thrombopoietin-mediated platelet activation and thrombus formation. (Pubmed Central) - Sep 20, 2019
Acetylsalicylic acid (ASA) blocked the enhancement of thrombus formation by TPO in both WT and p110α KO mice. Together, these results demonstrate that p110α negatively regulates TPO-mediated enhancement of platelet function by restricting ERK phosphorylation and TxA synthesis in a manner independent of its kinase activity.
- | quercetin (LY294002) / Eli Lilly
Journal: Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway. (Pubmed Central) - Sep 20, 2019
Our results suggest that ADSCs likely facilitate wound healing via the release of exosomes, and the PI3K/Akt pathway may play a role in this process. Our data also suggest that the clinical application of ADSC-derived exosomes may shed new light on the use of cell-free therapy to accelerate full-thickness skin wound healing and attenuate scar formation.
- | Journal: Primary immunodeficiency disorder caused by phosphoinositide 3-kinase delta (PI3Kδ) deficiency. (Pubmed Central) - Sep 20, 2019
First publication on human PI3Kδ deficiency. Two patients carrying novel homozygous loss-of-function mutation in PIK3CD, resulting in PI3Kδ deficiency, developed a primary immunodeficiency disorder characterized by hypogammaglobulinemia and inflammatory bowel disease.
- | Journal: Molecular Basis for Membrane Recruitment by the PX and C2 Domains of Class II Phosphoinositide 3-Kinase-C2α. (Pubmed Central) - Sep 20, 2019
The C2 domain preferentially binds to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate, and low-resolution structures of the combined PX-C2 module by small-angle X-ray scattering reveal a compact conformation in which cooperative lipid binding by each domain binding can occur. Finally, we demonstrate an unexpected role for calcium in perturbing the membrane interactions of the PX-C2 module, which we speculate may be important for regulating the activity of PI3K-C2α.
- | Journal: PI3K-AKT-FOXO1 pathway targeted by skeletal muscle microRNA to suppress proteolytic gene expression in response to carbohydrate intake during aerobic exercise. (Pubmed Central) - Sep 20, 2019
The expression of PTEN was lower (P < 0.05) in REC CHO than CON, while MURF1 was lower (P < 0.05) POST CHO than CON. These findings suggest the mechanism by which microRNA facilitate skeletal muscle adaptations in response to exercise with carbohydrate and protein feeding is by inhibiting markers of proteolysis.