Tumour relapse, chemotherapy resistance, and metastasis continue to be unsolved issues in cancer therapy. A recent approach has been to scrutinise drugs used in the clinic for other illnesses and modify their structure to increase selectivity to cancer cells. Chloroquine (CQ) and hydroxychloroquine (HCQ), known antimalarials, have successfully treated autoimmune and neoplastic diseases. CQ and HCQ, well-known lysosomotropic agents, induce apoptosis, downregulate autophagy, and modify the tumour microenvironment. Moreover, they affect the Toll 9/NF-κB receptor pathway, activate stress response pathways, enhance p53 activity and CXCR4-CXCL12 expression in cancer cells, which would help explain their effects in cancer treatment. These compounds can normalise the tumourassociated vasculature, promote the activation of the immune system, change the phenotype of tumour-associated macrophages (from M2 to M1), and stimulate cancer-associated fibroblasts. We aim to review the historical aspects of CQ and its derivatives and the most relevant mechanisms that support the therapeutic use of CQ and HCQ for the treatment of cancer.
- MeSH
- antimalarika * farmakologie terapeutické užití MeSH
- chlorochin farmakologie terapeutické užití MeSH
- hydroxychlorochin * farmakologie terapeutické užití MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- nádorové mikroprostředí MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Systémový lupus erythematodes (SLE) je autoimunitní onemocnění s rozmanitými projevy, jehož diagnostika může být nesnadná. Léčba vyžaduje multioborový přístup a pravidelný screening orgánových manifestací. V terapii SLE se uplatňují nefarmakologické postupy (fotoprotekce, nekouření, dostatek pohybu, zdravá strava), pilířem pak je farmakologická léčba, jejíž výběr se řídí charakteristikami pacienta, typem a závažností orgánového postižení, komorbiditami i preferencemi pacienta. Klíčovými farmaky jsou hydroxychlorochin, kortikosteroidy (při vzplanutí onemocnění a těžkém orgánovém postižení) a imunosupresiva (metotrexát, azathioprin, mykofenolát mofetil), z biologických léků pak je možné použít belimumab či anifrolumab. U pacientů se závažným orgánovým postižením či život ohrožujícím stavem jsou léky volby cyklofosfamid či rituximab.
Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous symptoms, whose diagnostics may not be easy. Treatment of SLE requires a multidisciplinary approach and a regular screening of organ manifestations. Therapy of SLE comprises nonpharmacological measures (photoprotection, nonsmoking, physical activity, healthy diet), the mainstay is pharmacological treatment, which is chosen according to the patient ́s characteristics, type and severity of organ damage, comorbidities as well as patient ́s preferences. The most important drugs are hydroxychloroquine, corticosteroids (in case of disease flare and severe organ damage) and immunosuppressants (methotrexate, azathioprine, mycophenolate mofetil), from the class of biological drugs, it is possible to use belimumab or anifrolumab. In patients with serious organ damage or lifethreatening condition, the treatment of choice includes cyclophosphamide or rituximab.
- Klíčová slova
- belimumab,
- MeSH
- glukokortikoidy farmakologie terapeutické užití MeSH
- humanizované monoklonální protilátky farmakologie terapeutické užití MeSH
- hydroxychlorochin farmakologie terapeutické užití MeSH
- imunosupresiva farmakologie terapeutické užití MeSH
- inhibitory kalcineurinu farmakologie terapeutické užití MeSH
- lidé MeSH
- rituximab farmakologie terapeutické užití MeSH
- systémový lupus erythematodes * farmakoterapie klasifikace patologie MeSH
- Check Tag
- lidé MeSH
Cryptococcus neoformans is an opportunistic fungal pathogen that can cause life-threatening invasive fungal infections. As its prevalence and drug resistance continue to rise, cryptococcosis requires new treatment options. Tapping into the potential antifungal effects of traditional drugs or combination therapy has become one of the options. This study was the first to examine the interaction of hydroxychloroquine (HCQ) and itraconazole (ITR) on Cryptococcus neoformans in vitro and in vivo. Our results showed that HCQ alone and in combination with ITR exhibited antifungal activity against C. neoformans planktonic cells. When HCQ was combined with ITR, the minimal inhibitory concentration (MIC) value of HCQ decreased to 32 μg/mL, and the MIC value of ITR decreased from 0.25 μg/mL to 0.06-0.25 μg/mL. The time-killing curve showed that the combined application of HCQ and ITR significantly shortened the killing time, dynamically defining the antifungal activity. The minimum biofilm clearance concentration (MBEC) of HCQ was only 32 μg/mL, which was significantly lower than the MIC of HCQ for planktonic cells. When combined with ITR, the MBEC of ITR decreased from 128 μg/mL to 2-1 μg/mL, and the MBEC of HCQ decreased from 32 μg/mL to 4 μg/mL, indicating a synergistic antifungal biofilm effect. In comparison to ITR alone, the combination of HCQ and ITR treatment increased the survival of C. neoformans-infected Galleria mellonella larvae and decreased the fungal burden of infected larvae. Mechanistic investigations revealed that HCQ might damage C. neoformans cell membranes, impact the structure of fungal cells, cause extracellular material leakage, and have a potent affinity for attaching to the C. neoformans genomic DNA. In conclusion, HCQ has potential clinical application in the treatment of cryptococcosis.
- MeSH
- antifungální látky farmakologie terapeutické užití MeSH
- Cryptococcus neoformans * MeSH
- hydroxychlorochin farmakologie terapeutické užití MeSH
- itrakonazol farmakologie MeSH
- kryptokokóza * farmakoterapie mikrobiologie MeSH
- mikrobiální testy citlivosti MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Introduction: Coronavirus pandemic is currently a global health concern with no established treatment guidelines. The aim of the present study was to determine the therapeutic effectiveness of hydroxychloroquine combined with azithromycin in patients with positive coronavirus disease 2019 (COVID-19) admitted to the hospital with severe dyspnea, as well as the incidence of occurrence of adverse effects.Methods: It was intended to utilize a retrospective clinical study of approximately 250 adult patients admitted to the ALSALAM Teaching Hospital in Mosul city with mild to moderate COVID-19 in order to evaluate treatment efficacy in combination with clinical and biochemical findings. Two groups were involved in the research. The first patient group consisted of 250 people who got hydroxychloroquine in conjunction with azithromycin, while the second untreated control group consisted of 100 individuals who received no medication as part of the research.Results: Baseline parameters (clinical and biochemical assays) did not vary substantially among the two groups. Patients in the treatment group were hospitalized at a rate of 30%, compared to 27% in the untreated control group (P<0.001). Between groups, there were no statistically significant changes in mortality,non-invasive oxygen demand, or hospitalization duration. Biochemical and Clinical outcomes were comparable between those receiving hydroxychloroquine with azithromycin and those do not receive any medication.Conclusion: This treatment regimen was shown to be not affective in mild to severe positve COVID-19 hospitalized patients and was associated with a small number of mild to moderate clinical adverse effects.
- MeSH
- biopsie metody MeSH
- cyklofosfamid farmakologie terapeutické užití MeSH
- glukokortikoidy farmakologie terapeutické užití MeSH
- hydroxychlorochin farmakologie terapeutické užití MeSH
- kyselina mykofenolová farmakologie terapeutické užití MeSH
- lidé MeSH
- nefritida při lupus erythematodes * diagnóza farmakoterapie MeSH
- proteinurie diagnóza etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Klíčová slova
- remdesivir, favipiravir, podpůrná léčba,
- MeSH
- antivirové látky aplikace a dávkování farmakologie klasifikace MeSH
- COVID-19 * diagnóza ošetřování patofyziologie přenos prevence a kontrola terapie MeSH
- diagnostické techniky a postupy klasifikace MeSH
- farmakoterapie COVID-19 MeSH
- hydroxychlorochin aplikace a dávkování farmakologie MeSH
- imunologické faktory aplikace a dávkování klasifikace MeSH
- lidé MeSH
- prostředky na ochranu dýchání MeSH
- rizikové faktory MeSH
- SARS-CoV-2 patogenita růst a vývoj účinky léků MeSH
- stupeň závažnosti nemoci MeSH
- tekutinová terapie MeSH
- umělé dýchání metody ošetřování MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- antiflogistika nesteroidní farmakologie MeSH
- antifungální látky farmakologie MeSH
- azathioprin farmakologie MeSH
- dermatologické látky * farmakologie MeSH
- dimethyl fumarát farmakologie MeSH
- farmakoterapie MeSH
- glukokortikoidy farmakologie MeSH
- hydroxychlorochin farmakologie MeSH
- imunoglobuliny farmakologie MeSH
- inhibitory fosfodiesterasy 4 farmakologie MeSH
- inhibitory Janus kinas farmakologie MeSH
- inhibitory kalcineurinu farmakologie MeSH
- inhibitory TNF farmakologie MeSH
- interleukin-12 antagonisté a inhibitory fyziologie MeSH
- interleukin-17 antagonisté a inhibitory fyziologie MeSH
- interleukin-23 antagonisté a inhibitory fyziologie MeSH
- keratolytika farmakologie MeSH
- kůže účinky léků MeSH
- lidé MeSH
- methotrexát farmakologie MeSH
- NF-kappa B antagonisté a inhibitory fyziologie MeSH
- receptory cytokinové antagonisté a inhibitory fyziologie MeSH
- receptory kyseliny retinové fyziologie MeSH
- retinoidy farmakologie MeSH
- rituximab farmakologie MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- FEXOFENADIN, MONTELUKAST,
- MeSH
- acetáty farmakologie terapeutické užití MeSH
- angioedém diagnóza MeSH
- chinoliny farmakologie terapeutické užití MeSH
- cystitida diagnóza MeSH
- diferenciální diagnóza MeSH
- hydroxychlorochin farmakologie terapeutické užití MeSH
- imunologické testy MeSH
- klinické laboratorní techniky MeSH
- lidé středního věku MeSH
- lidé MeSH
- sinusitida diagnóza MeSH
- systémový lupus erythematodes * diagnóza farmakoterapie MeSH
- terfenadin analogy a deriváty farmakologie terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Chloroquine, an antimalarial drug, can also be used in the regulation of the immune system, e.g. it is used in the treatment of autoimmune diseases. In this study we investigated the effects of chloroquine and its hydroxy-derivative on nitric oxide (NO) production in two different cell types: (i) immortalized mouse macrophage cell line RAW 264.7 and (ii) mouse bone marrow-derived macrophages (BMDM). The cells were treated with different concentrations (1-100 μM) of chloroquine or hydroxychloroquine and stimulated with lipopolysaccharide for 24 h to induce NO production. Measurement of nitrites by the Griess reaction was used to evaluate the production of NO. Expression of inducible NO synthase was evaluated with Western blot and ATPcytotoxicity test was used to measure the viability of the cells. Our results showed that both chloroquine and its hydroxy-derivative inhibited NO production in both cell types. However, based on the results of LD50 these inhibitory effects of both derivatives were due to their cytotoxicity. The LD50 values for chloroquine were 24.77 μM (RAW 264.7) and 24.86 μM (BMDM), the LD50 for hydroxychloroquine were 13.28 μM (RAW 264.7) and 13.98 μM (BMDM). In conclusion, hydroxychloroquine was more cytotoxic than its parent molecule. Comparing the two cell types tested, our data suggest that there are no differences in cytotoxicity of chloroquine or hydroxychloroquine for primary cells (BMDM) or immortalized cell line (RAW 264.7).
- MeSH
- buňky kostní dřeně účinky léků metabolismus MeSH
- chlorochin chemie farmakologie MeSH
- dusitany metabolismus MeSH
- hydroxychlorochin chemie farmakologie MeSH
- makrofágy účinky léků metabolismus MeSH
- myši MeSH
- oxid dusnatý biosyntéza MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Antimalarika patří mezi základní léčiva, užívaná v revmatologii již více než šedesát let. V roce 1943 byly syntetizovány chlorochin a hydroxychlorochin (HCQ), tedy 4-aminochinolinové deriváty. Od té doby tato skupina antimalarik postupně pronikala do farmakoterapie revmatických onemocnění a v současné době patří k zavedeným a široce používaným antirevmatikům, resp. chorobu modifikujícím lékům (disease modifying drugs – DMARDs).
