 |
67 Companies | 59 Products |
|
|
59 Products | |
344 Diseases | |
342 Trials |  |
12240 News |  |
| «12...7576777879808182838485...229230» |
- | Journal: Lipoxin A4 protects against paraquat‑induced acute lung injury by inhibiting the TLR4/MyD88‑mediated activation of the NF‑κB and PI3K/AKT pathways. (Pubmed Central) - Nov 12, 2021
Furthermore, the in vitro experiments further confirmed that the beneficial effects of LXA4 on PQ‑induced damage were TLR4‑dependent. Hence, the present study demonstrated that LXA4 attenuated PQ‑induced toxicity in lung tissue and RAW264.7 macrophages, and that this protective effect may be closely related to the mitigation of inflammatory responses, oxidative stress damage and the TLR4/MyD88‑mediated activation of the PI3K/AKT/NF‑κB pathway.
- || Clinical, Clinical data, Journal, Tumor Mutational Burden, PD(L)-1 Biomarker, IO biomarker: A genomic instability-derived risk index predicts clinical outcome and immunotherapy response for clear cell renal cell carcinoma. (Pubmed Central) - Nov 12, 2021
Besides, we predicted several drugs (PI3K inhibitor, ATPase inhibitor, and phenylalanyl tRNA synthetase inhibitor) targeting risk subgroups. The well established GIRI was an effective cancer biomarker for predicting ccRCC prognosis and provided apotential reference value for identifying immunotherapy response.
- | Procoralan (ivabradine) / Amgen, Servier, Ono Pharma
Preclinical, Journal: Ivabradine protects rats against myocardial infarction through reinforcing autophagy via inhibiting PI3K/AKT/mTOR/p70S6K pathway. (Pubmed Central) - Nov 12, 2021
In summary, these findings demonstrated that Iva attenuated MI in rats by enhancing autophagy, and PI3K/AKT/mTOR/p70S6K pathway might be involved in the process. Autophagy activation by Iva may be a potential therapeutic strategy for the treatment of MI.
- | Journal: Seasonal expressions of ERα, ERβ, EGF, EGFR, PI3K and Akt in the scent glands of the muskrats (Ondatra zibethicus). (Pubmed Central) - Nov 12, 2021
Besides, the concentrations of 17β-estradiol (E) in the serum and the scent glandular tissues were remarkably higher in the breeding season than those of the non-breeding season. Taken together, our results suggested that EGFR signaling pathway may coordinate with ERs signaling to regulate the seasonal changes of the scent glandular functions.
- | Journal: Design, Synthesis and SAR in 2,4,7-Trisubstituted Pyrido[3,2-d]Pyrimidine Series as Novel PI3K/mTOR Inhibitors. (Pubmed Central) - Nov 12, 2021
Six novel derivatives possess IC values on PI3Kα between 3 and 10 nM. The compounds with the best efficiencies on PI3K and mTOR induced micromolar cytotoxicity on cancer cell lines possessing an overactivated PI3K pathway.
- | Journal: Mechanism of PI3K/AKT/mTOR signaling pathway for mediating anti-inflammatory and anti-oxidant effects of chrysin: a protein microarray-based study (Pubmed Central) - Nov 12, 2021
The compounds with the best efficiencies on PI3K and mTOR induced micromolar cytotoxicity on cancer cell lines possessing an overactivated PI3K pathway. Chrysin can inhibit the synthesis of the upstream signaling molecule ROS to inhibit the activation of AKT/mTOR signaling pathway, regulate the translation process of ribosomes, down-regulate the synthesis and release of pro-inflammatory cytokines and inflammatory mediators, and thus produce anti-inflammatory effects.
- | Preclinical, Journal: MiR-126 affects femoral fracture healing in rats through PI3K/AKT signaling pathway. (Pubmed Central) - Nov 11, 2021
Chrysin can inhibit the synthesis of the upstream signaling molecule ROS to inhibit the activation of AKT/mTOR signaling pathway, regulate the translation process of ribosomes, down-regulate the synthesis and release of pro-inflammatory cytokines and inflammatory mediators, and thus produce anti-inflammatory effects. No abstract available
- | quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Ephedrine alleviates middle cerebral artery occlusion-induced neurological deficits and hippocampal neuronal damage in rats by activating PI3K/AKT signaling pathway. (Pubmed Central) - Nov 11, 2021
Furthermore, administration of PI3K/AKT pathway inhibitor LY294002 abolished the beneficial effects of EPH. These results confirmed that EPH alleviated brain injury induced by MCAO via activating PI3K/AKT signaling pathway.
- | Journal: The COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway. (Pubmed Central) - Nov 11, 2021
Through the TGF-β/PI3K/AKT pathway, COL-4A1 interferes with the pathogenesis of PE. Thus COL-4A1 is expected to become a potential target of PE, providing a basis for exploring the treatment of PE.
- || Clinical, Journal: Effect of Electro-acupuncture on Expression of IRS-1/PI3K/GLUT4 Pathway in Ovarian Granulosa Cells of Infertile Patients with Polycystic Ovary Syndrome-Insulin Resistance of Phlegm-Dampness Syndrome. (Pubmed Central) - Nov 10, 2021
(Registration No. ChiCTR1800015453).
- | Preclinical, Journal: Panax Notoginseng Saponins suppresses TRPM7 via the PI3K/AKT pathway to inhibit hypertrophic scar formation in vitro. (Pubmed Central) - Nov 10, 2021
This study suggested that PNS hampered scar formation might via inhibiting ECM and stimulating cell apoptosis by modulating the PI3K/AKT signaling. Overall, these findings in the present study could support the use of PNS for preventing HS formation, and TRPM7 may be a novel molecular target for treating HS.
- | Farydak (panobinostat) / Novartis
Journal, Epigenetic controller: Abrogation of histone deacetylases (HDACs) decreases survival of chronic myeloid leukemia cells: new insight into attenuating effects of the PI3K/c-Myc axis on panobinostat cytotoxicity. (Pubmed Central) - Nov 10, 2021
Meanwhile, we found that upon blockage of autophagy and the proteasome pathway, as the main axis involved in the activation of autophagy, the anti-leukemic property of the HDAC inhibitor was potentiated. Taken together, our study suggests the beneficial application of HDAC inhibition in the treatment strategies of CML; however, further in vivo studies are needed to determine the efficacy of this inhibitor, either as a single agent or in combination with small molecule inhibitors of PI3K and/or c-Myc in this malignancy.
- | Journal: PTEN mediates serum deprivation-induced cytotoxicity in H9c2 cells via the PI3K/AKT signaling pathway. (Pubmed Central) - Nov 10, 2021
All these effects could be reversed by phosphatidylinositol 3-kinase (PI3K) inhibitor, which indicated the PI3K/protein kinase B (AKT) might be the critical component of the PTEN effects during serum deficiency. In conclusion, our study indicated the role of the PTEN/PI3K/AKT pathway in serum deprivation-induced cytotoxicity in H9c2 cells.
- | Preclinical, Journal: Wide Pulse Width Electroacupuncture Ameliorates Denervation-Induced Skeletal Muscle Atrophy in Rats via IGF-1/PI3K/Akt Pathway. (Pubmed Central) - Nov 10, 2021
EA with 200-ms pulse width was found to have a more significant effect than 0.5-ms EA. The positive effects of EA disappeared after inhibition of the PI3K/Akt pathway.
- | Preclinical, Journal: New insights into the effects of vinpocetine against neurobehavioral comorbidities in a rat model of temporal lobe epilepsy via the downregulation of the hippocampal PI3K/mTOR signalling pathway. (Pubmed Central) - Nov 10, 2021
The positive effects of EA disappeared after inhibition of the PI3K/Akt pathway. VNP is a valuable candidate for epilepsy therapy via its modulation of the mechanisms underlying epileptogenesis with emphasis on its modulatory effect on mTOR signalling pathway.
- | fluvastatin / Generic mfg.
Journal: Fluvastatin protects neuronal cells from hydrogen peroxide-induced toxicity with decreasing oxidative damage and increasing PI3K/Akt/mTOR signalling. (Pubmed Central) - Nov 10, 2021
Our work demonstrates the beneficial effects of fluvastatin in neuronal cells under pathological conditions, and, furthermore, this is via prenylation-independent activation of PI3K/Akt/mTOR pathway. Our data highlights the functional significance of the PI3K/Akt/mTOR pathway in neuronal cells in response to oxidative stress.
- | Journal: "Olfactory three-needle" acupuncture enhances synaptic function in Aβ-induced Alzheimer's disease via activating PI3K/AKT/GSK-3β signaling pathway. (Pubmed Central) - Nov 10, 2021
Additionally, the activation level of PI3K/AKT signaling and the phosphorylation inactivation of GSK-3β were significantly enhanced by the "olfactory three-needle". Our findings suggested that the three-needle acupuncture is a potential alternative to improve synaptic plasticity and neuronal survival of Alzheimer's disease brain in rodents.
- | quercetin (LY294002) / Eli Lilly
Journal: Calcyclin (S100A6) Attenuates Inflammatory Response and Mediates Apoptosis of Chondrocytes in Osteoarthritis via the PI3K/AKT Pathway. (Pubmed Central) - Nov 10, 2021
Our findings suggested that the three-needle acupuncture is a potential alternative to improve synaptic plasticity and neuronal survival of Alzheimer's disease brain in rodents. We investigated that Calcyclin (S100A6) relieved the inflammation and mediated the chondrocyte apoptosis through PI3K/AKT pathway and we confirmed that S100A6 might be an attractive therapeutic target.
- | PF-04691502 / Pfizer
Journal: PI3K/mTOR Dual Inhibitor PF-04691502 Is a Schedule-Dependent Radiosensitizer for Gastroenteropancreatic Neuroendocrine Tumors. (Pubmed Central) - Nov 10, 2021
Our results demonstrate that schedule-dependent administration of a PI3K/mTOR inhibitor, combined with XRT, can enhance cytotoxicity by promoting the radiosensitivity of NET cells. Moreover, our findings suggest that radiotherapy, in combination with timed PI3K/mTOR inhibition, may be a promising therapeutic regimen for patients with GEP-NET.
- || Review, Journal: Xmrks the Spot: Fish Models for Investigating Epidermal Growth Factor Receptor Signaling in Cancer Research. (Pubmed Central) - Nov 10, 2021
At the same time, both activate the Ras/Raf/MEK/MAPK pathway to regulate cell proliferation and E-cadherin signaling. Xmrk models of melanoma have shown that inhibitors of PI3K and MEK have an anti-cancer effect, and in HCC, that the steroidal drug, adrenosterone, can prevent metastasis and recover E-cadherin expression, suggesting that fish Xmrk models can exploit similarities with EGFR signal transduction to identify and study new chemotherapeutic drugs.
- | Journal: ID2 Inhibits Bladder Cancer Progression and Metastasis via PI3K/AKT Signaling Pathway. (Pubmed Central) - Nov 10, 2021
Mechanistically, ID2 acts as a tumor suppressor through PI3K/AKT signaling pathway to inhibit the progression and metastasis of BCa. Our results suggest that ID2 exerts tumor suppressive effects in BCa through PI3K/AKT signaling pathway, and altered ID2 expression can be used as a biomarker of BCa progression and metastasis.
- | Journal: Ras/ERK and PI3K/AKT signaling differentially regulate oncogenic ERG mediated transcription in prostate cells. (Pubmed Central) - Nov 10, 2021
In contrast, AKT activation altered the ERG cistrome and promoted expression of luminal cell fate genes. These data suggest that, depending on AKT status, ERG can promote either luminal or EMT transcription programs, but ERG can promote tumorigenesis independent of these cell fates and tumorigenesis requires only the transcriptional activation function.
- | Journal: Fluoride regulates chondrocyte proliferation and autophagy via PI3K/AKT/mTOR signaling pathway. (Pubmed Central) - Nov 10, 2021
MHY1485 also recovered the downregulation of proliferative chondrocytes markers Sox9 and Type Ⅱ Collagen (Col2a1) induced by fluoride in ATDC5 cells. Taken together, our result demonstrated that fluoride suppressed proliferation and facilitated autophagy via PI3K/AKT/mTOR signaling pathway in chondrogenesis.
- | gemcitabine / Generic mfg.
Journal: STK39 enhances the progression of Cholangiocarcinoma via PI3K/AKT pathway. (Pubmed Central) - Nov 10, 2021
Moreover, the increased expression of STK39 may be mediated by the dysregulation of miR-26a-5p. In summary, STK39 could be served as a valuable prognostic candidate and a potential therapeutic target of CCA.
- ||||| Checkpoint inhibition: ⚡️ Synergistic antitumor activity of pan-PI3K inhibition and immune checkpoint blockade in #bladdercancer @jitcancer https://t.co/RJPNDutTWm (Twitter) - Nov 9, 2021
- | quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Connectivity map analysis identifies fisetin as a treatment compound for osteoporosis through activating the PI3K-AKT signaling pathway in mouse pre-osteoblastic MC3T3-E1 cells. (Pubmed Central) - Nov 7, 2021
In summary, STK39 could be served as a valuable prognostic candidate and a potential therapeutic target of CCA. Our results demonstrated that fisetin could promote MC3T3-E1 cell proliferation, differentiation and increase OPG/RANKL expression ratio through activating the PI3K-AKT pathway, which has potential for the treatment of osteoporosis.
- | Journal: GDP induces PANC-1 human pancreatic cancer cell death preferentially under nutrient starvation by inhibiting PI3K/Akt/mTOR/autophagy signaling pathway. (Pubmed Central) - Nov 7, 2021
Mechanistically, GDP inhibited PI3K/Akt/mTOR/autophagy survival signaling pathway, leading to selective PANC-1 cancer cell death under the nutrition starvation condition. Therefore, GDP is a promising anti-austerity agent for drug development against pancreatic cancer.
- | Journal: PTEN loss promotes oncogenic function of STMN1 via PI3K/AKT pathway in lung cancer. (Pubmed Central) - Nov 7, 2021
The high expression of STMN1 was negatively correlated with the low expression of PTEN in lung cancer specimens. Overall, our work demonstrated that PTEN regulated the oncogenic function of STMN1 in lung cancer.
- | Preclinical, Journal, IO biomarker: Piclamilast mitigates 1,2-dimethylhydrazine induced colon cancer in rats through modulation of Ras/PI3K/Akt/mTOR and NF-κβ signaling. (Pubmed Central) - Nov 7, 2021
The results of this study show that PIC may be a promising therapeutic agent for the treatment of CRC. PIC might inhibit the proliferation of CRC cells and induce apoptosis via multiple mechanisms that involve its antioxidant effect and inhibition of NF-κβ and Ras/PI3K/Akt/mTOR signaling.
- |||| Heterogeneity: Innovative therapy for #penilecancer-challenging rare tumor with molecular heterogeneity (HER, PI3K, Notch, DNA-repair, cell-cycle alterations), generally low TMB-VEGF+PD1i promising-HPV targeting T-cells being evaluated @JadChahoud @MoffittNews @GTumors https://t.co/IDMrUmIK0R (Twitter) - Nov 6, 2021
- | Preclinical, Journal: Morroniside suppresses hydrogen peroxide-stimulated autophagy and apoptosis in rat ovarian granulosa cells through the PI3K/AKT/mTOR pathway. (Pubmed Central) - Nov 6, 2021
Finally, we showed that treatment with PI3K and mTOR inhibitors reversed the protective effects of morroniside on HO-induced granulosa cells. Taken together, our data suggest that treatment with morroniside decreased apoptosis, autophagy, and oxidative stress in rat granulosa cells through the PI3K/AKT/mTOR pathway.
- | Journal: The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway. (Pubmed Central) - Nov 6, 2021
Taken together, our data suggest that treatment with morroniside decreased apoptosis, autophagy, and oxidative stress in rat granulosa cells through the PI3K/AKT/mTOR pathway. Our findings indicate that METTL14 partakes in the biological process of GC as a tumor suppressor and may be an emerging biomarker in GC.
- | Journal: Combining combretastatin A4 phosphate with ginsenoside Rd synergistically inhibited hepatocellular carcinoma by reducing HIF-1α via PI3K/AKT/mTOR signalling pathway. (Pubmed Central) - Nov 6, 2021
The mechanism may be related to the inhibition of HIF-1α by PI3K/AKT/mTOR signalling pathway. This strategy provides a new thought for the combinative therapy of VDAs.
- | Journal: LncRNA Bmp1 promotes the healing of intestinal mucosal lesions via the miR-128-3p/PHF6/PI3K/AKT pathway. (Pubmed Central) - Nov 6, 2021
Furthermore, PHF6 overexpression affected IEC-6 cells by activating PI3K/AKT signaling which was mediated by the miR-128-3p/PHF6 axis. In conclusion, Bmp1 was found to promote the expression of PHF6 through the sponge miR-128-3p, activating the PI3K/AKT signaling pathway to promote cell migration and proliferation.
- | Journal: LncRNA PSMA3-AS1 promotes cell proliferation, migration, and invasion in ovarian cancer by activating the PI3K/Akt pathway via the miR-378a-3p/GALNT3 axis. (Pubmed Central) - Nov 6, 2021
Moreover, PSMA3-AS1 activated the PI3K/Akt pathway by upregulating GALNT3 expression. Overall, PSMA3-AS1 promotes OC cell proliferation, migration, invasion, and xenograft tumor growth by activating the PI3K/Akt pathway via the miR-378a-3p/GALNT3 axis.
- | Journal, IO biomarker: microRNA-10b promotes the apoptosis of bovine ovarian granulosa cells by targeting plasminogen activator inhibitor-1. (Pubmed Central) - Nov 6, 2021
Finally, a PI3K/AKT inhibitor (Miltefosine) was used to inhibit the PI3K/AKT pathway, which reversed the inhibitory effect of PAI-1 on the apoptosis of BGCs (P < 0.05), and enhanced the promotion effect of miR-10b on the apoptosis of BGCs (P < 0.05). Our results indicated that miR-10b promotes BGC apoptosis by targeting PAI-1 to regulate the PI3K/AKT pathway.
- | Journal: ACY1 regulating PTEN/PI3K/AKT signaling in the promotion of non-small cell lung cancer progression. (Pubmed Central) - Nov 5, 2021
This study reveals that ACY1 may promote the progression of NSCLC via activating PI3K/AKT signaling in a PTEN-dependent manner. Our study may provide a better understanding of the pathogenesis and development of NSCLC.
- | Journal: miR-151-5p alleviates corneal allograft rejection by activating PI3K/AKT signaling pathway and balancing Th17/Treg after corneal transplantation via targeting IL-2Rɑ. (Pubmed Central) - Nov 5, 2021
Similarly, upregulation of miR-151-5p alleviated CGR via activation of the PI3K/AKT signaling pathway and balancing of Th17/Treg, and upregulation of IL-2Rɑ abolished the alleviating effect of miR-151-5p. Upregulation of miR-151-5p alleviated CGR by activating the PI3K/AKT signaling pathway and balancing Th17/Treg via targeting of IL-2Rɑ, which contributes to improving the results of CT.
- | erlotinib / Generic mfg.
Journal, Epigenetic controller: Phospho-EGFRTyr992 is synergistically repressed by co-inhibition of histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K), which attenuates resistance to erlotinib in head and neck cancer cells. (Pubmed Central) - Nov 5, 2021
These findings indicate that HDACs and PI3K co-inhibition sensitizes erlotinib via inactivation of the phosphor-EGFRTyr1068-induced RTK-STAT3 axis. However, PI3K inhibition was sufficient to sensitize TU212 cells to erlotinib, providing new perspectives for the further clinical study of erlotinib + vorinostat + copanlisib as a potential combination therapeutic solution for EGFR responsive reactivation-induced resistance to erlotinib.
- | mirdametinib (PD-0325901) / SpringWorks Therap, BeiGene, Koselugo (selumetinib) / Merck (MSD), AstraZeneca, GDC 0879 / Roche
Journal, Cancer stem cells: MEK1/2 is a bottleneck that induces cancer stem cells to activate the PI3K/AKT pathway. (Pubmed Central) - Nov 5, 2021
Moreover, converted cells gained migration and invasion abilities assessed by in vitro assays. Therefore, the inhibition of MEK1/2 was found to be critical for the conversion of normal stem cells into CSCs in the tumor-inducing microenvironment.
- Mekinist (trametinib) / Novartis, taselisib (GDC-0032) / Roche, Cotellic (cobimetinib) / Exelixis, Roche
Dual Inhibition of the MEK/ERK and PI3K/AKT Pathways Prevents Pulmonary Graft-Versus-Host Disease through Suppression of Arteriovenous Inflammation and Bronchiolitis (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5504;
Vehicles, the MEK inhibitors trametinib (tra) 0.1 mg/kg/day, cobimetinib (cobi) 0.1 mg/kg/day, the PI3K inhibitor taselisib (tase) 5 mg/kg/day and tacrolimus (tac) 1 mg/kg were given from day 0 through 28...Furthermore, phosphorylation of ERK1/2 and AKT is upregulated in human pGVHD. Given that dual inhibition of MEK/ERK and PI3K/AKT signaling suppresses vascular inflammation and bronchiolitis thorough inhibition of B cells and monocytes in mice, this strategy may provide a novel treatment option against human pGVHD.
- Venclexta (venetoclax) / Roche, AbbVie
An Observational Study on Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with Venetoclax-Based Regimens Outside Clinical Trials in Italy (GIMEMA CLL1920) (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5441;
When we compared the outcome of patients treated with venetoclax monotherapy vs VenR, the addition of anti-CD20 MoAb allowed to reach deeper responses by significantly increasing the CR rate. As the study and its data collection are still ongoing, the updated analysis of an expanded cohort with longer follow-up will be presented at the meeting.
- MK-1026 / Merck (MSD)
Efficacy and Safety of the BTK Inhibitor MK-1026 in Patients with Hematologic Malignancies: Phase 2 Study (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5432;
P2
Duration of response will be estimated by the Kaplan-Meier method. Safety will be assessed in all treated patients.
- Ukoniq (umbralisib) / TG Therap, Utuxin (ublituximab) / TG Therap
Efficacy and Safety of Ublituximab in Combination with Umbralisib (U2) in Patients with Chronic Lymphocytic Leukemia (CLL) By Treatment Status: A Sub-Analysis of the Phase 3 Unity-CLL Study (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5421;
P3
Of the 210 patients treated with U2, 119 were TN and 91 were PT. TN patients had a median age of 68 years (39 – 88 years) and 63% were male.
- Zydelig (idelalisib) / Gilead, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche, Calquence (acalabrutinib) / AstraZeneca
A Quality-Adjusted Survival (Q-TWiST) Analysis to Assess Benefit-Risk of Acalabrutinib Versus Idelalisib/Bendamustine Plus Rituximab or Ibrutinib Among Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) Patients (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5417;
This analysis demonstrated that Acala treatment is significantly superior to IR/BR treatment. Quality-adjusted survival gains of Acala over Ibr varied by toxicity definition, but was numerically higher for Acala.
- BR101801 / Boryung Group
A Phase 1 Dose Escalation Study of Dual PI3K and DNA PK Inhibitor, BR101801 in Adult Patients with Advanced Hematologic Malignancies (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5250;
P1
BR101801 was well tolerated and showed preliminary signs of activity in patients with relapsed or refractory hematologic malignancies. The phase Ib/II study of BR101801 is warranted in relapsed/refractory NHL.
- Opdivo (nivolumab) / Ono Pharma, BMS, Aliqopa (copanlisib) / Bayer
A Phase I Trial of PI3Kαδ Inhibitor Copanlisib in Combination with Nivolumab in Patients with Richter’s Transformation (RT) or Transformed Non-Hodgkin Lymphoma (tNHL) (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5246;
P1
We identified COPA 45 mg IV on days 1, 8 and 15 as the MTD/RP2D in combination with nivolumab in patients with R/R RT and tFL. This combination was well-tolerated at the MTD/RP2D, and the study is currently enrolling patients in an expansion cohort to further characterize the efficacy of this regimen.
- Transcriptional Reprogramming of Super-Enhancer Associated Oncogenes Following Inhibition of Cyclin-Dependent Kinase-9 (CDK9) in Aggressive Non-Hodgkin Lymphoma (NHL) (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5178;
ChIP-Seq analysis confirmed increased global RNAPII pausing at promoters in cells treated with AZD4573, including at recovery genes...Combination of BET bromodomain inhibitor JQ1 and CDK9i reduced expression of recovery genes including MYC and synergistically restricted proliferation of NHL cells...To investigate recovery genes as targets, we used PIM kinase inhibitors SGI1776 (PIM1) and AZD1208 (pan-PIM)...CDK9i leads to transcriptional reprogramming including the upregulation of a subset of SE-associated oncogenes. Targeting recovery oncogenes may enhance sensitivity to CDK9i.
- Venclexta (venetoclax) / Roche, AbbVie
Targeting EZH2 Promotes Chemosensitivity of BCL-2 Inhibitor through PIK3IP1-PI3K/AKT Axis in Acute Myeloid Leukemia (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5023;
Venetoclax (Ven, ABT-199), a BCL-2 selective inhibitor has anti-tumor activity in AML but its overall response rate of monotherapy was unsatisfied owing to the clinical resistance to the inhibitor...Our results also reveal a novel mechanism that accounts for the synergistic effect of the two drugs and the fact that DZNeP may increase the chemosensitivity of BCL-2 inhibitor through PIK3IP1-PI3K/AKT axis in AML. Our findings suggest the potential combined therapy of Ven+DZNeP for AML.
- LY294002 / Eli Lilly
Anti-Apoptotic Effect of Angelica Polysaccharide (APS) on Cryopreservation of Platelets (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4922;
The effects of APS on cells treated with Ly294002, PI3K inhibitor and the effect of APS on the p-AKT were also studied... APS, like TPO, has an anti-apoptotic effect on the cryopreserved platelets and megakaryocytes through activating PI3K/AKT, decreasing the expression of Caspase-3 and inhibiting the reduction of MMP.