- |||||||||| salirasib (KD 032) / Kadmon, Ono Pharma, Koselugo (selumetinib) / Merck (MSD), AstraZeneca, Verzenio (abemaciclib) / Eli Lilly
[VIRTUAL] Biology of KRAS Targeting Agents (Scientific Program Auditorium) - Dec 4, 2020 - Abstract #IASLCWCLC2020IASLC_WCLC_212;
Salirasib, farnesyl thiosalicylic acid, inhibits prenylated protein methyltransferase (PPMTase) with potent in vitro activity, including against KRAS; however, failed in a phase II trial12...For example, the phase 3 trial of MEK inhibitor selumetinib 13 did not show its benefit...Based on these experiments, abemaciclib, a CDK4/6 inhibitor, plus erlotinib was compared with erlotinib in patients with KRAS mutation in a phase III trial...Aguirre AJ, et al.: Cold Spring Harb Perspect Med 8, 2018 16. Goldman JW, et al.: Front Oncol 10:578756, 2020
- |||||||||| simvastatin / Generic mfg.
Journal: Simvastatin ameliorates altered mechanotransduction in uterine leiomyoma cells. (Pubmed Central) - Dec 2, 2020
The results of this study suggest a possible therapeutic role for simvastatin to restore the altered state of mechanotransduction signaling in leiomyoma. Collectively, the findings are aligned with previous epidemiologic and other reports and support the need for clinical trials.
- |||||||||| Journal: Bottom-up engineering of cell-laden hydrogel microfibrous patch for guided tissue regeneration. (Pubmed Central) - Nov 27, 2020
After characterization of the microfibrous patch, the behavior of embedded human mesenchymal stem cells (hMSCs) was evaluated. Microfibers of oxidized alginate modified with integrin-binding ligands provided a suitable 3D cellular microenvironment, supporting hMSCs survival and stimulating the production of endogenous extracellular matrix proteins, such as fibronectin and collagen Type I. Collectively, these features make the proposed microfibrous structures stand out as promising 3D scaffolds for regenerative medicine.
- |||||||||| Journal: Osteopontin in Bone Metabolism and Bone Diseases. (Pubmed Central) - Nov 27, 2020
As expected, the functions of OPN in the bone have become a research hotspot. In this article, we try to decipher the mechanism of OPN-regulated bone metabolism and bone diseases.
- |||||||||| Journal: Transcriptomic changes during TGF-β-mediated differentiation of airway fibroblasts to myofibroblasts. (Pubmed Central) - Nov 14, 2020
We have found a significant number of genes that are altered after TGF-β induced transdifferentiation of WI-38 fibroblasts into myofibroblasts, many of which were expected or predicted. We also identified novel genes and pathways that were affected after TGF-β treatment, suggesting additional pathways are activated during the transition between fibroblasts and myofibroblasts and may contribute to the asthma phenotype.
- |||||||||| Journal, PD(L)-1 Biomarker, IO Biomarker: Enhanced Immunomodulation in Inflammatory Environments Favors Human Cardiac Mesenchymal Stromal-Like Cells for Allogeneic Cell Therapies. (Pubmed Central) - Nov 12, 2020
While the application of blocking antibodies against both PD-1 ligands did not affect the immunomodulation by hAACs, 1-methyl-L-tryptophan as specific inhibitor of IDO was able to restore proliferation and to lower apoptosis of T cells. In conclusion, hAACs represent a cardiac-derived mesenchymal stromal-like cell type with a high potential for the application in an allogeneic setting, since they do not trigger T cell responses and even increase their immunomodulatory potential in inflammatory environments.
- |||||||||| Journal: Coagulation Factor XIII-A Subunit Missense Mutation in the Pathobiology of Autosomal Dominant Multiple Dermatofibromas. (Pubmed Central) - Nov 12, 2020
In addition, both the α4β1 inhibitors and the mutation of the FXIII-A Isoleucine-Leucine-Aspartate-Threonine (ILDT) motif prevented Lys679Met FXIII-A-dependent proliferation and collagen synthesis of fibroblasts. Our data suggest that the Lys679Met mutation may leads to a conformational change in the FXIII-A protein that enhances α4-integrin binding and provide insight into an unexpected role for FXIII-A in the pathobiology of familial dermatofibroma.
- |||||||||| tamoxifen / Generic mfg.
Journal: Requirement of β1 integrin for endothelium-dependent vasodilation and collateral formation in hindlimb ischemia. (Pubmed Central) - Nov 12, 2020
Using high frequency ultrasound, we demonstrated that β1 integrin-blocking antibody or endothelial cell-specific depletion of β1 integrin attenuated FMD of the femoral artery, and blocking of β1 integrin function did not further decrease FMD in eNOS-deficient mice. Our data suggest that endothelial β1 integrin is required for both acute and chronic widening of the arterial lumen in response to hindlimb ischemia, potentially via functional interaction with eNOS.
- |||||||||| Review, Journal: Integrin Signaling in Glioma Pathogenesis: From Biology to Therapy. (Pubmed Central) - Nov 12, 2020
In this review we provide an overview of the involvement of integrin signaling in glioma pathogenesis, formation of the tumor niche and brain tissue infiltration. We will summarize up-to-date therapeutic strategies for gliomas focused on interference with integrin ligand-receptor signaling.
- |||||||||| Journal: Differential Expression of Integrin β1 in Two Brain Injury Models of Rats. (Pubmed Central) - Nov 12, 2020
At the same time points after injury, the differences in the positive expression of integrin β1 between the linear acceleration injury group and the rotation acceleration injury group in the occipital strike point and thalamus had no statistical significance （ P>0.05）, but the differences in the expression of integrin β1 in the frontal lobe and brain stem had statistical significance （P<0.05）. Conclusion The characteristics of positive expression of integrin β1 in brain tissue can be used to infer the strike point and the manner of injury and has application value for the reconstruction of craniocerebral injury process.
- |||||||||| Lamprene (clofazimine) / Novartis
Journal: Acoustic tweezing cytometry for mechanical phenotyping of macrophages and mechanopharmaceutical cytotripsy. (Pubmed Central) - Nov 7, 2020
Clofazimine, an FDA-approved antibiotic, accumulates and precipitates as rod-shaped, crystal-like drug inclusions within macrophage lysosomes...Most notably, application of ultrasound pulses of longer duration and higher amplitude in ATC actuated the integrin-bound microbubbles to mobilize the crystal-like drug inclusions inside macrophages, turning the rod-shaped drug inclusions into intracellular microblender that effectively destructed the cells. This phenomenon of acoustic mechanopharmaceutical cytotripsy may be exploited for ultrasound activated, macrophage-directed drug release and delivery.
- |||||||||| fluorouracil topical / Generic mfg.
[VIRTUAL] Ing4 Deficiency Reprograms Multipotent Progenitor Cells to Confer Self-Renewal Capabilities (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2299;
Finally, after 5-FU treatment, levels of MPPs in WT mice were similar pre- and post-treatment...These findings suggest Ing4 is a critical regulator of hematopoiesis, and these data provide important clues for further characterization of the pathways and functions of Ing4. Our data show that Ing4 deficiency promotes stem cell-like properties in MPPs, suggesting it has crucial regulatory functions in both stem cell self-renewal and maintenance.
- |||||||||| hydroxyurea / Generic mfg.
[VIRTUAL] Genetic Association of Clinical Complications for Genes Differentially Expressed in Reticulocytes of Sickle Cell Anemia (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_2173;
For hemolysis and hemoglobin concentration, the covariates included age, gender, β globin genotype severity, alpha thalassemia, hydroxyurea treatment, recent blood transfusion, and population stratification...Discussion Our results reveal enrichment of genetic association with vaso-occlusive and hemolytic complications in gene functional categories that showed altered expression in sickle reticulocytes. Future study is needed to validate these associations.
- |||||||||| EP-300 / Esperance Pharma
[VIRTUAL] Whole-Genome Analysis of Adult T-Cell Leukemia/Lymphoma (Channel 7 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_1623;
In particular, inactivation of EP300 and immune-related molecules, such as HLA-A, HLA-B, and CD58, were associated with an increased number of mutations and SVs, especially deletions and tandem duplications...In summary, our WGS analysis not only identifies novel somatic alterations but also extends the overview of ATL genome. We also propose a new molecular classification of ATL, with its clinical relevance, which can lead to the future improvement of patient management.
- |||||||||| Avastin (bevacizumab) / Roche
[VIRTUAL] Role of c-Met/β1 integrin complex in the metastatic cascade () - Oct 24, 2020 - Abstract #SNO2020SNO_937;
We previously identified a structural complex between receptor tyrosine kinase c-Met and β1 integrin in metastases that form under certain biological and therapeutic inducers, including bevacizumab...OS2966, a therapeutic B1 integrin blocking antibody, disrupted c-Met/β1 binding as well, and decreased invasion, mesenchymal gene expression, and mesenchymal morphology of breast cancer cells...Thus, our research suggests the c-Met/β1 complex drives breast cancer cell intravasation and preferential affinity for bone tissue-specific matrix. Pharmacological targeting of the complex may prevent metastases, particularly osseous metastases.
- |||||||||| [VIRTUAL] Zika Virus Targets Glioblastoma Stem Cells through a SOX2-Integrin αvβ5 Axis () - Oct 24, 2020 - Abstract #SNO2020SNO_87;
These findings indicate potential therapeutic value of this FDA-approved drug if repurposed for GBM patients. Collectively, our results reveal that ZIKV infection of GSCs is mediated by integrin αvβ5 leading to SOX2 expression which negatively regulates antiviral immunity thereby facilitating ZIKV infection.
- |||||||||| Journal: Non-toxic freezing media to retain the stem cell reserves in adipose tissues. (Pubmed Central) - Jul 21, 2020
Alizarin Red S staining for osteogenesis revealed that FM1 and FM4 media displayed superior differentiation in comparison to other tested media. Measurement of adipogenic and osteogenic gene expression by qRT-PCR provided similar outcomes and indicated that FM4 CPA media comparable with FM1 for adipogenesis and osteogenesis.
- |||||||||| Journal: Filopodia play an important role in the trans-mesothelial migration of ovarian cancer cells. (Pubmed Central) - Apr 28, 2020
Conversely, downregulation of cortactin or TKS5 or treatment with the MMP inhibitor GM6001 or the N-WASP inhibitor wiskostatin did not have any effect on cancer cell trans-mesothelial migration. These results suggest that filopodia, but not lamellipodia or invadopodia, play an important role in the trans-mesothelial migration of ovarian cancer cells.
- |||||||||| Journal: Evaluation of CD49e as a distinguishing marker for human articular cartilage derived chondroprogenitors. (Pubmed Central) - Apr 23, 2020
These results suggest that filopodia, but not lamellipodia or invadopodia, play an important role in the trans-mesothelial migration of ovarian cancer cells. As the specificity of CD49e is questionable, there is a pressing need for a specific differentiating marker, to isolate a pure population of chondroprogenitors, as this cell type shows inherent chondrogenesis and reduced hypertrophy, both requisites for cartilage repair.
- |||||||||| Preclinical, Journal: Human olfactory mesenchymal stromal cells co-expressing horizontal basal and ensheathing cell proteins in culture. (Pubmed Central) - Mar 30, 2020
As the specificity of CD49e is questionable, there is a pressing need for a specific differentiating marker, to isolate a pure population of chondroprogenitors, as this cell type shows inherent chondrogenesis and reduced hypertrophy, both requisites for cartilage repair. Mesenchymal and olfactory precursor proteins were downregulated by serum-free medium and promoted differentiation of mesenchymal stromal cells into neurons and astroglial cells.
- |||||||||| Journal: A Micropeptide MIAC Inhibits HNSCC Progression by Interacting with Aquaporin 2. (Pubmed Central) - Mar 17, 2020
Mechanistically, MIAC directly interacts with AQP2 (Aquaporin 2) to inhibit actin cytoskeleton by regulating the SEPT2 (Septin 2)/ITGB4 (Integrin Beta 4), and ultimately suppress tumor growth and metastasis of HNSCC. Collectively, the mechanism investigation and evaluation of MIAC activity in vivo and in vitro highlight that MIAC plays an important role in HNSCC tumorigenesis.
- |||||||||| Journal: Androgen Indirectly Regulates Gap Junction Component Connexin 43 via Wilms Tumor-1 in Sertoli Cells. (Pubmed Central) - Dec 8, 2019
Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) demonstrated that WT1 occupied Cx43 promoter in Sertoli cells, suggesting WT1 as an intermediate molecule in regulation of Cx43. Finally, we revealed a regulatory pattern of Cx43 by androgen in Sertoli cells, and the Sertoli cells in germ cell depleted microenvironment were sensitive to androgen signal, which enhances the understanding of the mechanism of spermatogenesis.
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