- |||||||||| doxycycline / Generic Mfg.
A potent synergy between FOXG1 overexpression and Wnt signaling drives cell cycle re-entry in quiescent glioblastoma stem cells (Hall 4) - Nov 5, 2019 - Abstract #NCRI2019NCRI_130;
Method We use an in vitro model of quiescence in mouse neural stem cells, incorporating a doxycycline inducible human FOXG1 overexpression cassette, to identify, through high content pharmacological screening, a synergistic relationship between high FOXG1 expression and inhibition of glycogen synthase kinase 3 (GSK3) in driving cells into an active, proliferative state... Finally, we have developed a mouse model of glioblastoma by excision of NF-1 and Pten and overexpression of EGFRvIII in cells with inducible active beta-catenin and FOXG1. Conclusion Targeting the synergistic relationship between FOXG1 and beta-catenin may provide an exciting therapeutic opportunity in preventing relapse and improving the prognosis of glioblastoma.
- |||||||||| cephalexin / Generic mfg., trimethoprim/sulfamethoxazole / Generic mfg., doxycycline / Generic mfg.
Trial completion date, Trial primary completion date: Effects of Treatments on Atopic Dermatitis (clinicaltrials.gov) - Nov 4, 2019
P2, N=130, Recruiting,
Conclusion Targeting the synergistic relationship between FOXG1 and beta-catenin may provide an exciting therapeutic opportunity in preventing relapse and improving the prognosis of glioblastoma. Trial completion date: Jun 2020 --> Dec 2022 | Trial primary completion date: Jun 2020 --> Jan 2022
- |||||||||| doxycycline / Generic Mfg.
Preclinical, Journal: Plasma and brain concentrations of doxycycline after single and repeated doses in wild-type and APP23 mice. (Pubmed Central) - Nov 2, 2019
Notably, these concentrations are lower than those required for the drug's anti-aggregating properties as observed in cell-free studies, suggesting that other features underlie the positive cognitive effects in AD mice; iv) elimination half-life was shorter than in humans (3-6h vs 15-30h), therefore no significant accumulation was observed in mouse brain following repeated treatments; v) there were no differences between doxycycline concentrations in brain areas of age-matched wild-type and APP23 mice. These data are useful for planning preclinical studies with translational validity, and to identify the mechanism(s) of action underlying the central in vivo effects of doxycycline more reliably.
- |||||||||| Trial completion, Enrollment change, Trial completion date, Trial primary completion date: APRiCCOT: Antibiotics and Hydroxychloroquine in Crohn's (clinicaltrials.gov) - Nov 1, 2019
P2, N=59, Completed,
These data are useful for planning preclinical studies with translational validity, and to identify the mechanism(s) of action underlying the central in vivo effects of doxycycline more reliably. Recruiting --> Completed | N=100 --> 59 | Trial completion date: Dec 2019 --> Sep 2019 | Trial primary completion date: Dec 2019 --> Apr 2019
- |||||||||| doxycycline / Generic Mfg., Garamycin (gentamicin sulfate) / Generic Mfg.
Journal: Serendipitous Treatment of Tularemia in Pregnancy. (Pubmed Central) - Oct 30, 2019
A Centers for Disease Control and Prevention report on the macrolide susceptibility of North American isolates of this organism has been underappreciated. The unanticipated result from this patient may give another potential option for treatment of tularemia in pregnancy.
- |||||||||| doxycycline / Generic Mfg.
Journal: Mupirocin resistance among Methicillin resistant Staphylococcus isolates in a tertiary health care center. (Pubmed Central) - Oct 29, 2019
The unanticipated result from this patient may give another potential option for treatment of tularemia in pregnancy. It was concluded that an inappropriate excessive use of mupirocin leads to a rapid increase in high-level resistance to mupirocin and other antibiotics in CoNS, affecting the treatment lines and success rate of infection control in hospital settings.
- |||||||||| doxycycline / Generic Mfg.
Retrospective data, Review, Journal: Non-standard treatment for uncomplicated Chlamydia trachomatis urogenital infections: a systematic review. (Pubmed Central) - Oct 29, 2019
It was concluded that an inappropriate excessive use of mupirocin leads to a rapid increase in high-level resistance to mupirocin and other antibiotics in CoNS, affecting the treatment lines and success rate of infection control in hospital settings. The paucity of existing data highlights the need for further adequately powered studies to evaluate rifalazil, delayed release doxycycline, levofloxacin and other agents for the treatment of uncomplicated CT infections.
- |||||||||| doxycycline / Generic Mfg.
Biomarker, Journal: Loss of KDM6A characterizes a poor prognostic subtype of human pancreatic cancer and potentiates HDAC inhibitor lethality. (Pubmed Central) - Oct 29, 2019
We established KDM6A knocked out cells by using the CRISPR/Cas9 system and KDM6A-expressed cells by doxycycline-inducible system from each two human PDAC cell lines, respectively...Consistent with these results, the KDM6A knockout cells demonstrated higher vulnerability to histone deacetylase (HDAC) inhibitors through the reactivation of CDKN1A in vitro and in vivo than the KDM6A wild-type. In conclusion, KDM6A exhibited essential roles in human PDAC as a tumor suppressor and KDM6A deficiency could be a promising biomarker for unfavorable outcome in PDAC patients and a potential surrogate marker for response to HDAC inhibitors.
- |||||||||| doxycycline / Generic Mfg.
A mouse model of FGFR3-TACC3 uncovers mechanisms of gliomagenesis and maintenance (Grand Canyon 1-6) - Oct 29, 2019 - Abstract #SNO2019SNO_1413;
We generated a knock-in mouse in which the expression of FGFR3-TACC3 is doxycycline inducible and reversible...Our findings validate FGFR3-TACC3 as powerful oncogene that drives development of high-grade glioma from distinct areas of the brain. They also provide an accurate pre-clinical model in which glioma maintenance requires continuous expression of the fusion gene, thus supporting therapeutic targeting of the fusion protein in patients with FGFR3-TACC3-positive glioblastoma.
- |||||||||| doxycycline / Generic Mfg.
Investigating the effect of H3G34V mutation on distinct genomic H3K36 methylation patterns in pediatric glioma (Ballroom Lawn) - Oct 29, 2019 - Abstract #SNO2019SNO_1216;
Methods Doxycycline-inducible short hairpin RNA (shRNA) against H3F3Awas delivered via lentivirus to established H3G34V mutant pediatric glioma cell line KNS42, and H3G34V introduced into H3.3 wild type normal human astrocytes (NHA)...Conclusions We demonstrate that DOX-inducible knockdown of H3F3Ain an H3G34V mutant pediatric glioma cell line, and H3G34V mutation transduction in wild-type NHAs, directly impacts H3K36me3 expression level. Further evaluation by ChIP-Seq analysis for restoration of wild-type genomic H3K36me3 enrichment patterns with H3G34V knockdown, and mutant H3K36me3 patterns with H3G34V transduction, is currently underway.
- |||||||||| Avastin (bevacizumab) / Roche, doxycycline / Generic Mfg.
Targeting metabolic pathways in hypoxia for Glioblastoma (Ballroom Lawn) - Oct 29, 2019 - Abstract #SNO2019SNO_987;
Peroxisomal FAO and other metabolic pathways may be essential to target in order combat metabolic resistance during anti-angiogenic therapy. Better understanding differences in metabolism in different tumor environments will help determine which targets will be most therapeutically useful.
- |||||||||| doxycycline / Generic Mfg.
Journal, PD(L)-1 Biomarker, IO Biomarker: Inducible IFN-γ Expression for MHC-I Upregulation in Devil Facial Tumor Cells. (Pubmed Central) - Oct 28, 2019
IFN-γ can have negative effects on cell proliferation and viability; thus, doxycycline was used to suppress IFN-γ production whilst DFT1.Tet/IFN-γ cells were expanded in cell culture...This system represents a major step forward in DFT disease immunotherapy and vaccine development efforts, and ability to understand gene function in devils. Importantly, the techniques are readily transferable for testing gene function in DFT2 cells and other non-traditional species.
- |||||||||| doxycycline / Generic Mfg.
Clinical, Journal: Isolation and identification of R. raoultii in human cases: a surveillance study in three medical centers in China. (Pubmed Central) - Oct 27, 2019
All the 19 patients recovered without sequelae after receiving doxycycline treatment...Human infection with R. raoultii has a wide clinical spectrum that ranged from subclinical infection to severe complications. Physicians need to be aware of the high potential and clinical complexity of R. raoultii infection, to ensure appropriate testing and treatment in endemic regions.
- |||||||||| doxycycline / Generic Mfg.
Preclinical, Journal: Assessment of the direct effects of DDAH I on tumour angiogenesis in vivo. (Pubmed Central) - Oct 27, 2019
A clone of rat C6 glioma cells deficient in NO production expressing a pTet Off regulatable element was identified and engineered to overexpress DDAH I in the absence of doxycycline...However, overexpression of DDAH I had no measurable effect on tumour growth, vessel density, function or maturation. These data suggest that in C6 gliomas DDAH has no NO-independent effects on tumour growth and angiogenesis, and that the therapeutic potential of targeting DDAH in gliomas should only be considered in the context of NO regulation.
- |||||||||| doxycycline / Generic mfg.
Ex vivo Engineering of Platelets (Hall E2, Level 2 (Orange County Convention Center)) - Oct 27, 2019 - Abstract #ASH2019ASH_621;
For the former, our key measure is to expand the immortalized megakaryocyte cell lines (imMKCLs) derived from iPSCs, whereby c-MYC, BMI-1, and Bcl-XL are overexpressed under doxycycline-inducible system to regulate proliferation of megakaryocyte progenitors (Cell Stem Cell, 2014)...Therefore, we evaluated the immunological reaction between HLA-null platelets and NK cells by using our newly developed alloimmune PTR in vivo model in which human NK cells are highly reconstituted in MISTRG mice (Suzuki and Sugimoto et al.,manuscript in revision). This pre-clinical study model should provide a proof-of concept for the clinical application of HLA-null iPS-platelets as a universal platelet product for future transfusion.
- |||||||||| doxycycline / Generic mfg.
Ex vivo Engineering of Platelets (Tangerine 2 (WF2), Level 2 (Orange County Convention Center)) - Oct 27, 2019 - Abstract #ASH2019ASH_618;
For the former, our key measure is to expand the immortalized megakaryocyte cell lines (imMKCLs) derived from iPSCs, whereby c-MYC, BMI-1, and Bcl-XL are overexpressed under doxycycline-inducible system to regulate proliferation of megakaryocyte progenitors (Cell Stem Cell, 2014)...Therefore, we evaluated the immunological reaction between HLA-null platelets and NK cells by using our newly developed alloimmune PTR in vivo model in which human NK cells are highly reconstituted in MISTRG mice (Suzuki and Sugimoto et al.,manuscript in revision). This pre-clinical study model should provide a proof-of concept for the clinical application of HLA-null iPS-platelets as a universal platelet product for future transfusion.
- |||||||||| doxycycline / Generic Mfg.
Journal: Indurated Plaque with Bullae Formation on the Left Arm. (Pubmed Central) - Oct 27, 2019
Before presentation, he had undergone treatment with cephalexin, prednisone, and doxycycline without reported improvement. Laboratory studies were negative for antinuclear antibody and SCL70 antibody; however, an absolute eosinophilia of 1478/uL was noted.
- |||||||||| doxycycline / Generic Mfg.
Journal: Doxycycline release and antibacterial activity from PMMA/PEO electrospun fiber mats. (Pubmed Central) - Oct 27, 2019
Laboratory studies were negative for antinuclear antibody and SCL70 antibody; however, an absolute eosinophilia of 1478/uL was noted. The incorporation of PEO at 20% and 30% into PMMA fiber mat resulted in effective drug release systems, with detected antibacterial activity against S. mutans.
- |||||||||| doxycycline / Generic Mfg.
Journal: Microbiological Profile of Infections in a Tertiary Care Burns Unit. (Pubmed Central) - Oct 26, 2019
Gram-positive isolates had better susceptibility to macrolides, doxycycline, glycopeptides...Ebenezer R, Princess I, Vadala R, Kumar S, Ramakrishnan N, Krishnan G. Microbiological Profile of Infections in a Tertiary Care Burns Unit. Indian J Crit Care Med 2019;23(9):405-410.
- |||||||||| doxycycline / Generic Mfg.
Retrospective data, Review, Journal: Urogenital chlamydia trachomatis treatment failure with azithromycin: A meta-analysis. (Pubmed Central) - Oct 26, 2019
The meta-regression results showed that the patient's age contributes significantly to the heterogeneity for azithromycin treatment failure rate (β░=░0.826; p░=░0.017). Azithromycin has a higher failure rate than doxycycline and other studied medications in treating urogenital chlamydia infections.
- |||||||||| doxycycline / Generic Mfg.
Journal: JDP2 overexpression provokes cardiac dysfunction in mice. (Pubmed Central) - Oct 25, 2019
Therefore, during birth up to the age of 4 weeks cardiac-specific JDP2 overexpression was prevented by doxycycline feeding in transgenic mice...It can be concluded that JDP2 overexpression provokes cardiac dysfunction in adult mice that is accompanied by hypertrophy and fibrosis. Thus, induction of JDP2 is a maladaptive response contributing to heart failure development.
- |||||||||| doxycycline / Generic Mfg.
Preclinical, Journal: Antibacterial effects of polymeric PolymP-n Active nanoparticles. An in vitro biofilm study. (Pubmed Central) - Oct 24, 2019
The haemolymph activity of both studied parameters increased together with study time and tetracycline administration time. Polymeric PolymP-n Active nanoparticles when combined with silver and doxycycline showed a significant antibacterial effect when tested in an in vitro subgingival biofilm model.
- |||||||||| Pulmonary Necrotic Rhodococcus equi Infection in a Kidney Pancreas Transplant Recipient: A Rare Case Treated Without Surgical Intervention () - Oct 23, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_5880;
He had been prescribed azithromycin, doxycycline, and ciprofloxacin by his local providers with no improvement...He was started on IV vancomycin, meropenem for 6 weeks and his symptoms improved...He was also given voriconazole for his aspergilllus for 12 months.Repeat chest imaging near total improvement in the cavitary lesion and his symptoms resolved over the next 6-9 months...Here we report a very rare case of Rhodococcus infection in a kidney pancreas transplant recipient which was successfully treated without surgical intervention. Choice of antibiotics were challenging while maintaining dual organ transplant function and avoiding acute rejection.
- |||||||||| doxycycline / Generic mfg.
Trial completion date: Doxycycline for COPD in HIV-Infected Patients (clinicaltrials.gov) - Oct 22, 2019
P=N/A, N=61, Active, not recruiting,
The study sheds new light on suitable additives to analyse basic compounds with the advantage of good compatibility with MS detection. Trial completion date: Dec 2019 --> Dec 2020
- |||||||||| Actemra IV (tocilizumab) / Roche, JW Pharma, Valcyte (valganciclovir) / Roche, Mitsubishi Tanabe, Kineret (anakinra) / SOBI
Trial completion date, Trial primary completion date: Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants (clinicaltrials.gov) - Oct 22, 2019
P=N/A, N=500, Recruiting,
Trial completion date: Dec 2019 --> Dec 2020 Trial completion date: Sep 2019 --> Sep 2020 | Trial primary completion date: Sep 2019 --> Sep 2020
- |||||||||| doxycycline / Generic Mfg.
Journal: A single point mutation in the rhinovirus 2B protein reduces the requirement for phosphatidylinositol 4-kinase class 3beta in viral replication. (Pubmed Central) - Oct 20, 2019
Doxycycline-inducible expression of PI4K3b in PI4K3b knockout cells efficiently rescued the 2B[I92T] mutant and, less effectively, wild-type virus infection...The identification of critical host factors and their interactions with viral proteins and membrane lipids for the establishment of viral replication is a basis for drug development strategies. Our findings here shed new light on the interactions between nonstructural viral membrane proteins and class III phosphatidylinositol 4 kinases from the host, and highlight the importance of phosphatidyl-inositol 4 phosphate for RV replication.
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