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- | mitoxantrone / Generic mfg.
Journal: Flavonoid Monomers as Potent, Nontoxic, and Selective Modulators of the Breast Cancer Resistance Protein (ABCG2). (Pubmed Central) - Feb 16, 2022
Moreover, it significantly reduces the abundance of functional BCRP dimers/oligomers by half to retain more mitoxantrone in the BCRP-overexpressing cell line and that may account for its inhibitory activity. They are promising candidates to be developed into combination therapy to overcome MDR cancers with BCRP overexpression.
- | Journal: Protein Tyrosine Phosphatase 1B(PTP1B) promotes melanoma cells progression through Src activation. (Pubmed Central) - Feb 16, 2022
Moreover, we found that PTP1B could interact with Src via coimmunoprecipitation and dephosphorylation of the Tyr530 site. Collectively, our study revealed that PTP1B can promote melanoma cell metastasis by interacting with Src and provides a theoretical basis for future applications of PTP1B inhibitors in the treatment of malignant melanoma.
- | Journal: Inhibitor Combinations Reveal Wiring of the Proteostasis Network in Prostate Cancer Cells. (Pubmed Central) - Feb 16, 2022
Based on RNA-seq, these relationships are associated, in part, with activation of stress pathways. Together, these results suggest that cocktails of proteostasis inhibitors might be a powerful way of treating some cancers, although antagonism that blunts the efficacy of both molecules is also possible.
- | captopril / Generic mfg.
Journal: The angiotensin-converting enzyme inhibitor, captopril, suppressed Hepatic Stellate Cell activation via NF-kappaB or wnt3α/β-catenin pathway. (Pubmed Central) - Feb 16, 2022
In conclusion, in HG-stimulated HSC-T6 cells, captopril displayed a potent ability to inhibit oxidative stress, inflammation and hepatic fibrogenesis via NF-kappaB or wnt3α/β-catenin. These results demonstrated the mechanism of captopril as well as the role of the NF-kappaB or wnt3α/β-catenin on HSC-T6 activation induced by HG.
- || Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Clinical, Journal: Risk of lower extremity amputations in patients with type 2 diabetes using sodium-glucose co-transporter 2 inhibitors. (Pubmed Central) - Feb 16, 2022
Compared with DPP-4i use, SGLT2i use did not result in a statistically significant higher overall risk of lower extremity amputations. However, the results suggest that SGLT2i may increase the risk of amputation with long-term use.
- | macozinone (PBTZ169) / Innovative Medicines for Tuberculosis, Nearmedic, Bill & Melinda Gates Foundation
Journal: Structural and Activity Relationships of 6-Sulfonyl-8-Nitrobenzothiazinones as Antitubercular Agents. (Pubmed Central) - Feb 16, 2022
Compared to PBTZ169, both compounds displayed increased aqueous solubility and higher stability in human liver microsomes. This study suggested that an alternative side-chain modification strategy could be implemented to improve the druglike properties of the BTZ-based compounds.
- | Biomarker, Journal, Tumor microenvironment: Developing a Novel Indium(III) Agent Based on Liposomes to Overcome Cisplatin-Induced Resistance in Breast Cancer by Multitargeting the Tumor Microenvironment Components. (Pubmed Central) - Feb 16, 2022
We also confirmed the mechanism by which 5b/5b-Lip overcomes breast cancer cell resistance. 5b/5b-Lip cannot act against DNA in cancer cells but attacks the two cell components in the tumor microenvironment, namely, by inducing apoptosis and lethal autophagy of cancer cells and resetting tumor-promoting M2 macrophages to the tumor-killing M1 phenotype.
- | APG-5918 / Ascentage Pharma
Journal: Discovery of EEDi-5273 as an Exceptionally Potent and Orally Efficacious EED Inhibitor Capable of Achieving Complete and Persistent Tumor Regression. (Pubmed Central) - Feb 16, 2022
Co-crystal structures of two potent EED inhibitors with EED provide a solid structural basis for their high-affinity binding. EEDi-5273 is a promising EED inhibitor for further advanced preclinical development for the treatment of human cancer and other human diseases.
- || BMS 963272 / BMS
Clinical, Journal: Screening Hit to Clinical Candidate: Discovery of BMS-963272, a Potent, Selective MGAT2 Inhibitor for the Treatment of Metabolic Disorders. (Pubmed Central) - Feb 16, 2022
A novel chemistry route was developed to synthesize aryl dihydropyridinone analogs to explore structure-activity relationship around this hit, leading to the discovery of potent and selective MGAT2 inhibitors 21f, 21s, and 28e that are stable to liver microsomal metabolism. After triaging out 21f due to its inferior in vivo potency, pharmacokinetics, and structure-based liabilities and tetrazole 28e due to its inferior channel liability profile, 21s (BMS-963272) was selected as the clinical candidate following demonstration of on-target weight loss efficacy in the diet-induced obese mouse model and an acceptable safety and tolerability profile in multiple preclinical species.
- | Journal: Exploring the mechanism of Jianpi Qushi Huayu Formula in the treatment of chronic glomerulonephritis based on network pharmacology. (Pubmed Central) - Feb 16, 2022
Further experiment verified some results and showed that JQHF has protected glomerular mesangial cells from lipopolysaccharide-induced inflammation by inhibiting expressions of IL6, TNF-α, and AKT1, and activating expressions of VEGFA. Based on network pharmacology, we explored the multi-component, multi-target, and multi-pathway characteristics of JQHF in treating CGN, and found that JQHF could act on IL6, TNF-α, VEGFA, and AKT1 to exert the effect of anti-CGN, which provided new ideas and methods for further research on the mechanism of JQHF in treating CGN.
- | sirolimus / Generic mfg.
Journal: Chronic Exposure to Palmitic Acid Down-regulates AKT in Beta-Cells through Activation of mTOR. (Pubmed Central) - Feb 16, 2022
In summary, we elucidated a novel mechanism for which lipid exposure may cause the dipole effects on beta-cell growth, where mTOR acts as a lipid sensor. These mechanisms can be novel targets for future therapeutic developments.
- || ezetimibe / Generic mfg.
Clinical, Journal, Real-world evidence: Impact of high neutrophil-to-lymphocyte ratio on the cardiovascular benefit of PCSK9 inhibitors in familial hypercholesterolemia subjects with atherosclerotic cardiovascular disease: Real-world data from two lipid units. (Pubmed Central) - Feb 16, 2022
Only FH subjects with low-NLR experienced a significant reduction of PWV after PCSK9-i. Our findings suggest a role of NLR in predicting PCSK9-i effect in FH subjects with ASCVD.
- | Journal: LncRNA PVT1 knockdown alleviated ox-LDL-induced vascular endothelial cell injury and atherosclerosis by miR-153-3p/GRB2 axis via ERK/p38 pathway. (Pubmed Central) - Feb 16, 2022
Our findings suggest a role of NLR in predicting PCSK9-i effect in FH subjects with ASCVD. PVT1 knockdown alleviated ox-LDL-induced vascular endothelial cell injury and atherosclerosis through miR-153-3p/GRB2 axis via ERK1/2 and p38 pathway.
- | Journal: Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways. (Pubmed Central) - Feb 16, 2022
Based on these findings, we further investigated the underlying molecular mechanisms and identified the NF-κB and ERK1/2 signaling pathways as potential targets of peiminine. In vivo, peiminine alleviated bone loss in an ovariectomized mouse model.
- || Clinical, Journal: Tenacious team, precarious patient: A phenomenological inquiry into interprofessional collaboration during ICU resuscitations. (Pubmed Central) - Feb 16, 2022
By understanding their lived experience, targeted interventions to improve interprofessional collaboration can be conceptualised and implemented. Findings will set pace for future evaluation research on interprofessional collaboration and patient outcomes during resuscitations.
- | Journal: miR-200a-3p represses osteogenesis of human periodontal ligament stem cells by targeting ZEB2 and activating the NF-κB pathway. (Pubmed Central) - Feb 16, 2022
miR-200a-3p repressed osteogenesis of hPDLSCs by targeting ZEB2 and activating the NF-κB pathway. This study may offer insights for periodontal tissue regeneration engineering.
- | Entresto (sacubitril/valsartan) / Novartis, ROVI Pharmaceuticals Laboratories
Journal: Association between ethnicity and degree of improvement in cardiac function following initiation of sacubitril/valsartan. (Pubmed Central) - Feb 16, 2022
Sacubitril/valsartan was associated with improved LVEF, NT-proBNP concentrations and quality of life in patients with symptomatic HFrEF on guideline recommended therapy. However, in our cohort, improvement of LVEF and quality of life might be attenuated in black patients, which warrants further investigation.
- || colchicine / Generic mfg.
Clinical, Retrospective data, Journal: The effect of vitamin K1 on arterial calcification activity in subjects with diabetes mellitus: a post hoc analysis of a double-blind, randomized, placebo-controlled trial. (Pubmed Central) - Feb 16, 2022
In individuals with diabetes mellitus, supplementation with 10 mg vitamin K1/d may prevent the development of newly calcifying lesions within the aorta and the coronary arteries as detected using 18F-NaF PET. Further long-term studies are needed to test this hypothesis.This trial was registered at anzctr.org.au as ACTRN12616000024448.
- | Preclinical, Journal: Leanness and Low Plasma Leptin in GPR17 Knockout Mice Are Dependent on Strain and Associated With Increased Energy Intake That Is Not Suppressed by Exogenous Leptin. (Pubmed Central) - Feb 16, 2022
The only difference between GPR17 +/- and GPR17 +/+ mice of the C57Bl/6 strain was that the body weight of the GPR17 -/- mice was lower than that of the GPR17 +/+ mice when the mice were fed on a standard chow diet. We propose that the absence of GPR17 raises sympathetic activity in mice of the 129 strain in response to a low plasma fuel supply, and that the consequent loss of body fat is partly mitigated by increased energy intake.
- || Xtandi (enzalutamide) / Pfizer, Astellas, Bausch Health
Clinical, Observational data, Journal: A European, prospective, observational study of enzalutamide in patients with metastatic castration-resistant prostate cancer: PREMISE. (Pubmed Central) - Feb 16, 2022
The most frequent TEAE across cohorts was fatigue. These data from unselected mCRPC patients in European, real-world, clinical-practice settings confirmed the benefits of enzalutamide previously shown in clinical trial outcomes, with safety results consistent with enzalutamide's known safety profile.
- || Clinical, Journal: Inequalities in enrollment of women and racial minorities in trials testing uric acid lowering drugs. (Pubmed Central) - Feb 16, 2022
These data from unselected mCRPC patients in European, real-world, clinical-practice settings confirmed the benefits of enzalutamide previously shown in clinical trial outcomes, with safety results consistent with enzalutamide's known safety profile. Our analysis shows that women and racial and ethnical minorities are underrepresented in controlled clinical trials testing SUA-lowering drugs, with similar pattern across drug classes.
- | Journal: MiR-130a-3p suppresses colorectal cancer growth by targeting Wnt Family Member 1 (WNT1). (Pubmed Central) - Feb 16, 2022
Dual-luciferase assay revealed WNT1 as a direct target of miR-130a-3p, and further the inhibitory effect of miR-130a-3p on c-myc and cyclin D1 was proved to be reversed by overexpressed WNT1. Collectively, miR-130a-3p inhibits CRC growth by directly targeting WNT1, and miR-130a-3p and WNT1 pathway-associated factors are defined as potential targets for CRC treatment.
- | Journal, Epigenetic controller: Transcription factor 3 (TCF3) combined with histone deacetylase 3 (HDAC3) down-regulates microRNA-101 to promote Burkitt lymphoma cell proliferation and inhibit apoptosis. (Pubmed Central) - Feb 16, 2022
We found that TCF3 can interact with HDAC3 and is enriched in the miR-101 promoter region. In conclusion, TCF3 combined with HDAC3 down-regulates the expression of miR-101, thereby promoting the proliferation of BL cells and inhibiting their apoptosis.
- | Journal: Interference with lysophosphatidic acid receptor 5 ameliorates oxidized low-density lipoprotein-induced human umbilical vein endothelial cell injury by inactivating NOD-like receptor family, pyrin domain containing 3 inflammasome signaling. (Pubmed Central) - Feb 16, 2022
Furthermore, MSU addition partially abrogated the inhibitory effects of LPAR5 deletion on the inflammation, oxidative stress and endothelium dysfunction of HUVECs. To conclude, we demonstrated that LPAR5 silencing alleviates ox-LDL-induced HUVECs injury by inhibiting NLRP3 inflammasome signaling.
- | Journal, IO biomarker: Bone mesenchymal stem cell-derived extracellular vesicles deliver microRNA-23b to alleviate spinal cord injury by targeting toll-like receptor TLR4 and inhibiting NF-κB pathway activation. (Pubmed Central) - Feb 16, 2022
The rescue experiments verified that after overexpression of TLR4, the activity of BV2 cells was decreased, the contents of IL-6, IL-1β, TNF-α, and p-p65 were increased, IL-10 was decreased, and SCI was aggravated. To conclude, The miR-23b delivered by BMSC-EVs targets TLR4 and inhibits the activation of NF-κB pathway, relieves the inflammatory response, so as to improve SCI in rats.
- | Brukinsa (zanubrutinib) / BeiGene
Preclinical, Journal: In vitro investigations into the roles of CYP450 enzymes and drug transporters in the drug interactions of zanubrutinib, a covalent Bruton's tyrosine kinase inhibitor. (Pubmed Central) - Feb 16, 2022
CYP3A inhibitors and inducers may impact systemic exposure of zanubrutinib. Dose adjustments may be warranted depending on the potency of CYP3A modulators.
- || Clinical, Journal: Antibiotic use and associated factors in adult outpatients from 2000 to 2019. (Pubmed Central) - Feb 16, 2022
The high use of antibiotics over the study period further reinforces the need of impactful interventions, in order to improve the rational use of antibiotics and to reduce the risks of antimicrobial resistance. The differences outlined should be considered when monitoring and planning these interventions.
- | Victoza (liraglutide) / Novo Nordisk
Journal: Liraglutide blocks the proliferation, migration and phenotypic switching of Homocysteine (Hcy)-induced vascular smooth muscle cells (VSMCs) by suppressing proprotein convertase subtilisin kexin9 (PCSK9)/ low-density lipoprotein receptor (LDLR). (Pubmed Central) - Feb 16, 2022
Liraglutide blocked the proliferation, migration and phenotypic switching of Hcy-induced VSMCs by suppressing PCSK9/LDLR. This finding provided the basis for the future application of liraglutide as an effective drug for therapeutic strategy in targeting AS.
- | dexamethasone / Generic mfg.
Journal: Oxygen and Steroids Affect the Regulatory Role of Natriuretic Peptide Receptor-C on Surfactant Secretion by Type II Cells. (Pubmed Central) - Feb 16, 2022
DEX markedly reduced AEC2 NPR-C expression, and pregnant ewes treated with betamethasone showed reduced ANP in fetal sheep lung fluid. These data suggest that elevated O downregulates AEC2 NPR-C, and that steroid-mediated NPR-C downregulation in neonatal lungs may provide a novel mechanism for their effect on perinatal surfactant production.
- | Journal: FJU-C28 inhibits the endotoxin-induced pro-inflammatory cytokines expression via suppressing JNK, p38 MAPK and NF-κB signaling pathways. (Pubmed Central) - Feb 16, 2022
FJU-C28 also reduced neutrophil infiltration in the interstitium, lung damage and circulating levels of IL-6 and RANTES in mice with systemic inflammation. In conclusion, these findings suggest that FJU-C28 possesses anti-inflammatory activities to prevent endotoxin-induced lung function decrease and lung damages by down-regulating proinflammatory cytokines including IL-6 and RANTES via suppressing the JNK, p38 MAPK and NF-κB signaling pathways.
- | Journal: Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis. (Pubmed Central) - Feb 16, 2022
Furthermore, in vivo assays show that knockout of OTUB2 inhibits tumor growth in mice. Taken together, these findings reveal the critical role of OTUB2 in the regulation of glycolysis and illustrate the molecular mechanism underlying its role as a negative regulator of PKM2 ubiquitination in CRC, establishing a bridge between OTUB2-regulated PKM2 ubiquitination and altered metabolic patterns in CRC and suggesting that OTUB2 is a promising target for CRC treatment.
- | Journal: Long non-coding RNA LINC00958 promotes colorectal cancer progression by enhancing the expression of LEM domain containing 1 via microRNA miR-3064-5p. (Pubmed Central) - Feb 16, 2022
Our analyses have shown that LINC00958 could facilitate the progression of colorectal cancer by sponging miR-3064-5p and releasing LEMD1, leading to the activation of the PI3K/AKT pathway. Thus, LINC00958 may be considered as an effective biomarker for the treatment of colorectal cancer.
- | XAV-939 / Novartis
Journal: MicroRNA-15a-5p plays a role in osteogenic MC3T3-E1 cells differentiation by targeting PDCD4 (programmed cell death 4) via Wnt/β-catenin dependent signaling pathway. (Pubmed Central) - Feb 16, 2022
In conclusion, miR-15a-5p induced differentiation of osteoblasts and mineralization by modulating osteoblast differentiation factors, mainly OSX, ALP, OCN, and RUNX2, by inhibiting PDCD4 and Wnt signaling pathways. This study provides a modality for the future use of miR-15a-5p in the treatment and prevention of osteoporosis.
- | Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Journal: Dapagliflozin Reduces Urinary Albumin Excretion by Downregulating the Expression of cAMP, MAPK, and cGMP-PKG Signaling Pathways Associated Genes. (Pubmed Central) - Feb 16, 2022
Gene ontology annotation enrichment analysis showed that DAP mainly affected the expression of integral component of membrane- and cell junction-related genes, while the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that DAP primarily downregulated the expression of gene clusters associated with cyclic adenosine monophosphate, mitogen-activated protein kinase, and cyclic guanosine monophosphate-protein kinase G signaling pathways, which play critical roles in the progression of DN. Our results shed light on the mechanism by which DAP controls DN progression and provide a theoretical basis for the clinical treatment of DN.
- | Journal: Exosomal lncRNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1)contributes to the progression of allergic rhinitis via modulating microRNA-511/Nuclear Receptor Subfamily 4 Group A Member 2 (NR4A2) axis. (Pubmed Central) - Feb 16, 2022
In conclusion, our data revealed that exosomal NEAT1 contributed to the pathogenesis of AR through the miR-511/NR4A2 axis. These findings might offer novel strategies for the prevention and treatment of AR.
- | gefitinib / Generic mfg.
Journal: DARPP-32 promotes ERBB3-mediated resistance to molecular targeted therapy in EGFR-mutated lung adenocarcinoma. (Pubmed Central) - Feb 16, 2022
In mice, DARPP-32 ablation sensitizes gefitinib-resistant xenografts to EGFR TKIs, while DARPP-32 overexpression increases gefitinib-refractory LUAD progression in gefitinib-sensitive lung tumors. We introduce a DARPP-32-mediated, ERBB3-dependent mechanism the LUAD cells use to evade EGFR TKI-induced cell death, potentially paving the way for the development of therapies to better combat therapy-refractory LUAD progression.
- | Journal: OLFM4-RET fusion is an oncogenic driver in small intestine adenocarcinoma. (Pubmed Central) - Feb 16, 2022
Our study suggests that OLFM4-RET is an oncogenic driver of small intestine tumorigenesis. Therefore, the small intestine adenocarcinoma patients with OLFM4-RET fusion may benefit from treatment with RET kinase inhibitor.
- || Review, Journal: Nuclear receptors of NR1 and NR4 subfamilies in the regulation of microglial functions and pathology. (Pubmed Central) - Feb 16, 2022
On the other hand, increasing lines of evidence suggest that the stimulation of NR4 subfamily members of nuclear receptors such as Nur77 and Nurr1 also regulates microglial functions and alleviates neuropathological events in several disease models. Further advancement of these research fields may prove novel therapeutic opportunities.
- | clozapine / Generic mfg.
Journal: Chemogenetic stimulation of the G pathway in astrocytes suppresses neuroinflammation. (Pubmed Central) - Feb 16, 2022
We found that astrocyte G -DREADD stimulation using clozapine N-oxide (CNO) inhibits neuroinflammation, as characterized by decreased levels of proinflammatory cytokines, glial activation, and cognitive impairment in mice...Similarly, in vitro calcium imaging showed that activation of the astrocytic G pathway attenuated intracellular calcium transients triggered by LPS treatment, suggesting a positive correlation between enhanced calcium transients and the inflammatory phenotype of astrocytes observed in the inflamed brain. Taken together, our results indicate that the astrocytic G pathway plays an inhibitory role in neuroinflammation, providing an opportunity to identify potential cellular and molecular targets to control neuroinflammation.
- || goshajinkigan (TJ-107) / Tsumura
Review, Journal: Goshajinkigan attenuates paclitaxel-induced neuropathic pain via cortical astrocytes. (Pubmed Central) - Feb 16, 2022
Finally, the inhibition of S1 astrocytes by an astrocyte-toxin L-alpha-aminoadipic acid abolished the PCX-induced neuropathy. Our findings suggest that astrocytes in the S1 cortex would play an important role in the pathogenesis of PCX-induced neuropathy and are a potential target for its treatment.
- | Journal: SoxE group transcription factor Sox8 promotes astrocytic differentiation of neural stem/precursor cells downstream of Nfia. (Pubmed Central) - Feb 16, 2022
In contrast to Nfia, Sox8 did not induce DNA demethylation of an astrocyte-specific marker gene, glial fibrillary acidic protein (Gfap), but instead associated with LIF downstream transcription factor STAT3 through transcriptional coactivator p300, explaining how Sox8 expression further facilitated LIF-induced Gfap expression. Taken together, these results suggest that Sox8 is a crucial Nfia downstream transcription factor for the astrocytic differentiation of NS/PCs in the developing brain.
- | temozolomide / Generic mfg.
Journal: Cytotoxicity Effect of Quinoin, Type 1 Ribosome-Inactivating Protein from Quinoa Seeds, on Glioblastoma Cells. (Pubmed Central) - Feb 16, 2022
Moreover, considering that common conventional glioblastoma multiforme (GBM) cell lines are genetically different from the tumors from which they derive, the cytotoxicity of quinoin was subsequently tested towards primary cells NULU and ZAR (two cell lines established from patients' gliomas), also in combination with the chemotherapeutic agent temozolomide (TMZ), currently used in glioblastoma treatment...Interestingly, primary cells treated with quinoin in combination with TMZ were more sensitive to the treatment. Overall, our data highlight that quinoin could represent a novel tool for glioblastoma therapy and a possible adjuvant for the treatment of the disease in combination with TMZ, alone or as possible immunoconjugates/nanoconstructs.
- || Review, Journal: Shiga Toxins as Antitumor Tools. (Pubmed Central) - Feb 16, 2022
These properties have led to many attempts to develop Stxs as tools for biomedical applications, such as cancer treatment or imaging, and several engineered Stxs are currently being tested. We provide here an overview of these studies.
- | Journal: Proteomic and phosphoproteomic analyses identify liver-related signaling in retinal pigment epithelial cells during EMT. (Pubmed Central) - Feb 16, 2022
Induction by co-treatment with transforming growth factor β and tumor necrosis factor alpha (TGNF) or enzymatic dissociation perturbs signaling in many of the same pathways, with striking similarity in the respective phosphoproteomes at 1 h. Liver hyperplasia and hepatocyte growth factor (HGF)-MET signaling exhibit the highest overall enrichment. We also observe that HGF and epidermal growth factor signaling, two cooperative pathways inhibited by EMT induction, regulate the RPE transcriptional profile.
- | Journal: NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions. (Pubmed Central) - Feb 16, 2022
This is highly relevant in the clinic, as the different degrees of engagement of the NKG2A-HLA-E checkpoint in hepatocellular carcinoma, glioblastoma, and non-small cell lung cancer directly impact patients' overall survival. These findings open avenues for developing combined cellular and immunologic anticancer therapies.
- | Journal, Pan tumor: Pan-cancer analysis of non-coding transcripts reveals the prognostic onco-lncRNA HOXA10-AS in gliomas. (Pubmed Central) - Feb 16, 2022
Loss- and gain-of-function studies in patient-derived glioma cells, organoids, and xenograft models identify HOXA10-AS as a potent onco-lncRNA that regulates cell proliferation, contact inhibition, invasion, Hippo signaling, and mitotic and neuro-developmental pathways. Our study underscores the pan-cancer potential of the non-coding transcriptome for identifying biomarkers and regulators of cancer progression.
- | Preclinical, Journal: Hippocampal and thalamic afferents form distinct synaptic microcircuits in the mouse infralimbic frontal cortex. (Pubmed Central) - Feb 16, 2022
These results show a prominent bias among long-range hippocampal and thalamic afferent systems in their targeting to specific sets of frontal cortical neurons. Moreover, they suggest the presence of two distinct local microcircuits that control how different inputs govern frontal cortical information processing.
- | Journal: ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes. (Pubmed Central) - Feb 16, 2022
We also find that recombinant DWnt-5 can bind Drosophila ROR and RYK orthologs despite lacking an acyl chain. Alongside analyses of WNT/receptor interaction sites, our structures provide further insight into how WNTs may recruit RTK co-receptors into signaling complexes.
- | Journal: Marker-free lineage tracing reveals an environment-instructed clonogenic hierarchy in pancreatic cancer. (Pubmed Central) - Feb 16, 2022
This means that the microenvironment is dominant in defining the clonogenic activity of PDAC cells. Indeed, manipulating the stroma by Hedgehog pathway inhibition alters the tumor growth mode, revealing that tumor-stroma crosstalk shapes tumor growth dynamics and clonal architecture.
- | Journal, IO biomarker: Targeting TREM2 on tumor-associated macrophages enhances immunotherapy. (Pubmed Central) - Feb 16, 2022
In an aggressive orthotopic ovarian cancer model, anti-TREM2 mAb therapy drives potent anti-tumor immunity. These results highlight TREM2 as a highly attractive target for immunotherapy modulation in individuals who are refractory to CPI therapy and likely have a TAM-rich tumor microenvironment.