- |||||||||| doxycycline / Generic Mfg.
Clinical, Journal: Mediterranean spotted fever in the elderly: a prospective cohort study. (Pubmed Central) - Nov 19, 2019
Some clinical manifestations occurred with different frequencies in the elderly compared with younger patients. Single-day doxycycline therapy is an effective and well-tolerated treatment for MSF in elderly patients.
- |||||||||| doxycycline / Generic Mfg.
Journal: Expanded table: drugs for prophylaxis of malaria. (Pubmed Central) - Nov 18, 2019
Single-day doxycycline therapy is an effective and well-tolerated treatment for MSF in elderly patients. No abstract available
- |||||||||| ciprofloxacin / Generic Mfg., Xifaxan (rifaximin) / Alfa Wassermann, Bausch Health, Norgine, doxycycline / Generic Mfg.
Journal: Advice for travelers. (Pubmed Central) - Nov 18, 2019
No abstract available No abstract available
- |||||||||| doxycycline / Generic Mfg.
Review, Journal: Tetracycline repurposing in neurodegeneration: focus on Parkinson's disease. (Pubmed Central) - Nov 14, 2019
In addition, we examine the hypothesis that the anti-inflammatory activities of tetracyclines regulate inflammasome signaling. Based on their excellent safety profiles in humans from their use for over 50 years as antibiotics, we propose the repurposing of tetracyclines, a multitarget antibiotic, to treat Parkinson's disease.
- |||||||||| doxycycline / Generic Mfg.
Journal: In Vitro Screen to Identify Silent but Activatable (S/A) Integration Sites for a Tetracycline-Inducible Transgene in Mice. (Pubmed Central) - Nov 14, 2019
The procedure requires (1) an embryonic stem (ES) cell line (germline competent) expressing rtTA from the Rosa-26 locus and (2) construction of a Tet-inducible transgene. The transgene contains the tet-O promoter followed by the gene of interest linked to a βgeo gene (a fusion between lacZ and neo) through an internal ribosomal entry site (IRES) sequence, which allows the initiation of translation in a cap-independent manner.
- |||||||||| doxycycline / Generic Mfg.
Journal: MYC and RAS are unable to cooperate in overcoming cellular senescence and apoptosis in normal human fibroblasts. (Pubmed Central) - Nov 14, 2019
We conclude that MYC and RAS are unable to cooperate in overcoming senescence and apoptosis in normal human fibroblasts even after depletion of p53, indicating that additional oncogenic events are required to abrogate these fail-safe mechanisms and pave the way for cellular transformation. These findings have implications for our understanding of the transformation process in human cells.
- |||||||||| ceftriaxone / Generic Mfg., doxycycline / Generic Mfg.
Journal: Management of Central Nervous System Infections, Vientiane, Laos, 2003-2011. (Pubmed Central) - Nov 14, 2019
No clinical or laboratory variables could guide antibiotic selection. We conclude that high-dependency units and first-line treatment with ceftriaxone and doxycycline for suspected CNS infections could improve patient survival in Laos.
- |||||||||| doxycycline / Generic mfg.
Enrollment closed, Trial completion date, Trial primary completion date: Lipidome and Microbiome Profile of the Eye in Rosacea (clinicaltrials.gov) - Nov 13, 2019
P1, N=30, Active, not recruiting,
We conclude that high-dependency units and first-line treatment with ceftriaxone and doxycycline for suspected CNS infections could improve patient survival in Laos. Recruiting --> Active, not recruiting | Trial completion date: Sep 2019 --> Jan 2020 | Trial primary completion date: Sep 2019 --> Jan 2020
- |||||||||| ceftriaxone / Generic Mfg., doxycycline / Generic Mfg., Garamycin (gentamicin sulfate) / Generic Mfg.
Journal: Antimicrobial Resistance of Salmonella Isolates Recovered from Chickens Sold at Retail Outlets in Trinidad. (Pubmed Central) - Nov 11, 2019
All the 135 Salmonella isolates exhibited multidrug resistance patterns. The high frequency of resistance to seven antimicrobial agents (erythromycin, streptomycin, ceftiofur, doxycycline, kanamycin, tetracycline, and ampicillin), some used in the poultry industry, coupled with the occurrence of multidrug resistance, may have potential therapeutic implications for broiler farmers in Trinidad.
- |||||||||| doxycycline / Generic Mfg.
Review, Journal: The Rickettsioses: A Practical Update. (Pubmed Central) - Nov 10, 2019
Reactive antibodies are seldom present during early illness, so testing should be performed on both acute-phase and convalescent-phase sera. Doxycycline is the treatment of choice.
- |||||||||| doxycycline / Generic Mfg.
Journal: Increased arterial pressure in mice with overexpression of the ADHD candidate gene calcyon in forebrain. (Pubmed Central) - Nov 8, 2019
Silencing the transgene with doxycycline normalized BP in CalOE mice, whereas challenging the mice with 4% high salt diet for 12 days exacerbated the MAP differences between CalOE and tTA mice...Taken together, our data suggest that upregulation of calcyon in forebrain could increase BP via alterations in noradrenergic transmission and increased oxidative stress during high salt challenge. Overall, this study reveals that calcyon could be a novel neural regulator of BP raising the possibility that it could play a role in the development of vascular abnormalities.
- |||||||||| doxycycline / Generic Mfg.
Review, Journal: Spinal Aneurysmal Bone Cysts (ABCs): Optimal Management. (Pubmed Central) - Nov 7, 2019
SAE is a useful adjunct to reduce intraoperative bleeding, but this study suggests that it only modestly improves recurrence rates. Newer techniques including bisphosphonate and doxycycline administration offer potential benefits, but their efficacy requires further investigation.
- |||||||||| doxycycline / Generic Mfg.
Journal: Factors Associated With Survival and Return to Function Following Synovial Infections in Horses. (Pubmed Central) - Nov 7, 2019
Horses treated with doxycycline were less likely to return to function (OR 0.39, 95% CI 0.19-0.8, P = 0.031)...The likelihood of return to function is lower than for survival. The findings of this study, combined with relevant antimicrobial stewardship practices, can be used as a part of evidence-based decision-making when veterinarians are treating horses with SI.
- |||||||||| doxycycline / Generic mfg.
Multiple Myeloma Pathogenesis: The Role of Junb in Bone Marrow Angiogenesis (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6087;
Finally, treatment with doxycycline effectively inhibited JunB levels and consistently reduced microvessel density in immunodeficient NSG mice inoculated with TetR-shJUNB/ MM.1S, but not TetR-SCR/ MM.1S. In conclusion, our findings demonstrate a pivotal role of JUNB in MM BM angiogenesis; they thereby provide further evidence that JUNB is a promising therapeutic target particularly in early MM.
- |||||||||| doxycycline / Generic mfg.
P53 Pathway Activation Mediated High c-MAF Expression Is Associated with Overall and Post-Progression Survival in Multiple Myeloma (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6076;
Although the mechanism of high expression of c-MAF and MAFB has previously been reported in IgH translocation, the relationship between c-MAF and drug resistance remains to be determined. The induction of c-MAF expression by tumor suppressor gene p53 is suggested to be a mechanism underlying poor prognosis of MM with t (14;16), and suppressing c-MAF expression with chemotherapeutic drugs might prevent emergence of drug resistance in residual tumor cells.
- |||||||||| doxycycline / Generic mfg.
The Clinical and Functional Relevance of the Transforming AKT E17K Mutation in T-ALL (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5529;
For this study, we used doxycycline-inducible SUP-T1 cell lines that overexpress wild type AKT or mutant AKTE17K molecules...Indeed, SUP-T1 cells expressing wild type AKT or mutant AKTE17K are equally sensitivity to the ATP-competitive AZD5363 inhibitor, but AKTE17K cells display reduced sensitivity to the MK2206 allosteric inhibitor compared to AKT wild type cells...Since no differences in NR3C1 phosphorylation or nuclear shuttling were observed in our model, we hypothesize other mechanisms underlie the provoked steroid resistance by AKT wild type overexpression. To identify these novel mechanisms, we are currently performing an unbiased phospho-protein array to identify differentially phosphorylated AKT substrates.
- |||||||||| doxycycline / Generic mfg.
Gfi1 Upregulates c-Myc Expression and Promotes c-Myc-Driven Cell Proliferation (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5492;
Interestingly, the levels of endogenous c-Myc mRNA and protein were augmented upon induction of Gfi1 expression in Ba/F3 and Burkitt lymphoma Ramos cells transduced with the doxycycline-inducible Gfi1 lentiviral construct, but reduced in Gfi1-knocked down human leukemic HL60 and U937 cells...Thus, in addition to its role in c-Myc-mediated transcriptional repression, Gfi1 upregulates c-Myc expression at both mRNA and protein levels, leading to enhanced expression of c-Myc-activated genes and augmented cell proliferation driven by c-Myc. Together, these data may reveal a novel mechanism by which Gfi1 collaborates with c-Myc in lymphomagenesis.
- |||||||||| doxycycline / Generic mfg.
Development of a Human in Vitro Cell Model for Haemophilia a (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5348;
Methods First, we immortalized primary human hepatic sinusoidal endothelial cells (HHSEC), the natural cell of FVIII synthesis in humans, by lentiviral transduction of a doxycycline-inducible SV40-Large T oncogene...Conclusion By immortalization and transduction of HHSECs we generated a human haemophilia A cell line model based on mutagenesis of the endogenous genetic FVIII locus in the cell line, which mainly accounts for FVIII production in humans. This cell model will be used to study FVIII synthesis, signaling and processing and, in addition, aids in the development of new strategies for haemophilia A gene therapy or new FVIII preparations.
- |||||||||| doxycycline / Generic mfg.
TET Dioxygenase Inhibition As a Therapeutic Strategy in TET2 Mutant Myeloid Neoplasia (W311EFGH, Level 3 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5193;
Doxycycline inducible expression of IDH1MT led to profound growth inhibition of both a natural TET2MT cell line SIG-M5 and engineered TET2-/- K562, while the effect to parental K562 was mild (Fig.B-E)...TETi treatment selectively restricted the proliferative advantage of Tet2MT HSC compared to vehicle control where, as expected, TET2 mutant clones took over the WT cells. In clinical applications, TET inhibitors may constitute a new class of agents to be used in a targeted fashion in TET2 mutant neoplasia.
- |||||||||| doxycycline / Generic mfg.
Mutant U2AF1S34F and U2AF1Q157P Induce Distinct RNA Splicing and Hematopoietic Phenotypes In Vivo (Tangerine 2 (WF2), Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5059;
To study the impact of U2AF1Q157P expression on splicing and hematopoiesis in vivo, we created a doxycycline (DOX)-inducible (“Tet-On”) transgenic mouse that expresses mutant U2AF1Q157P and is isogenic to our previously reported U2AF1S34F and U2AF1WT transgenic mice...In aggregate, hematopoietic expression of U2AF1Q157P causes a multi-lineage competitive disadvantage of BM stem cells and expanded myeloid progenitors in the non-competitive transplant setting, like U2AF1S34F. However, PB counts and lineage distribution are not affected, indicating that the two common U2AF1 mutants, Q157P and S34F, are associated with different hematopoietic phenotypes and alterations to splicing, and may have different roles in MDS pathogenesis.
- |||||||||| imatinib / Generic mfg., doxycycline / Generic mfg.
NF-κB-Dependent Activation of the Proteasome Components, PSMD1 and PSMD3, As a Mechanism of Resistance to Imatinib (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_4108;
Our data also suggest that specific targeting of the ubiquitin proteasome system through either PSMD1 or PSMD3 may be a novel strategy to restore TKI sensitivity in patients with BCR-ABL1-independent TKI resistance. Future studies will address the non-canonical functions of STAT3 in TKI resistance.
- |||||||||| doxycycline / Generic mfg.
Marcks Is a Critical Downstream Mediator of IL-1-Driven AML Progression (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_3855;
IL-1 stimulation of AML progenitors increases MARCKS phosphorylation. MARCKS promotes AML progression by increasing the cellular growth, survival, and cell cycle progression of leukemic cells.
- |||||||||| doxycycline / Generic mfg.
Adult Hematopoietic Stem and Progenitor Cell Maintenance Requires Histone Variant H3.3 Regulation By Hira (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_3636;
We then assessed gene expression changes in Hira cKO HSPCs in a doxycycline-inducible H2B-GFP background (Mx1-Cre; Hirafl/fl; R26-M2rtTa; TetOP-H2B-GFP) to distinguish between the gene expression changes caused by Hira loss before and after cell division...This study identifies a novel epigenetic mechanism required for adult HSPC maintenance and elucidates a previously unappreciated regulator of normal hematopoietic homeostasis. Further understanding how Hira-mediated H3.3 regulation maintains adult HSPCs will provide greater depth to our current understanding of the epigenetic regulators essential for hematopoiesis.
- |||||||||| doxycycline / Generic mfg.
TGF-β Signaling Contributes to Myelofibrosis and Clonal Dominance of Myeloproliferative Neoplasms (W308, Level 3 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_3278;
To test the first hypothesis, we abrogated TGF-β signaling in mesenchymal stem/progenitor cells by deleting Tgfbr2 using a doxycycline-repressible Osterix-Cre transgene (Osx-Cre), which targets all mesenchymal stromal cells in the bone marrow...Conversely, treatment of wildtype MSC cultures with the JNK inhibitor SP600125 abrogated TGF-β1-induced expression of Col1a1...Complete blood counts and donor chimerism were measured 6, 10, 14 and 18 weeks after tamoxifen...In contrast, in the Tgfbr2-deleted group, no expansion of Jak2 mutated cells was observed. These data support our hypothesis that Jak2 mutated HSCs are resistant to the growth suppressive effect of TGF-β, providing a selective advantage that contributes to their clonal expansion in MPN and possibly clonal hematopoiesis.
- |||||||||| doxycycline / Generic mfg.
Gck Kinase Activity Is Critical for RAS Mutated Myeloma - a Potential Treatment Approach for Targeting Specific Mutations (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_2657;
Taken together, our findings provide a rationale for the clinical evaluation of targeting GCK in MM patients and the role of GCK in MM tumorigenesis as well as drug resistance. The subsequent development of small molecules inhibiting this pathway, such as GCK kinase inhibitors, will address the unmet need of developing targeted treatments for RASmut myeloma and potentially for other RASmut malignancies.
- |||||||||| dexamethasone / Generic mfg., doxycycline / Generic mfg.
MAPK-ERK Pathway Activation: The Achilles’ Heel of IL-7R‒Induced Steroid Resistance (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_2112;
We generated doxycycline-inducible SUP-T1 and P12 Ichikawa cell line models that can overexpress specific IL-7R signaling mutants...Exposure to each of three MEK-inhibitors CI1040, Selumetinib or Trametinib abolished not only phospho-ERK but also phosphorylation of BIM...Refractory/relapse T-ALL patients are now eligible for the current phase 1/2 MEK-inhibitor‒dexamethasone (SeluDex) trial. We are using mass-spectrometry to determine the exact phospho-sites in BIM that drives steroid resistance that can serve as a valuable biomarker.
- |||||||||| doxycycline / Generic mfg.
Isoform Specific Regulation of Acute Myeloid Leukemia Maintenance By Wilms Tumor 1 (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_2049;
To further understand how WT1 maintains leukemia, we cloned each of the 8 isoforms into a doxycycline-inducible vector and transduced them into a t(8;21) AML cell line, Kasumi-1, which well recapitulates primary t(8;21) AML (Ptasinska et al., Leukemia, 2014)...Several vaccine studies and more recently a T cell receptor study targeted against WT1 have been undertaken but they have shown mixed efficacy in AML (Chapuis et al, Nature Medicine, 2019). Since we find that different isoforms of WT1 have antagonistic effects, we hypothesise that a more effective therapeutic strategy would be to selectively target only WT1 +KTS isoforms.
- |||||||||| fluorouracil / Generic mfg., doxycycline / Generic mfg.
Canonical Signaling By TGF Family Members in Mesenchymal Stromal Cells Is Dispensable for Hematopoietic Niche Maintenance Under Basal and Stress Conditions (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_2024;
We first performed lineage-tracing studies using Osx-Cre Smad4fl/fl Ai9 mice to show that activation of Osx-Cre at birth (by removal of doxycycline) results in the efficient targeting of bone marrow mesenchymal stromal cells...Moreover, mouse survival after repeated weekly doses of 5-FU was comparable to control mice...HSPC mobilization, as quantified by CFU-C and Kit+ Sca+ lineage- (KSL) cell number in blood or spleen after 5 days of G-CSF treatment was comparable to control mice. Collectively, these data suggest the TGF family member signaling in mesenchymal stromal cells is dispensable for hematopoietic niche maintenance under basal and stress conditions.
- |||||||||| doxycycline / Generic mfg.
Inducible Expression of Mutant ELANE Correlates with Disruption of Differentiation Program, but Not the Unfolded Protein Response (Tangerine 3 (WF3-4), Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_1407;
However multiple studies of UPR activation reported a requirement of treatment with chemical UPR inducers such as tunicamycin or bortezomib to observe significant changes...Methods.We created a doxycycline inducible expression system of ELANE, consisting of wild type (wt) and point mutation (G185R) variant associated with SCN, in the murine myeloblast cell line 32D and the human promyelocytic leukemia cell line NB4...We also show a concomitant upregulation of cell proliferation genes upon mutant ELANE expression. This detour from a differentiation profile may indicate pre-leukemic underpinnings for G-CSF treatment in SCN.
- |||||||||| doxycycline / Generic Mfg.
Journal: A piggyBac-based toolkit for inducible genome editing in mammalian cells. (Pubmed Central) - Nov 6, 2019
In CRISPR-Bac, a single piggyBac cargo vector containing a doxycycline-inducible Cas9 or catalytically dead Cas9 (dCas9) variant and a gene conferring resistance to Hygromycin B is cotransfected with a plasmid expressing the piggyBac transposase...sgRNAs targeting multiple genes can be inserted in a single transfection. CRISPR-Bac is a versatile platform for genome editing that simplifies the generation of mammalian cells that stably express the CRISPR-Cas9 machinery.
- |||||||||| doxycycline / Generic Mfg.
Journal, CAR T-Cell Therapy, IO Biomarker: Doxycycline Inducible Chimeric Antigen Receptor T Cells Targeting CD147 for Hepatocellular Carcinoma Therapy. (Pubmed Central) - Nov 5, 2019
Taken together, our results indicated that the expression and activity of CD147CAR were controlled by Dox both in vitro and in vivo, which facilitated decreased toxicity and adverse effects to CAR-T cell therapy. Moreover, this study provides viable evidence in support of the potential benefits and translation of this strategy of CAR-T cells targeting CD147 for the treatment of patients with HCC.
- |||||||||| doxycycline / Generic Mfg.
ERG promotes the methylation reprogramming in prostate cancer onset () - Nov 5, 2019 - Abstract #NCRI2019NCRI_305;
This early gain of function aligns with what we firstly confirmed, in fact, ERG overexpression assesses an initial EMT phenotype switch, promoting the upregulation of mesenchymal markers and factors such as vimentin, CDH2, and ZEB1, while on the other hand a slight reduction of CDH1 and Slug expression. Interestingly, our analyses showed that ERG upregulation also affects DNA methyltransferases expression.
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