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Anti-cancer Agents in Medicinal... 2017Cancer cells do create hostile microenvironment (deprivation of nutrients, accumulation of acidity, anoxic habitat). Those cells are not only adapted to this sanctuary... (Review)
Review
Cancer cells do create hostile microenvironment (deprivation of nutrients, accumulation of acidity, anoxic habitat). Those cells are not only adapted to this sanctuary environment, blunting of immunity but also, grow, migrate to the distal area (metastasis) and communicate with each other in a unique population structure and organization too (clonal expansion). The adaptation requirements push those types of adaptable cells (cancer cells) to be primitive cells. The prevailing pharmacological approach in treating cancer is developing a chemotherapeutic agent that acts on rapidly proliferating cells that are stuck with normally growing epithelium and bone marrow too. The latter approach has been drafted to work on cellular target under the term of "targeted therapy" believing that each target represents Achilles Heels of cancer. In this article, we try to introduce a new concept of cancer pharmacology, by offering new off-label use of Doxycycline, which is characterized by selective toxicity, as potential anticancer agents. This notion is relying on the absence of taxonomic barriers.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Doxycycline; Humans; Neoplasm Metastasis; Neoplasms; Quorum Sensing; Tumor Microenvironment
PubMed: 28270076
DOI: 10.2174/1871520617666170213111951 -
Journal of Neural Transmission (Vienna,... Jun 2022The novel antibiotic-exploiting strategy in the treatment of Alzheimer's (AD) and Parkinson's (PD) disease has emerged as a potential breakthrough in the field. The... (Review)
Review
The novel antibiotic-exploiting strategy in the treatment of Alzheimer's (AD) and Parkinson's (PD) disease has emerged as a potential breakthrough in the field. The research in animal AD/PD models provided evidence on the antiamyloidogenic, anti-inflammatory, antioxidant and antiapoptotic activity of tetracyclines, associated with cognitive improvement. The neuroprotective effects of minocycline and doxycycline in animals initiated investigation of their clinical efficacy in AD and PD patients which led to inconclusive results and additionally to insufficient safety data on a long-standing doxycycline and minocycline therapy in these patient populations. The safety issues should be considered in two levels; in AD/PD patients (particularly antibiotic-induced alteration of gut microbiota and its consequences), and as a world-wide threat of development of bacterial resistance to these antibiotics posed by a fact that AD and PD are widespread incurable diseases which require daily administered long-lasting antibiotic therapy. Recently proposed subantimicrobial doxycycline doses should be thoroughly explored for their effectiveness and long-term safety especially in AD/PD populations. Keeping in mind the antibacterial activity-related far-reaching undesirable effects both for the patients and globally, further work on repurposing these drugs for a long-standing therapy of AD/PD should consider the chemically modified tetracycline compounds tailored to lack antimicrobial but retain (or introduce) other activities effective against the AD/PD pathology. This strategy might reduce the risk of long-term therapy-related adverse effects (particularly gut-related ones) and development of bacterial resistance toward the tetracycline antibiotic agents but the therapeutic potential and desirable safety profile of such compounds in AD/PD patients need to be confirmed.
Topics: Alzheimer Disease; Animals; Anti-Bacterial Agents; Doxycycline; Drug Repositioning; Humans; Minocycline; Parkinson Disease; Tetracycline
PubMed: 34982206
DOI: 10.1007/s00702-021-02457-2 -
Journal of Inherited Metabolic Disease Jul 2022
Topics: Doxycycline; Humans; Mitochondria; Mitochondrial Diseases
PubMed: 35734980
DOI: 10.1002/jimd.12531 -
Clinical Infectious Diseases : An... May 2020Scrub typhus, a neglected infectious disease caused by the obligate intracellular bacterium Orientia tsutsugamushi, is a major cause of fever across the Asia Pacific... (Review)
Review
Scrub typhus, a neglected infectious disease caused by the obligate intracellular bacterium Orientia tsutsugamushi, is a major cause of fever across the Asia Pacific region with more than a billion people at risk. Treatment with antibiotics such as doxycycline or chloramphenicol is effective for the majority of patients. In the 1990s, reports from northern Thailand raised a troubling observation; some scrub typhus patients responded poorly to doxycycline, which investigators attributed to doxycycline resistance. Despite the controversial nature of these reports, independent verification was neglected, with subsequent studies speculating on the role of doxycycline resistance in contributing to failure of treatment or prophylaxis. In this review, we have outlined the evidence for drug-resistant Orientia tsutsugamushi, assessed the evidence for doxycycline resistance, and highlight more recent findings unsupportive of doxycycline resistance. We conclude that doxycycline resistance is a misconception, with treatment outcome likely to be determined by other bacterial, host, and pharmacological factors.
Topics: Anti-Bacterial Agents; Doxycycline; Humans; Orientia tsutsugamushi; Scrub Typhus; Thailand
PubMed: 31570937
DOI: 10.1093/cid/ciz972 -
Microbial Pathogenesis Oct 2023Brucellosis is a zoonotic disease that can be transmitted from animals to humans. Brucellosis is caused by bacteria of the genus Brucella, which are typically... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Brucellosis is a zoonotic disease that can be transmitted from animals to humans. Brucellosis is caused by bacteria of the genus Brucella, which are typically transmitted through contact with infected animals, unpasteurized dairy products, or airborne pathogens. Tetracyclines (tetracycline and doxycycline) are antibiotics commonly used to treat brucellosis; however, antibiotic resistance has become a major concern. This study assessed the worldwide prevalence of tetracycline-resistant Brucella isolates.
METHODS
A systematic search was conducted in Scopus, PubMed, Web of Science, and EMBASE using relevant keywords and Medical Subject Headings (MeSH) terms until August 13, 2022, to identify relevant studies for meta-analysis. A random effects model was used to estimate the proportion of resistance. Meta-regression analysis, subgroup analysis, and examination of outliers and influential studies were also performed.
RESULTS
The prevalence rates of resistance to tetracycline and doxycycline were estimated to be 0.017 (95% confidence interval [CI], 0.009-0.035) and 0.017 (95%CI, 0.011-0.026), respectively, based on 51 studies conducted from 1983 to 2020. Both drugs showed increasing resistance over time (tetracycline: r = 0.077, P = 0.012; doxycycline: r = 0.059, P = 0.026).
CONCLUSION
The prevalence of tetracycline and doxycycline resistance in Brucella was low (1.7%) but increased over time. This increase in tetracycline and doxycycline resistance highlights the need for further research to understand resistance mechanisms and develop more effective treatments.
Topics: Animals; Humans; Brucella melitensis; Brucella abortus; Tetracycline; Doxycycline; Prevalence; Brucellosis; Anti-Bacterial Agents; Tetracyclines
PubMed: 37673354
DOI: 10.1016/j.micpath.2023.106321 -
Dental Materials : Official Publication... Jun 2023To evaluate the effect of doxycycline and dexamethasone doped nanoparticles covering titanium surfaces, on osteoblasts proliferation and differentiation.
OBJECTIVES
To evaluate the effect of doxycycline and dexamethasone doped nanoparticles covering titanium surfaces, on osteoblasts proliferation and differentiation.
METHODS
Doxycycline and dexamethasone doped polymeric nanoparticles were applied on titanium discs (Ti-DoxNPs and Ti-DexNPs). Undoped NPs and uncovered Ti discs were used as control. Human MG-63 osteoblast-like cells were cultured. Osteoblasts proliferation was tested by MTT assay. Alkaline phosphatase activity was analyzed. Differentiation gene expression was assessed by real-time quantitative polymerase chain reaction. Scanning Electron Microscopy was performed to assess osteoblasts morphology. Mean comparisons were conducted by ANOVA and Wilcoxon or Tukey tests (p < 0.05).
RESULTS
No differences in osteoblasts proliferation were found. Osteoblasts grown on Ti-DoxNPs significantly increased alkaline phosphatase activity. Doxycycline and dexamethasone nanoparticles produced an over-expression of the main osteogenic proliferative genes (TGF-β1, TGF-βR1 and TGF-βR2). The expression of Runx-2 was up-regulated. The osteogenic proteins (AP, OSX and OPG) were also overexpressed on osteoblasts cultured on Ti-DoxNPs and Ti-DexNPs. The OPG/RANKL ratio was the highest when DoxNPs were present (75-fold increase with respect to the control group). DexNPs also produced a significantly higher OPG/RANKL ratio with respect to the control (20 times higher). Osteoblasts grown on titanium discs were mainly flat and polygonal in shape, with inter-cellular connections. In contrast, osteoblasts cultured on Ti-DoxNPs or Ti-DexNPs were found to be spindle-shaped and had abundant secretions on their surfaces.
SIGNIFICANCE
DoxNPs and DexNPs were able to stimulate osteoblasts differentiation when applied on titanium surfaces, being considered potential inducers of osteogenic environment when performing regenerative procedures around titanium dental implants.
Topics: Humans; Titanium; Doxycycline; Alkaline Phosphatase; Cell Differentiation; Osteogenesis; Nanoparticles; Dexamethasone; Osteoblasts; Surface Properties; Cell Proliferation
PubMed: 37173196
DOI: 10.1016/j.dental.2023.05.004 -
American Journal of Health-system... Mar 2016A probable case of doxycycline-induced pancreatitis is reported.
PURPOSE
A probable case of doxycycline-induced pancreatitis is reported.
SUMMARY
A 51-year-old man was admitted to the emergency department with a one-week history of extreme fatigue, malaise, and confusion. Three days earlier he had been started on empirical doxycycline therapy for presumed Lyme disease; he was taking no other medications at the time of admission. A physical examination was remarkable for abdominal tenderness. Relevant laboratory data included a lipase concentration of 5410 units/L (normal range, 13-60 units/L), an amylase concentration of 1304 (normal range, 28-100 units/L), and a glycosylated hemoglobin concentration of 15.2% (normal, <5.7%). Tests for immunoglobulin G4, Lyme disease antibodies, influenza strains, human immunodeficiency virus, and hepatitis A, B, and C were all negative. Blood, urine, cerebrospinal fluid, and respiratory cultures showed no growth. Abdominal computed tomography findings were consistent with acute pancreatitis (AP). The patient was admitted to the intensive care unit and intubated, and doxycycline was discontinued. With vasopressor support, aggressive fluid resuscitation, hemodialysis, and an insulin infusion, the patient's clinical course rapidly improved over five days. Scoring of the case via the method of Naranjo et al. yielded a score of 6, indicating a probable adverse reaction to doxycycline.
CONCLUSION
A man developed AP three days after starting therapy with oral doxycycline, and the association between drug and reaction was determined to be probable. His case appears to be the third of doxycycline-associated AP, although tigecycline, tetracycline, and minocycline have also been implicated as causes of AP.
Topics: Anti-Bacterial Agents; Doxycycline; Humans; Male; Middle Aged; Pancreatitis
PubMed: 26896500
DOI: 10.2146/ajhp150298 -
Deutsches Arzteblatt International Mar 2020
Topics: Antimalarials; Dermatitis, Phototoxic; Doxycycline; Female; Humans; Young Adult
PubMed: 32343652
DOI: 10.3238/arztebl.2020.0196 -
Current Opinion in Pharmacology Feb 2019Prion-related encephalopathies or transmissible spongiform encephalopathies (TSEs) are a group of rare progressive neurodegenerative disorders that are invariably fatal... (Review)
Review
Prion-related encephalopathies or transmissible spongiform encephalopathies (TSEs) are a group of rare progressive neurodegenerative disorders that are invariably fatal with often only six months elapsing from diagnosis to patient death. This makes the development of effective therapeutic strategies challenging. Nonetheless, compounds have been identified in animal models of TSE that prolong survival and, in some instances, eradicate the disease. These have been tested in the clinic, although with modest or negative outcomes. While little progress has been made over the last decade, new findings that include the ability to identify prion aggregates at low levels in biological fluids and cells may lead to the development of early-stage biomarkers for TSE. An increased focus on immunotherapeutic approaches to TSE may result in the development of novel preventive approaches for TSE.
Topics: Animals; Doxycycline; Humans; Immunotherapy; Prion Diseases
PubMed: 31108459
DOI: 10.1016/j.coph.2019.04.019 -
Travel Medicine and Infectious Disease 2022Antibiotics predispose travellers to acquire multidrug-resistant bacteria, such as extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). Although widely... (Review)
Review
BACKGROUND
Antibiotics predispose travellers to acquire multidrug-resistant bacteria, such as extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). Although widely used in antimalarial prophylaxis, doxycycline has scarcely been studied in this respect.
METHODS
We explored the impact of doxycycline on rates of traveller's diarrhoea (TD), ESBL-PE acquisition and, particularly, doxycycline co-resistance among travel-acquired ESBL-PE in a sample of 412 visitors to low- and middle-income countries. We reviewed the literature on traveller studies of doxycycline/tetracycline resistance among stool pathogens and the impact of doxycycline on TD rates, ESBL-PE acquisition, and doxycycline/tetracycline resistance.
RESULTS
The TD rates were similar for doxycycline users (32/46; 69.6%) and non-users (256/366; 69.9%). Of the 90 travel-acquired ESBL-PE isolates, 84.4% were co-resistant to doxycycline: 100% (11/11) among users and 82.3% (65/79) among non-users. The literature on doxycycline's effect on TD was not conclusive nor did it support a recent decline in doxycycline resistance. Although doxycycline did not increase ESBL-PE acquisition, doxycycline-resistance among stool pathogens proved more frequent for users than non-users.
CONCLUSIONS
Our prospective data and the literature review together suggest the following: 1) doxycycline does not prevent TD; 2) doxycycline use favours acquisition of doxy/tetracycline-co-resistant intestinal bacteria; 3) although doxycycline does not predispose to travel-related ESBL-PE acquisition per se, it selects ESBL-PE strains co-resistant to doxycycline; 4) doxycycline resistance rates are high among stool bacteria in general with no evidence of any tendency to decrease.
Topics: Anti-Bacterial Agents; Antimalarials; Bacteria; Diarrhea; Doxycycline; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Prospective Studies; Travel; Travel-Related Illness; beta-Lactamases
PubMed: 35872253
DOI: 10.1016/j.tmaid.2022.102403