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"Combination of epirubicin with the autophagy inhibitor hydroxychloroquine resulted in a significant reduction in tumor growth compared with monotherapy with epirubicin."
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"Herein, we describe our current understanding of the core components of the autophagy machinery, the functional relevance of autophagy within the tumor microenvironment and outline how this knowledge has informed preclinical investigations combining the autophagy inhibitor hydroxychloroquine (HCQ) with chemotherapy, targeted therapy and immunotherapy."
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"Chloroquine (and its derivative hydroxychloroquine) inhibits autophagy, which is the proposed mechanism of its anti-ZIKV action since deficiency in an essential autophagy gene, Atg16l1, in mice limited ZIKV vertical transmission, placental and fetal damage, and improved placental and fetal outcomes overall."
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"Based on the different types of inhibitory analyses, 10mM of the autophagy inhibitor 3-methyladenine (3-MA, Sigma-Aldrich Co., St. Louis, MO, USA), 100nM of the autophagy inhibitor bafilomycin A1 (ba A1, Sigma-Aldrich Co., St. Louis, MO, USA), 50muM of the autophagy inhibitor hydroxychloroquine (Selleck Chemicals, Houston, TX, USA), 5muM of the AKT inhibitor triciribine (Selleck Chemicals, Houston, TX, USA), 5muM of the PI3K agonist insulin like growth factors-1 (IGF-1, R&D Systems, Inc., Minneapolis, USA), 5muM of the PI3K inhibitor LY294002 (Selleck Chemicals, Houston, TX, USA), and 1muM of the mTOR inhibitor rapamycin (Rapa, Selleck Chemicals, Houston, TX, USA) were added to the culture medium together with HSYA for 4h."
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"For these reasons, it is no surprise that autophagy inhibitors such as hydroxychloroquine are actively trialed in the clinic for treatment of cancers and development of novel autophagy inhibitors are earnestly pursued."
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"In fact, the autophagy inhibitor hydroxychloroquine (HCQ) is currently in clinical trials to examine whether co-treatment with HCQ and imatinib offers a therapeutic benefit over imatinib alone [48]."
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"It is thus reasonable to consider a cancer treatment approach that combines traditional anti-cancer chemotherapy with autophagy inhibitors such as hydroxychloroquine."
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"Autophagy inhibitor hydroxychloroquine (HCQ) was used to identify the sensitivity of breast cancer subtypes to autophagy inhibition in the present study."
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"The only autophagy inhibitors whose effectiveness in vivo and safety in clinical trials have been approved by the FDA are chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) that suppress autophagy by blocking autophagosome fusion and degradation."
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"To differentiate this, we treated the MCL cell line Mino with palbociclib and the downstream autophagy inhibitor hydroxychloroquine which inhibits the acidification of lysosomes, completely blocks autophagy in its final step and therefore leads to the accumulation of autophagosomes [XREF_BIBR]."
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"Chi et al. reported a 40% response rate and a 84% disease control rate by simultaneously adding the autophagy inducer rapamycin and the autophagy inhibitor hydroxychloroquine in 25 patients with various tumor types presenting with intrinsic resistance to numerous MC regimens [XREF_BIBR]."
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"ROC-325 exhibited superior in vitro anticancer effects than the existing autophagy inhibitor hydroxychloroquine in 12 different cancer cell lines with diverse genetic backgrounds."
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"Hydroxychloroquine (HCQ), a drug routinely used in the clinical treatment of malaria and autoimmune disorders [XREF_BIBR], is a potent inhibitor of autophagy."
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"Herein, we describe our current understanding of the core components of the autophagy machinery and the functional relevance of autophagy within the tumor microenvironment, and we outline how this knowledge has informed preclinical investigations combining the autophagy inhibitor hydroxychloroquine (HCQ) with chemotherapy, targeted therapy, and immunotherapy."
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"Autophagy inhibition by chloroquine and hydroxychloroquine could adversely affect AKI and other organ injury in critically ill patients with COVID-19."
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"Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer."
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"Hydroxychloroquine inhibits systemic inflammation and autophagy and may thus have antineoplastic effects [1]."
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"[Effect of Autophagy Inhibitor Hydroxychloroquine on Chemosensitivity of Castration resistant Prostate Cancer]."
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"Chloroquine and hydroxychloroquine accumulate within lysosomes and are thought to block autophagy by elevating intralysosomal pH and inhibiting lysosomal enzymes [XREF_BIBR, XREF_BIBR]."
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"In this Phase I/II clinical trial, we establish that preoperative treatment with the autophagy inhibitor hydroxychloroquine in combination with chemotherapy is safe and tolerable."
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"Correction : Hydroxychloroquine Inhibits Autophagy to Potentiate Antiestrogen Responsiveness in ER+ Breast Cancer."
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"Given the overall similar behavior to the autophagy inhibitor hydroxychloroquine (HCQ) (XREF_SUPPLEMENTARY), and that AMPK, CK2 and the PIK3C3 complex II positively regulate autophagy, palbociclib likely also inhibits autophagy."
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"Since bafilomycin A1 could have non-autophagy-related activities, we performed confirmatory experiments with additional autophagy inhibitors including hydroxychloroquine sulfate (lysosomal acidification inhibitor), 3-methyladenine (3-MA, PI3K inhibitor), and MHY1485 (mTOR agonist)."
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"Results : ROC-325 exhibited superior in vitro anticancer effects compared with the existing autophagy inhibitor hydroxychloroquine (HCQ) in 12 different cancer cell lines with diverse genetic backgrounds."
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"Other inhibitors, such as 1) Bafilomycin A 1, a specific inhibitor of vacuolar-type H (+)-ATPases; 2) hydroxychloroquine, a lysosomal lumen alkalizer; and 3) pepstatin A, an inhibitor of acid proteases, have also been used to inhibit complete autophagy."
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"Inhibition of autophagy by hydroxychloroquine, a well tolerated autophagy inhibitor, reduced cell viability in both ETV6-RUNX1 positive cell lines and primary acute lymphoblastic leukemia samples, and selectively sensitized primary ETV6-RUNX1 positive leukemia samples to L-asparaginase."
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"When autophagy was pharmacologically suppressed by hydroxychloroquine , PEDV replication decreased from 8.5 x 105 TCID50 / mL to 7.9 x 104 TCID50 / mL ."
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"Moreover, in vivo inhibition of autophagy by hydroxychloroquine in B16-F10 tumor bearing mice and mice vaccinated with tyrosinase related protein-2 peptide dramatically increased tumor growth inhibition."
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"Antimalarial drugs, chloroquine and hydroxychloroquine, inhibit autophagy and are undergoing clinical trials as antitumor drugs XREF_BIBR."
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"Autophagy was inhibited by hydroxychloroquine (HCQ), whereas the ability of Dex resistant MMcells to recover the susceptibility to apoptosis was measured."
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"XREF_BIBR, XREF_BIBR In addition to its immunomodulatory effects, hydroxychloroquine has been noted to inhibit cellular autophagy."
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"The lysosomotropic agents chloroquine and hydroxychloroquine have been used to impair the autophagy pathway, where their properties as weak bases suppress the degradation of autophagic cargo by lysosomal enzymes."
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"Although a number of studies have demonstrated that autophagy may sensitize certain tumor cells to chemotherapeutic agents [XREF_BIBR - XREF_BIBR], the clinical applications of autophagy inhibitors such as CQ and hydroxychloroquine have been limited by their efficacy and side effects [XREF_BIBR, XREF_BIBR]."
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"Interestingly, a phase 1 clinical trial including patients with relapsed and refractory myeloma showed promising results for the combination of bortezomib with the autophagy inhibitor hydroxychloroquine corroborating our results [XREF_BIBR]."
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"Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8."
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"Autophagy inhibitors, such as chloroquine and hydroxychloroquine, are currently in clinical trials for multiple types of cancer [XREF_BIBR]."
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"Furthermore, preventing the acidification of lysosomes, hydroxychloroquine impairs cellular autophagy, a critical step for innate and adaptive immunity activation [XREF_BIBR]."
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"Notably, we observed that treatment with the autophagy inhibitor hydroxychloroquine reduced T cell mediated tumor killing."
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"Given the divergent conclusions of published studies regarding autophagy protein markers and autophagosome formation, the utility of autophagy inhibitors (lysosomotropic agents) such as chloroquine (CQ) or hydroxychloroquine (HCQ) in clinical trials for melanoma (either alone or as a combination therapy) supports conclusions in the literature that autophagy is a pro survival feature of melanomas, and so inhibiting the process pharmacologically is not only of clinical relevance, but a priority [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"Hydroxychloroquine has been shown to inhibit autophagy, a process by which dying cells recycle injured organelles and internal toxins to generate needed energy for survival and reproduction."
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"Furthermore, unfortunately, single proteasome inhibitor treatment has been proven unsatisfactory for solid tumors in clinical trials.5, 6 A recent clinical trial suggested that the anticancer effect of Bor is enhanced when it is combined with an autophagy inhibitor.7 To date, autophagy inhibitors including hydroxychloroquine (HCQ) and chloroquine (CQ) have been clinically viable."
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"Accordingly, selective triple knockdown of the autophagy genes ATG7, ATG5 and ATG3, and pretreatment with the autophagy inhibitor hydroxychloroquine, efficiently overcame the resistance to Akt and mTOR inhibitors, leading to the activation of the mitochondrial apoptotic pathway."
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"Autophagy was involved in doxorubicin induced resistance of myeloma cell line RPMI8226, DOX resistance in myeloma cells was reversed partly by autophagy inhibitor hydroxychloroquine or 3-MA, and autophagy may be one of mechanisms for drug resistance."
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"XREF_BIBR - XREF_BIBR It is thus seemingly paradoxical that hydroxychloroquine, an anti-malarial drug that blocks autophagy by raising intralysosomal pH, is under evaluation in multiple cancer trials (XREF_TABLE)."
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"In addition to the existing autophagy inhibitors such as hydroxychloroquine and chloroquine, which are approved for treatment of malaria by US FDA, identification of novel and highly effective autophagy inhibitors is obviously needed."
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"Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), which are clinically used antimalarial drugs, also inhibit autophagy by preventing the acidification of the lysosomal compartment XREF_BIBR."
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"These findings are currently under clinical investigation with several studies examining whether pharmacologic inhibition of autophagy with the anti-malaria and non specific autophagy inhibitor hydroxychloroquine augments the efficacy of standard anticancer regimens [XREF_BIBR - XREF_BIBR]."
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"Similar to previously published data, treatment with the prototypical autophagy inducer rapamycin increased ZIKV titers whereas the prototypical autophagy inhibitor hydroxychloroquine decreased titers [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"Hydroxychloroquine has been shown to inhibit autophagy."
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"Moreover, a study using murine endometriosis model revealed that inhibition of autophagy by hydroxychloroquine effectively promotes apoptosis of human endometriotic cells and decreases the number of endometriotic lesions."
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"Meanwhile, autophagy inhibition by 3-methyaldenine (3-MA) and hydroxychloroquine, as well as by siRNA knocking down of Beclin-1 or ATG-7, inhibited AZD-2014-induced cytotoxicity, while the apoptosis inhibitor had no rescue effect."
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"Finally, administration of vemurafenib with the autophagy inhibitor hydroxychloroquine promoted more pronounced tumor suppression in vivo."
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"Hydroxychloroquine (HCQ) inhibits lysosomal acidification and blocks autophagy via influencing autophagosome fusion and degradation."
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"The antimalarial drug hydroxychloroquine blocks autophagy, inhibits the growth of cancer cells, and induces cell death [XREF_BIBR] (see XREF_FIG)."
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"In light of the sensitizing effect of autophagy inhibition on chemotherapy induced cell death, a number of clinical trials have been launched combining the first generation autophagy inhibitor hydroxychloroquine (HCQ) with individual chemotherapeutic agents in patients with solid tumors."
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"Hydroxychloroquine and chloroquine inhibits autophagy by entering the lysosomes (lysosomotropic) and changing the acidity through chelating protons."
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"Thus, the effect of the autophagy inhibitor Hydroxychloroquine (HCQ) on B16-F10 tumor growth was evaluated alone or in combination with a Tyrosinase Related Protein-2 (TRP2) peptide based vaccination strategy."
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"During the later stages of tumor progression, autophagy is thought to be important for tumor cell survival such that autophagy inhibitors like chloroquine or hydroxychloroquine can sensitize certain cells to chemotherapeutic agents [XREF_BIBR, XREF_BIBR - XREF_BIBR]."
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"When autophagy was pharmacologically suppressed by hydroxychloroquine, PEDV replication decreased from 8.5 x10 5 TCID 50 / mL to 7.9 x10 4 TCID 50 / mL."
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"Fortuitously, the autophagy inhibitor hydroxychloroquine (a chloroquine derivative) has been used for many years in the management of patients with systemic lupus erythematosus, rheumatoid arthritis and malaria and therefore information about dosage, safety and side-effects has been available."
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"AML CD34 + cells were more sensitive to the autophagy inhibitor hydroxychloroquine (HCQ) than normal bone marrow CD34 + cells."
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"The effects of autophagy on cell proliferation and apoptosis were studied by autophagy inhibitor hydroxychloroquine (HCQ) and autophagy promoter Rapamycin."
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"Next, we tested the effects of hydroxychloroquine (HCQ), which inhibits autophagy by impairing the lysosomal acidification of the autophagic cargo, blocking the fusion of autophagosomes with lysosomes [XREF_BIBR]."
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"Unlike the autophagy inhibitor hydroxychloroquine, however, Y100 treatment does not result in accumulation of lipidated LC3B (LC3B-II), suggesting that it causes p62 accumulation via a distinct mechanism."
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"Autophagy inhibitors, such as chloroquine and hydroxychloroquine, have already been clinically approved, promoting drug combination treatment by targeting autophagic pathways as a means of discovering and developing more novel and more effective cancer therapeutic approaches."
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"Autophagy inhibition by hydroxychloroquine (HCQ) reduced the effect of nilotinib in vivo."
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"Autophagy inhibitor hydroxychloroquine (HCQ), ERK1/2 inhibitor U0126 and AKT inihbitor MK-2206 were obtained from Selleck Chemicals LLC (Houston, TX, USA)."
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"Furthermore, high glucose induced autophagy in ARPE-19 with the treatment of glucose for 48h, and autophagy inhibitor hydroxychloroquine (HCQ) or bafilomycin further aggravated the senescence, accompanying by an increase in oxidant species."
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"On other hand, CQ, Hydroxychloroquine, and Bafilomycin A inhibit autophagy at late stages by suppressing the lysosomal function XREF_BIBR - XREF_BIBR."
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"Xie et al. showed that mTOR dependent melanoma cells can be driven to apoptosis when treated with the mTOR inhibitor temsirolimus and the autophagy inhibitor hydroxychloroquine."
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"Hydroxychloroquine inhibits systemic inflammation and autophagy and may thus have antineoplastic effects [XREF_BIBR]."
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"Bafilomycin A1 and hydroxychloroquine inhibit autophagy by preventing the fusion of autophagosomes and lysosomes."
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"To see whether autophagy inhibition improves the efficacy of PI3K inhibitor in PIK3CA-mutant cancer cells, cells were treated with BKM120, a pan-PI3K inhibitor, and the autophagy inhibitor hydroxychloroquine (HCQ)."
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"We also showed that treatment with the autophagy inhibitor hydroxychloroquine (HCQ) significantly decreased the cell viability of Ad-Fhit-infected H460 cells."
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"We also found that the lysosomotropic agent and autophagy inhibitor hydroxychloroquine (HCQ) synergizes with CCI-779 and led to melanoma cell death via apoptosis."
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"Adding hydroxychloroquine that inhibits autophagy would make it more difficult to clear the hydrogen peroxide, leading to quicker cell death."
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"Based on the successful experimental findings in vitro and in vivo, clinical trials of autophagy inhibitor such as hydroxychloroquine in combination with chemotherapy in patients with blood cancers are currently underway."
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"We here demonstrate that hydroxychloroquine preferentially induces apoptosis of CD45RO+ memory and effector T cells by inhibiting the survival pathway of autophagy."
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"Rapamycin and its analogs are strong inducers of autophagy by inhibiting mTOR activity, and hydroxychloroquine can inhibit autophagy by blocking the fusion of autophagosomes with lysosomes."
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"The latest reports have shown that the autophagy inhibitor hydroxychloroquine is tolerable and potentially effective in combination with the MTOR targeted agent temsirolimus XREF_BIBR and the proteasome inhibitor bortezomib XREF_BIBR in phase I trials and may be a valid complement to STAT3 targeted therapy."
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"Interestingly, HLTF was found to be one of the genetic determinants conferring sensitivity or resistance to lysosomal autophagy inhibitors such as hydroxychloroquine (HCQ) in several cancer cell lines XREF_BIBR."
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"Classic autophagy inhibitors such as chloroquine and hydroxychloroquine have been introduced into phase I/II clinical trials, while more experimental compounds are moving forward in preclinical development."
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"Hydroxychloroquine (HCQ) has been shown to disrupt autophagy and sensitize cancer cells to radiation and chemotherapeutic agents."
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"The most recent reports have shown that the autophagy inhibitor hydroxychloroquine is tolerable and potentially effective in combination with the MTOR targeted agent temsirolimus [XREF_BIBR] and the proteasome inhibitor bortezomib [XREF_BIBR] in phase I trials (www.clinicaltrials.gov)."
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"Here, effects of the autophagy inhibitor hydroxychloroquine (HCQ) and activator LiCl on postharvest jujube fruit senescence were investigated."
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"Additionally, hydroxychloroquine, a derivative of chloroquine, has been shown to inhibit autophagy in cancer cells and restore sensitivity to ER pathway inhibitors, such as tamoxifen, in ER positive cancer cells [XREF_BIBR]."
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"Recently, a phase I/II study in patients with glioblastoma multiforme showed that hydroxychloroquine could inhibit autophagy in vivo [XREF_BIBR]."
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"Hydroxychloroquine (HCQ) inhibits autophagy."
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"The pharmacological targeting of control points of the autophagy system by combining established cancer treatments with autophagy inhibitors such as Atg5/7 silencing or hydroxychloroquine was presented by Professor Eileen White of Rutgers University (NJ, USA)."
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"In contrast, the autophagy inhibitors hydroxychloroquine (HCQ), 3-methyladenine (3-MA), and bafilomycin A1 (BafA1) prevented ENT1 degradation and enhanced RBV antiviral activity."
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"To explore potential anti-melanoma activity of systemic autophagy deficiency, pharmacologic inhibition (as opposed to genetic ablation), of autophagy was tested by administration of the lysosomal autophagy inhibitor hydroxychloroquine (HCQ)."
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"In fact, the autophagy inhibitor hydroxychloroquine (HCQ) is currently in clinical trials to examine whether co-treatment with HCQ and imatinib offers a therapeutic benefit over imatinib alone [XREF_BIBR]."
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"Rapamycin can inhibit the proliferation, induce apoptosis and autophagy of RPMI 8226, the hydroxychloroquine can inhibit autophagy and proliferation of RPMI 8226, and induce apoptosis, the 3-MA can inhibit autophagy of RPMI 8226, but hardly has any effects on proliferation and apoptosis of RPMI 8226 cells."
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"Autophagy inhibitors such as 3-MA (a class-III-PI3K inhibitor), bafilomycin A1, hydroxychloroquine and monensin (autophagosome-lysosome fusion inhibitors) have shown different efficacies in mitigating the effects of chemo- and radiotherapeutic anti-cancer treatments [XREF_BIBR], indicating the complexity with which this process is executed."
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"Chloroquine and hydroxychloroquine accumulate within lysosomes and are thought to block autophagy through elevation of intralysosomal pH and inhibition of lysosomal enzymes XREF_BIBR, XREF_BIBR."
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"Consistent with this hypothesis, a cytoprotective role of autophagy in established tumors exposed to stressors like anticancer treatments is suggested in studies where autophagy inhibitors like hydroxychloroquine or 3-methyladenine (3-MA) sensitize cancer cells to treatments like tamoxifen treatment, radiation, DNA alkylating agents cylophosphamide and cisplatin, and tyrosine kinase receptor inhibitor imatinib."
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"Furthermore, inhibition of autophagy by hydroxychloroquine (HCQ) or shRNA targeting BECN or Atg5 led to increased sensitivity to GCB in LM7 OS cells and decreased sensitivity to GCB in the CCH-OS-D and K7M3 cells, confirming the dual role of autophagy in OS."
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"In contrast, the autophagy inhibitors hydroxychloroquine (HCQ), 3-methyladenine (3-MA), and bafilomycin A1 (BafA1) prevented ENT1 degradation and enhanced RBV antiviral activity."
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"Therefore, autophagy inhibitors, such as chloroquine or hydroxychloroquine, have a therapeutic potential in cancer treatment XREF_BIBR - XREF_BIBR."
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"In a relevant clinical trial in dogs with non Hodgkin 's lymphoma, the combined treatment of autophagy inhibitor hydroxychloroquine (12.5 mg/kg/d) with a lower dose of doxorubicin (25 mg/m 2) has resulted in clinical benefit with superior overall response rate (93.3%) and comparable median progression-free interval (5 months) compared to standard single agent doxorubicin (30 mg/m 2) treatment [XREF_BIBR]."
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"Chloroquine (CQ) and hydroxychloroquine (HCQ) are known to inhibit autophagy and have been investigated in preclinical studies and in more than 30 clinical trials; however, the ocular toxicities and minimal single-agent anticancer efficacy of CQ or HCQ have restricted their clinical application."
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"Appropriate interpretation of the outcomes of these trials would require knowledge as to whether the drugs or radiation used promote the cytoprotective form of autophagy in the tumor cells as well as whether the chloroquine or hydroxychloroquine actually inhibit the autophagy."
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"Autophagy inhibitors such as 3-MA and hydroxychloroquine sensitize tumors to the anti-cancer drugs, while autophagy inducers like rapamycin inhibits tumor proliferation 44 and sensitizes tumors to the radiation 45."
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"We thus conducted a first-in-human study to investigate the safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the combination of the autophagy inhibitor hydroxychloroquine (HCQ) and VOR in patients with advanced solid tumors."
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"Here we demonstrate that in human T cells there is a basal level of autophagy and that the inhibition of autophagy by hydroxychloroquine induces apoptosis."
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"Moreover, current clinical trials use the autophagy inhibitor hydroxychloroquine for treatment of a wide range of cancers, with promising results [XREF_BIBR - XREF_BIBR]."
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"The autophagy inhibitors such as hydroxychloroquine (HCQ), 3-methyladenine (3-MA) might be helpful to restore the sensitivity of the resistant cells to Lapatinib via abolishing the formation process and degradation ability of autophagosome [33,34]."
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"The PEDV yield was suppressed when autophagy was inhibited by hydroxychloroquine at an early stage, while the viral titers were increased when autophagy was induced by rapamycin."
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"Based on such evidence, clinical trials are underway in which various cancers are being treated with a combination of existing anticancer drugs and autophagy inhibitors such as chloroquine and hydroxychloroquine XREF_BIBR XREF_BIBR."
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"Two antimalarial drugs, CLQ and hydroxychloroquine, inhibited the autophagy induced by p53 mediated apoptosis and augmented the anticancer activity of cyclophosphamide in Myc driven lymphoma [XREF_BIBR, XREF_BIBR]."
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"We investigated the effects of the autophagy inhibitor hydroxychloroquine (HCQ) on cell death of cytosine arabinoside (Ara-C)-resistant human acute myeloid leukemia (AML) cells."
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"We have explored the ability of hydroxychloroquine (HCQ), which inhibits autophagy, to affect antiestrogen responsiveness."
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"Hydroxychloroquine preferentially induces apoptosis of CD45RO+ effector T cells by inhibiting autophagy : A possible mechanism for therapeutic modulation of T cells."
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"Lysosomal autophagy inhibitors (LAI) such as hydroxychloroquine (HCQ) have significant activity in a subset of cancer cell lines."
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"Recent studies showed that hydroxychloroquine can inhibit the latter step of autophagy and therefore enhance the anti-glioma efficiency of ZD6474, a tyrosine kinase inhibitor."
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"Although some clinical successes have been noted with chloroquine, a phase I/II clinical trial with the autophagy inhibitor hydroxychloroquine administered in combination with standard and adjuvant chemoradiotherapy failed to show a significant benefit in patients with newly diagnosed GBM."
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"This is in accordance with the recent clinical trial showing dose dependent inhibition of autophagy by hydroxychloroquine in GBM patients and suggests that dosing needs to be adapted to the specific patient tumour."
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"Appropriate interpretation of the outcomes of these trials would require knowledge as to whether the drugs or radiation utilized promote the cytoprotective form of autophagy in the tumor cells as well as whether the chloroquine or hydroxychloroquine actually inhibited the autophagy."
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"As discussed above, current autophagy inhibitors, such as chloroquine, hydroxychloroquine, and bafilomycin A1, mainly inhibit lysosomal functions."
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"Autophagy inhibitor hydroxychloroquine sulfate (HCQ) was obtained from Tokyo Chemical Industry (Japan)."
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"Chloroquine and hydroxychloroquine inhibit autophagy at a late stage by blocking lysosomal acidification resulting in an inability to digest its engulfed cargo."
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"A significant decrease in tumor growth in mice treated with the autophagy inhibitor hydroxychloroquine (HCQ) was reported 53."
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"Interestingly, in vivo administration of the autophagy inhibitor hydroxychloroquine (HCQ) with a tyrosinase related protein-2 (TRP2) peptide based vaccination strategy led to a significant reduction of melanoma growth compared to vaccine or HCQ treatment alone."
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"Autophagy inhibition by chloroquine and hydroxychloroquine could adversely affect AKI and other organ injury in critically ill patients with COVID-19."
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"We have previously shown that autophagy is rapidly induced following TKI treatment in CML cells and pharmacological autophagy inhibition, using the nonspecific autophagy inhibitor hydroxychloroquine (HCQ; inhibits autophagy at a late stage by preventing the fusion of autophagosomes and lysosomes), enhances the effect of TKI treatment in CML cells, including primary CD34 + stem or progenitor cells."
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"Similarly, the effects of 5-FU are augmented in colon cancer when treated with autophagy inhibitor hydroxychloroquine (HCQ)."
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"Currently, autophagy inhibitors such as CQ and hydroxychloroquine (HCQ) are under investigation in clinical phase I/II for various cancers including lung cancer [XREF_BIBR, XREF_BIBR]."
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"Consistent with these findings, we show that Tat protein levels increase dramatically in cells with the autophagy inhibitor hydroxychloroquine, which permeabilizes lysosomal membranes, blocking both macroautophagy as well as chaperone mediated autophagy."
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"Blockade of autophagy by hydroxychloroquine (HCQ) potentially enhances the KG-135-mediated increase of FOXO3a and its downstream death receptor ligand Fas ligand (FasL), as well as the decrease of survivin and Bcl-2, resulting in massive apoptosis."
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"We performed a randomized controlled trial to assess the autophagy inhibitor hydroxychloroquine in combination with gemcitabine and nab-paclitaxel."
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"Autophagy inhibitors such as hydroxychloroquine are being tested in a number of clinical trials as a chemo sensitizer."
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"The results of this study are predicted to show that hydroxychloroquine effectively reduces autophagy in tumor cells and make them more likely to undergo cell death in the hypoxic environment since the main survival mechanism of the tumor cells is eliminated."
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"The antimalarial drugs chloroquine and hydroxychloroquine inhibit autophagy, leading to increased cytotoxicity in combination with several anticancer drugs in preclinical models."
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"Currently, the only FDA approved agents able to inhibit autophagy are chloroquine, an anti-malaria drug, and its derivative hydroxychloroquine, which block autophagy by disrupting lysosome acidification."
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"Given recent studies demonstrating that autophagy is a resistance mechanism to multiple therapeutic agents in the setting of apoptotic inhibition, we hypothesized that hydroxychloroquine (HCQ), an anti-malarial drug that inhibits autophagy, will increase cytotoxicity of ABT-737."
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"XREF_BIBR, XREF_BIBR Chloroquine and hydroxychloroquine can inhibit autophagy induced by p53 controlled apoptosis in Myc driven lymphoma and augmented the anticancer activity of cyclophosphamide."
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"Our previous work demonstrated that co-treatment with the autophagy inhibitor hydroxychloroquine (HCQ) could effectively block the last step of autophagy and enhance cell death induced by activation of p53 or treatment with alkylating chemotherapy in a model of Myc induced tumorigenesis."
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"In this regard, we also show that treatment of mice with the autophagy inhibitor hydroxychloroquine, which is currently being used in several clinical trials, significantly accelerates tumour formation in mice containing oncogenic Kras but lacking p53."
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"More recently, two second generation autophagy inhibitors, Lys05 a highly potent lysosometric agent and PIK-III a selective inhibitor of VPS34, demonstrated synergistic effects with TKIs to reduce primary CML LSCs quiescence, compared to the first generation autophagy inhibitor Hydroxychloroquine [XREF_BIBR]."
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"Recently, preclinical studies demonstrated that autophagy inhibition by hydroxychloroquine augments the efficacy of the proteasome inhibitor bortezomib in myeloma, indicating that the combination of autophagy and proteasome inhibition might be clinically useful for improving the outcomes of this neoplasia [XREF_BIBR, XREF_BIBR]."
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"Hydroxychloroquine (HCQ) inhibits autophagy and therefore can sensitize some cancer cells to chemotherapy, but the high doses required limit its clinical use."
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"When autophagy was pharmacologically suppressed by hydroxychloroquine , PEDV replication decreased from 8.5 x 10 5 TCID 50 / mL to 7.9 x 10 4 TCID 50 / mL ."
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"Research has shown that treatment with the autophagy inhibitor hydroxychloroquine reduces the incidence of ZIKV vertical transmission in pregnancy."
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"Furthermore, selective triple knockdown of the autophagy genes ATG7, ATG5 and ATG3, and pre-treatment with the autophagy inhibitor hydroxychloroquine, efficiently overcame the resistance to Akt and mTOR inhibitors in this model, leading to the activation of the mitochondrial apoptotic pathway."
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"The lysosomotropic agent hydroxychloroquine (HCQ), has been shown to inhibit autophagy in preclinical cancer models XREF_BIBR."
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"Vorinostat and hydroxychloroquine improve immunity and inhibit autophagy in metastatic colorectal cancer."
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"HeLa cells exposed to the autophagy inhibitors hydroxychloroquine, bafilomycin A1, and monensin displayed increased mitochondrial cell death."
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"Inhibition of autophagy by hydroxychloroquine enhances antioxidant nutrients and delays postharvest fruit senescence of Ziziphus jujuba."
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"Autophagy flux induced by apelin-13 was inhibited by NAC and catalase but not hydroxychloroquine (HCQ)."
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"Introduction Hydroxychloroquine ( Plaquenil ) is an aminoquinoline that is commonly used to treat malaria and a variety of rheumatic and dermatologic diseases , including systemic lupus erythematosus , rheumatoid arthritis , Sjogren syndrome , and porphyria cutanea tarda.1 ,2 In addition to its immunomodulatory effects , hydroxychloroquine has been noted to inhibit cellular autophagy ."
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"Multiple trials using relatively nonspecific autophagy inhibitors, such as chloroquine and hydroxychloroquine, have been launched for the treatment of cancer."
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"For example, there are currently almost 3 dozen clinical trials in the U.S. attempting to block the cellular survival functions of autophagy in cancer treatment by combining chemotherapy with the autophagy inhibitor hydroxychloroquine."
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"Furthermore, because patients with Copa syndrome show an increase in autophagy with abnormal autophagosomes, hydroxychloroquine, which prevents autophagy by inhibiting lysosomal acidification and impairing fusion of the autophagosome with the lysosome, may also be useful for therapy for Copa syndrome."
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"To assess the functional importance of increased levels of autophagy observed in aggressive compared to indolent melanoma spheroids, spheroids were treated with PBS or a low dose of the autophagy inhibitor hydroxychloroquine."
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"To differentiate this, we treated the MCL cell line Mino with palbociclib and the downstream autophagy inhibitor hydroxychloroquine which inhibits the acidification of lysosomes, completely blocks autophagy in its final step and therefore leads to the accumulation of autophagosomes [XREF_BIBR]."
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"To further test which pathway is responsible for the decreased LC3-II levels (XREF_FIG), we incubated cells with hydroxychloroquine (CQ), which blocks lysosome acidification and thereby autophagic influx and degradation of LC3-II."
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"Compounds such as chloroquine and hydroxychloroquine that prevent acidification of the lysosomal compartment are the sole clinically available inhibitors of autophagy."
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"8 This suggests that hydroxychloroquine (HCQ), which inhibits endosomal acidification required for optimal TLR signalling 9 and is a medication used by patients with systemic lupus erythematosus (SLE) even during pregnancy, may prevent cardiac injury."
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"The chloroquine derivative hydroxychloroquine (HCQ) inhibits the acidification of lysosomes and shows promising results when combined with gemcitabine."
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"Acidification of lysosomes and function of TLR-7 and TLR-9 are inhibited by hydroxychloroquine, and its activation and release of cytokines is suppressed by prednisone."
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"XREF_BIBR, XREF_BIBR In addition, the widely used antimalarial and anti-inflammatory drugs chloroquine (CQ) and hydroxychloroquine (HCQ), which block lysosomal acidification and degradation, have side effects including retinopathy (bull 's eye maculopathy) and vision loss."
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"Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), which are clinically used antimalarial drugs, also inhibit autophagy by preventing the acidification of the lysosomal compartment XREF_BIBR."
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"Chloroquine and hydroxychloroquine are antimalarial drugs and block lysosomal acidification and degradation of autophagosomes, acting as autophagy inhibitors."
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"Hydroxychloroquine (HCQ), which inhibits lysosomal acidification, negatively impacts both autophagy and macropinocytosis dependent scavenging and is currently under investigation for its cancer therapeutic potential."
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"Chloroquine and hydroxychloroquine prevent the endosomal acidification and fusion in pDCs and also inhibit IDO, a regulator of T-cell responses [XREF_BIBR]."
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"IFNalpha production by SLE-IC can be inhibited by blocking FcRgamma mediated uptake of IgG, by hydroxychloroquine, which increases the intracytoplasmic pH and prevents acidification and maturation of endosomes, or by C-reactive protein, which binds apoptotic cells and nucleoprotein auto-antigens."
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"Two anti-malarial drugs, hydroxychloroquine (HCQ) and chloroquine (CQ), can inhibit lysosomal acidification and prevent the degradation of autophagosomes, thereby suppressing autophagy in Myc driven lymphoma and increasing the antitumor effects of cyclophosphamide XREF_BIBR - XREF_BIBR."
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"Hydroxychloroquine inhibits activation of endosomal NA sensors including TLR7 probably by preventing acidification of endosome, which is required for optimal NA recognition by endosomal NA sensors."
reach
"Currently, hydroxychloroquine (HCQ), which blocks lysosome acidification and autophagosome degradation, is available as an autophagy inhibitor that will enable assessment of the utility of this approach."
reach
"Hydroxychloroquine (HCQ) inhibits lysosomal acidification and blocks autophagy via influencing autophagosome fusion and degradation."
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"50 For example, chloroquine and hydroxychloroquine, routinely used for the treatment of diverse diseases, inhibit lysosomal acidification and prevent autophagy."
reach
"Hydroxychloroquine (HCQ), a lysosomotropic agent, can prevent endosomal acidification and block autophagosome-lysosome fusion."
reach
"Therefore, hydroxychloroquine, which inhibits endosomal acidification required for optimal Toll like receptor signaling, is suggested as a preventive medication for fetal cardiac injury in patients with autoimmune disorders [XREF_BIBR XREF_BIBR]."
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"XREF_BIBR As described, hydroxychloroquine inhibits acidification of intracellular vesicles, and in vitro studies clearly document the inhibition of IFN production induced by nucleic acid containing immune complexes by chloroquine."
| 14 2
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"Hydroxychloroquine inhibits systemic inflammation and autophagy and may thus have antineoplastic effects [XREF_BIBR]."
eidos
"In patients with COVID-19 , hydroxychloroquine decreases the inflammatory response and cytokine storm , but overdose causes toxicity and mortality ."
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"We conducted a pilot study in Kenya with the objectives of assessing if the non steroidal anti-inflammatory drugs acetylsalicylic acid (ASA) or hydroxychloroquine (HCQ) could reduce T cell IA, HIV target cell numbers and inflammation at the genital tract."
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"Therefore, if this unique immune quiescent state can be pharmacologically induced locally, it will provide an excellent women oriented strategy against HIV infection To our knowledge, this is the first research article evaluating in vivo, an innovative trackable implant that can provide controlled delivery of hydroxychloroquine (HCQ) to successfully attenuate vaginal T lymphocyte activation and inflammation in a rabbit model as a potential strategy to induce an " immune quiescent " state within the FGT for the prevention of HIV infection."
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"Hydroxychloroquine (HCQ) has been used for many years to reduce inflammation in the treatment of patients with multiple rheumatologic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)."
reach
"Hydroxychloroquine inhibits systemic inflammation and autophagy and may thus have antineoplastic effects [1]."
eidos
"Hydroxychloroquine ( HCQ ) has long been used to reduce inflammation in patients with RA and lupus ."
reach
"Hydroxychloroquine (HCQ) has long been used to reduce inflammation in patients with RA and lupus."
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"Two potential pathways were inferred to be involved in the protective effect of hydroxychloroquine in CAD : (a) hydroxychloroquine may activate ERK5 (encoded by MAPK7) to prevent endothelial inflammation via inhibition of cell adhesion molecule expression 24; and (b) hydroxychloroquine may inhibit endosomal activation of NADPH oxidase in response to pro inflammatory agonists (TNF-alpha and IL-1beta) and may decrease production of pro inflammatory cytokines in stimulated immune cells 25."
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"We hypothesized that the daily administration of low doses of acetylsalicylic acid (ASA 81mg) or hydroxychloroquine (HCQ 200mg) would reduce inflammation thereby decreasing HIV target cells at the FGT."
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"Hydroxychloroquine, an original antimalarial drug, prevents inflammation caused by lupus erythematosus and rheumatoid arthritis."
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"In patients with COVID-19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality."
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"Mice with MC903 and OVA mediated EoE like inflammation were treated with hydroxychloroquine (HCQ), a lysosomotropic agent that prevents autophagic flux by impairing AV-lysosome fusion."
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"Hydroxychloroquine reverses the prothrombotic state in a mouse model of antiphospholipid syndrome : Role of reduced inflammation and endothelial dysfunction."
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"Additional risk factors may include longer duration of disease and lower likelihood of treatment with prednisone, cyclophosphamide, or hydroxychloroquine [XREF_BIBR], a combination that may promote persistent inflammation leading to vascular tissue damage and induction of CVD."
reach
"Two potential pathways were inferred to be involved in the protective effect of hydroxychloroquine in CAD : (a) hydroxychloroquine may activate ERK5 (encoded by MAPK7) to prevent endothelial inflammation via inhibition of cell adhesion molecule expression 24; and (b) hydroxychloroquine may inhibit endosomal activation of NADPH oxidase in response to pro inflammatory agonists (TNF-alpha and IL-1beta) and may decrease production of pro inflammatory cytokines in stimulated immune cells 25."
| 12 2
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"Flow cytometry was applied to detect changes in apoptosis of RPMI8226 and DOX cells (stained with annexin-V and propidium iodide) caused by inhibition by hydroxychloroquine and 3-methyladenine on autophagy."
reach
"Chloroquine and Hydroxychloroquine Trigger Apoptosis and Inhibit CXCL12 Mediated Proliferation and Anti-Apoptosis."
reach
"This is based on the experiments with bafilomycin A 1 / hydroxychloroquine, in which we showed that autophagy prevented cells from undergoing DOC induced apoptosis, but not from DOC induced necrosis."
eidos
"It might therefore impact on innate immunity-induced immune hyperactivation.A recent study showed that hydroxychloroquine selectively induces apoptosis in the memory T-cell compartment ( CD45RA - CD45RO + ) [ 45 ] ."
eidos
"A recent study showed that hydroxychloroquine selectively induces apoptosis in the memory T-cell compartment ( CD45RA - CD45RO + ) [ 45 ] ."
reach
"Second, our results indicate that chloroquine and hydroxychloroquine abrogate CXCL12 mediated anti-apoptosis (XREF_FIG), wherein pretreatment with chloroquine or hydroxychloroquine increased apoptosis in PANC-1 cells."
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"Hydroxychloroquine induced apoptosis of chronic lymphocytic leukemia involves activation of caspase-3 and modulation of Bcl-2/bax/ratio."
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"Baf was shown to prevent accumulation of the phospholipogenic compound hydroxychloroquine in Hela cells and reduced apoptosis caused by hydroxychloroquine treatment [XREF_BIBR]."
reach
"Hydroxychloroquine preferentially induces apoptosis of CD45RO+ effector T cells by inhibiting autophagy : A possible mechanism for therapeutic modulation of T cells."
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"Mitochondrial membrane permeabilization is a critical step of lysosome initiated apoptosis induced by hydroxychloroquine."
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"We here demonstrate that hydroxychloroquine preferentially induces apoptosis of CD45RO+ memory and effector T cells by inhibiting the survival pathway of autophagy."
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"Mouse embryonic fibroblasts lacking the expression of both Bax and Bak are resistant against hydroxychloroquine induced apoptosis."
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"In contrast, apoptosis induced by hydroxychloroquine (HCQ) in HL-60 cells was caspase-3 independent and was fully inhibited by ATA."
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"Hydroxychloroquine sulphate inhibits in vitro apoptosis of circulating lymphocytes in patients with systemic lupus erythematosus."
14 |
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| 11
| 8
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"Hydroxychloroquine also inhibited CpG induced production of interleukin-6 and tumor necrosis factor-alpha in B cell subsets."
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"Hydroxychloroquine inhibited production of IL-1-alpha (monocytes) and IL-6 (T cells and monocytes)."
reach
"In two clinical trials conducted in the 1990s, Sperber et al. reported suppressive effects on immune activation (measured at that time as IL-6 production) and viral load in individuals treated with 800mg of hydroxychloroquine and day (bioequivalent to 500mg/day of chloroquine) [XREF_BIBR, XREF_BIBR]."
reach
"It is reported that hydroxychloroquine may reduce TNF, interleukin-1 and interleukin-6 production though the consistency and mechanisms of this effect are uncertain."
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"CONCLUSIONS Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication."
reach
"Furthermore, considering that the levels of systemic inflammation biomarkers significantly decreased among good responders in our study, it is notable that methotrexate alone or in combination with sulfasalazine reduces circulating levels of IL-6 [XREF_BIBR], and hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production from PBMC [XREF_BIBR]."
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"Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication."
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"Hydroxychloroquine reduces IL-6 and pro thrombotic status."
Hydroxychloroquine decreases the amount of IL6.
| 2
Hydroxychloroquine decreases the amount of IL6. 2 / 2
| 2
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"In another single-arm study, administration of hydroxychloroquine to HIV infected persons who experienced suboptimal CD4 T-cell gains after highly active antiretroviral therapy (HAART) resulted in decreased levels of T-cell activation and decreased levels of inflammatory cytokines IL-6 and TNF in plasma."
reach
"Additionally, in a monocytic cell line, hydroxychloroquine attenuated TNF-alpha and IL6 expression in response to IL-1beta and TNF-alpha stimulation, respectively 46."
Hydroxychloroquine activates IL6.
| 1
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"Hydroxychloroquine reversed the aPL-inhibition of trophoblast IL-6 secretion and partially limited aPL-inhibition of cell migration."
| 9
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"The antimalarial hydroxychloroquine (HCQ) is frequently used for the treatment of SLE and is supposed to inhibit the conversion of 25 (OH) D in 1,25 (OH) 2 D by inhibiting the enzyme hydroxylase alpha1."
reach
"In contrast, within 5 days 400 mg of hydroxychloroquine daily lowered elevated levels of calcium and 1,25-(OH) 2D by 37% and 72%, respectively, in a hypercalcemic patient with sarcoidosis."
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"Hydroxychloroquine is suspected to inhibit the conversion of 25 (OH) D to its more biologically active form 1,25 (OH) 2 D but has also been found to protect against vitamin D deficiency."
reach
"Hydroxychloroquine has been suspected to inhibit the conversion of 25 (OH) D to its biologically more active form 1,25-dihydroxyvitamin D, and as such, Ruiz-Irastorza et al reported that hydroxychloroquine was associated with higher 25 (OH) D levels."
reach
"Hydroxychloroquine prescribed in several autoimmune diseases may inhibit the conversion of 25 (OH) D to 1,25 (OH) 2 D."
reach
"Huisman and al. found lower 1,25 (OH) 2D concentration in SLE patients treated with hydroxychloroquine and no significant difference in 25 (OH) D concentration among patients who use hydroxychloroquine and those who did not [XREF_BIBR]."
Hydroxychloroquine increases the amount of hydroxide.
| 1
Hydroxychloroquine increases the amount of hydroxide. 1 / 1
| 1
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"XREF_BIBR Our data disclosed two apparent contradictions : antimalarials seemed to be a predictor of lower 25 (OH) D levels; hydroxychloroquine is known to inhibit the 1alpha hydroxylation of 25 (OH) D, thus decreasing the levels of 1,25 (OH) 2D."
Hydroxychloroquine dehydroxylates hydroxide.
| 1
Hydroxychloroquine leads to the dehydroxylation of hydroxide. 1 / 1
| 1
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"XREF_BIBR Our data disclosed two apparent contradictions : antimalarials seemed to be a predictor of lower 25 (OH) D levels; hydroxychloroquine is known to inhibit the 1alpha hydroxylation of 25 (OH) D, thus decreasing the levels of 1,25 (OH) 2D."
| 1
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"On the other hand, Ruiz-Irastroza and al. found higher 25 (OH) D concentration in SEL patients who were treated with hydroxychloroquine [XREF_BIBR]."
Hydroxychloroquine affects SARS-CoV-2
| 7 2
Hydroxychloroquine inhibits SARS-CoV-2. 9 / 9
| 7 2
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"Because of a study showing that chloroquine and hydroxychloroquine inhibit SARS-CoV-2 in vitro, we tested hydroxychloroquine as a treatment in Covid-19 patients [XREF_BIBR, XREF_BIBR]."
reach
"Initial studies found both chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) inhibits SARS-CoV-2 effectively in vitro [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
reach
"There are in vitro studies that show both chloroquine and hydroxychloroquine inhibit SARS-CoV-2 in vitro, although hydroxychloroquine appears to be more potent [45]."
reach
"Three studies have demonstrated that chloroquine phosphate inhibits SARS-CoV-2 [XREF_BIBR, XREF_BIBR, XREF_BIBR] and two have demonstrated that hydroxychloroquine sulfate inhibits SARS-CoV-2 [XREF_BIBR, XREF_BIBR] in vitro."
eidos
"These results are of great importance because a recent paper has shown that the mean duration of viral shedding in patients suffering from COVID-19 in China was 20 days ( even 37 days for the longest duration ) [ 19 ] Very recently , a Chinese team published results of a study demonstrating that chloroquine and hydroxychloroquine inhibit SARS-CoV-2 in vitro with hydroxychloroquine ( EC50 =0 .72 % muM ) found to be more potent than chloroquine ( EC50 = 5.47 % muM ) [ 14 ] ."
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"Also, chloroquine and hydroxychloroquine, have been reported to inhibit SARS-CoV-2 in vitro, although hydroxychloroquine appears to have more potent antiviral activity [XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR]."
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"Also, chloroquine and hydroxychloroquine, have been reported to inhibit SARS-CoV-2 in vitro, although hydroxychloroquine appears to have more potent antiviral activity [XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR]."
eidos
"These results are of great importance because a recent paper has shown that the mean duration of viral shedding in patients suffering from COVID - Very recently , a Chinese team published results of a study demonstrating that chloroquine and hydroxychloroquine inhibit SARS-CoV-2 in vitro with hydroxychloroquine ( EC50 =0 .72 % muM ) found to be more potent than chloroquine ( EC50 = 5.47 % muM ) [ 14 ] ."
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"A Chinese team published results of a study demonstrating that chloroquine, an antimalarial, and its hydroxyl analogue, hydroxychloroquine, inhibit SARS-CoV-2 in vitro with hydroxychloroquine (EC50 = 0.72% muM) found to be more potent than chloroquine (EC50 = 5.47% muM) [XREF_BIBR]."
| 9
| 5
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"Indeed, in patients with SLE, hydroxychloroquine reduces disease activity, CV risk, insulin resistance and thromboembolic events; therefore, in the perioperative period, it should not be discontinued and could even be protective [XREF_BIBR - XREF_BIBR]."
reach
"Hydroxychloroquine in lupus patients, reduces disease activity, cardiovascular risk, insulin resistance, thromboembolic events, infection risk and mortality XREF_BIBR - XREF_BIBR, and this drug should not be discontinued during the perioperative period."
reach
"Hydroxychloroquine has been reported to reduce insulin requirements in refractory type II diabetes by an average of 30%."
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"Hydroxychloroquine was found to significantly reduce insulin metabolism in the cytosolic fraction of livers of both healthy and diabetic animals."
reach
"Hydroxychloroquine may be able to partially reduce the post-receptor increased insulin clearance, accelerating insulin stimulated glucose transport which leads to better management of the disease."
Hydroxychloroquine activates INS.
| 3
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"Hydroxychloroquine (HCQ) has been found to significantly increase the insulin sensitivity index (ISI) and show a tendency to reduce IR (as assessed by the homeostatic model assessment for insulin resistance [HOMA-IR]) [XREF_BIBR]."
reach
"Hydroxychloroquine prevents insulin degradation in the liver and suppresses gluconeogenesis, increasing peripheral utilization of glucose; so, it is particularly attractive to use in patients also treated with corticosteroids."
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"Patients with SLE taking an antimalarial agent have also been shown to have lower fasting blood glucose conentrations - a risk factor for premature atherosclerosis - compared with controls [XREF_BIBR], and one study demonstrated that hydroxychloroquine prolongs the half-life of the active insulin and receptor complex via inhibition of the insulin-receptor dissociation, thus augmenting insulin stimulated responses [XREF_BIBR]."
Hydroxychloroquine increases the amount of INS.
| 1
Hydroxychloroquine increases the amount of INS. 1 / 1
| 1
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"The use of hydroxychloroquine may increase the serum insulin level in patients with prediabetic states who are at risk of developing diabetes mellitus."
| 8
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"A role of TLRs in HIV induced immune activation is also supported by the reduction in immune activation by TLR7 and TLR9 signaling inhibitors such as chloroquine and hydroxychloroquine [XREF_BIBR, XREF_BIBR]."
reach
"In rheumatoid arthritis and systemic lupus erythematosus, hydroxychloroquine has been suggested to mediate its anti-inflammatory action by inhibiting the activation of TLR7 and TLR9 that reside in endosomal/lysosomal compartments 23."
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"The TLR7 to TLR9 blocker hydroxychloroquine has been in use in patients with lupus for more than 50years, but oligonucleotide based inhibitors of TLR7 to TLR9, despite showing promise in animal models of lupus, have not reached the primary end point in a recent phase 1 trial."
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"Given that the endosomal maturation inhibitor hydroxychloroquine inhibits TLR9 activation and is a common treatment for SjS XREF_BIBR, we injected NOD and BALB/c mice with ODN2088, which dramatically increased salivation in NOD mice (p = 0.0018) (XREF_FIG)."
reach
"On the contrary, Yu et al., have hypothesized that hydroxychloroquine and other antimalarials, by inhibiting the toll like receptor-9 (TLR9), may induce persistence of HPV in lupus erythematosus patients."
reach
"Taken together, hydroxychloroquine markedly suppresses the TLR9 mediated human B cell functions during inflammatory processes."
reach
"Other Toll like targets are of interest as well, such as TLR-7 and TLR-9 blockage by hydroxychloroquine, which has been used successfully in inflammatory disorders such as systemic lupus erythematosus [XREF_BIBR] and post-Lyme 's arthritis [XREF_BIBR]."
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"Hydroxychloroquine is a potent inhibitor of TLR-9, and to a lesser extent TLR-7 and TLR-8, and inhibits antigen processing and presentation via alkalinization of proteasomes [XREF_BIBR, XREF_BIBR]."
1 | 7
| 4
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"This was also seen after removal of patients prescribed the glucocorticoid prednisone, which has been reported to inhibit NF-kappaB activation, and hydroxychloroquine (Plaquenil (R)) inhibiting TLR7 and -9 signaling."
reach
"Other Toll like targets are of interest as well, such as TLR-7 and TLR-9 blockage by hydroxychloroquine, which has been used successfully in inflammatory disorders such as systemic lupus erythematosus [XREF_BIBR] and post-Lyme 's arthritis [XREF_BIBR]."
reach
"A role of TLRs in HIV induced immune activation is also supported by the reduction in immune activation by TLR7 and TLR9 signaling inhibitors such as chloroquine and hydroxychloroquine [XREF_BIBR, XREF_BIBR]."
reach
"In rheumatoid arthritis and systemic lupus erythematosus, hydroxychloroquine has been suggested to mediate its anti-inflammatory action by inhibiting the activation of TLR7 and TLR9 that reside in endosomal/lysosomal compartments 23."
Hydroxychloroquine decreases the amount of TLR7.
1 | 3
Hydroxychloroquine decreases the amount of TLR7. 4 / 4
1 | 3
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"In conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate expression levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response to HPV infection."
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"In conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate protein levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response against HPV infection."
reach
"Our findings showed that prednisolone and hydroxychloroquine may down-regulate levels of TLR7 and TLR9, respectively."
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| 5
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"During follow-up, 58% were treated with methotrexate, 60% were treated with hydroxychloroquine, 32% of patients were treated with other DMARDs and 17% of patients were treated with biologic response modifiers, of which the vast majority (95%) received anti-TNFalpha therapy."
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"Hydroxychloroquine is known to increase the potency of methotrexate as well as increase its safety profile and reduce the dose."
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"[XREF_BIBR] Another study has concluded that hydroxychloroquine increased the potency of methotrexate and also sustained its effect."
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"A combination of hydroxychloroquine with methotrexate appears to reduce significantly the hepatic toxicity of methotrexate."
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"Hydroxychloroquine does not decrease serum methotrexate concentrations in children with juvenile idiopathic arthritis."
| 5
Hydroxychloroquine decreases the amount of glucose.
| 3
Hydroxychloroquine decreases the amount of glucose. 3 / 3
| 3
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"Anti-malarial agents, like chloroquine and hydroxychloroquine have anti-inflammatory effects and they are also effective in sarcoidosis, especially in patients with NS and sarcoidosis induced hypercalcemia and/or sarcoid skin lesions; its standard oral dosage is 250-750mg daily; hydroxychloroquine has lower risk of ocular toxicity than chloroquine, but is less effective than chloroquine; because hydroxychloroquine reduces serum glucose levels, it may be useful for NS patients with steroid induced hyperglycemia; its standard dosage is 200-400mg daily orally [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"This clinical interventional study demonstrated that 12 weeks of hydroxychloroquine treatment reduced the serum glucose levels of the patients studies."
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"[XREF_BIBR XREF_BIBR] In conclusion, hydroxychloroquine can effectively lower glucose levels through increase insulin level."
| 2
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"The group receiving hydroxychloroquine experienced reduction of glucose at 60 min of Oral Glucose Tolerance Test (OGTT) test after intervention, while the placebo group experienced increase of blood glucose at the same time."
reach
"Also, regarding changes in serum glucose concentration, there were no significant differences in the changes of blood glucose level after intervention in each group [XREF_FIG]; however, the group of patients receiving hydroxychloroquine experienced reduction of glucose at 60 min of OGTT test after intervention, while the placebo group experienced increase of blood glucose at the same time (from 163.0 +/- 39.4 to 158.4 +/- 36.3 mg/dL in the case group and from 163.3 +/- 39.2 to 181.7 +/- 51.7 mg/dL in the control group, P = 0.033)."
| 5
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"On the other hand, hydroxychloroquine has been reported to decrease total and LDL cholesterol and triglyceride concentrations [XREF_BIBR]."
reach
"Also important to its anti-atherosclerotic potential, hydroxychloroquine treatment has been shown to reduce total serum cholesterol [XREF_BIBR - XREF_BIBR]."
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"However, hydroxychloroquine, one of two tested s-Et 3 N drugs at a cytostatic concentration (50 muM), increased total and free cholesterol over 48 h; procainamide (2.5 mM) was inactive in this respect (Suppl."
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"Improvement of serum cholesterol in patients treated with hydroxychloroquine has been reported."
Hydroxychloroquine decreases the amount of cholesterol.
| 1
Hydroxychloroquine decreases the amount of cholesterol. 1 / 1
| 1
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"Hydroxychloroquine reduces low-density lipoprotein cholesterol levels in systemic lupus erythematosus : a longitudinal evaluation of the lipid lowering effect."
| 5
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"A 35-year-old male patient with a medical history of chronic hepatitis c virus (genotype 1a) since 1999 and rheumatoid arthritis (RA) treated with hydroxychloroquine was examined in the hepatology unit of our Hospital."
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"They demonstrated that CD4 + T cells from RA patients treated with hydroxychloroquine (HCQ) showed increased levels of LC3-II and autophagosomes number compared with cells isolated from healthy donors."
reach
"In Case 1, a 68-year-old Caucasian woman with a history of RA was initially treated with hydroxychloroquine."
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"As several studies suggested an association between hydroxychloroquine and lipid concentrations, Munro et al conducted a randomized one-year trial in patients with established RA where 100 patients were either treated with hydroxychloroquine (n = 51) or gold (n =."
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"The investigators concluded that addition of low-dose CsA was moderately effective in patients with early RA previously treated with low-dose hydroxychloroquine but with an unfavorable risk and benefit profile due to substantial renal function loss and gastrointestinal (GI) toxicity.In contrast, when all patients in our study were analyzed together there was evident improvement of measured clinical variables of efficacy at 6 and 12 months as compared with basal values."
| 5
Hydroxychloroquine deglycosylates ACE2.
| 3
Hydroxychloroquine leads to the deglycosylation of ACE2. 3 / 3
| 3
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"The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections."
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"The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections."
reach
"It has been posited that the antimalaric drugs chloroquine and hydroxychloroquine reduce glycosylation of ACE2, thus preventing SARS-CoV-2 from binding to host cells."
Hydroxychloroquine glycosylates ACE2.
| 2
Hydroxychloroquine leads to the glycosylation of ACE2. 2 / 2
| 2
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"The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections."
reach
"The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections."
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| 4
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"For immunosuppressors, 67.6% SLE-PAH patients were treated with cyclophosphamide, and 47.7% were treated with hydroxychloroquine."
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"Two antimalarial drugs, CLQ and hydroxychloroquine, inhibited the autophagy induced by p53 mediated apoptosis and augmented the anticancer activity of cyclophosphamide in Myc driven lymphoma [XREF_BIBR, XREF_BIBR]."
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"During follow-up, immunosuppressive management consisted of azathioprine in 54%, cyclophosphamide in 66.6%, mycophenolate mofetil in 31%, a combination of more than one of the above in 56.7%, being the most frequent azathioprine and cyclophosphamide; 22 individuals (14%) were only treated with hydroxychloroquine as an immunomodulator."
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"XREF_BIBR, XREF_BIBR Chloroquine and hydroxychloroquine can inhibit autophagy induced by p53 controlled apoptosis in Myc driven lymphoma and augmented the anticancer activity of cyclophosphamide."
| 2 2
| 2 1
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"A substantial reduction in viral load and more rapid virus elimination was seen in patients treated with a combination of hydroxychloroquine and azithromycin; however, the majority of patients treated with hydroxychloroquine alone continued to display symptoms of upper or lower respiratory tract infections [XREF_BIBR]."
eidos
"A French paper reporting on the use of drug combinations in infected patients highlighted the possibility that hydroxychloroquine is effective in the treatment of COVID-19 patients [ 4 ] particularly in combination with azithromycin ."
reach
"He was continued on azithromycin and ceftriaxone and treated with hydroxychloroquine 400mg daily."
eidos
"In a small study , hydroxychloroquine significantly decreased viral load in COVID-19 patients and the addition of azithromycin further enhanced the reduction in viral load ."
| 4
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"Chloroquine and hydroxychloroquine accumulate within lysosomes and are thought to block autophagy by elevating intralysosomal pH and inhibiting lysosomal enzymes [XREF_BIBR, XREF_BIBR]."
reach
"Chloroquine (CQ) and its derivative hydroxychloroquine impair lysosomal function by altering lysosomal pH; these drugs thereby inhibit the lysosome dependent degradation of autophagosomes."
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"Hydroxychloroquine is thought to inhibit growth of C. burnetii in vivo by raising the pH of typically acidic intracellular compartments."
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"It is estimated that the virus binds ACE2 at acidic pH since hydroxychloroquine reduces the viral load by making pH elevation."
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"Hydroxychloroquine, a drug often used in the treatment of SLE with ability to reduce sensitivity of the skin to UV exposure, can inhibit Th17 cell expansion and IL-17 production [XREF_BIBR]."
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"Furthermore, considering that the levels of systemic inflammation biomarkers significantly decreased among good responders in our study, it is notable that methotrexate alone or in combination with sulfasalazine reduces circulating levels of IL-6 [XREF_BIBR], and hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production from PBMC [XREF_BIBR]."
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"CONCLUSIONS Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication."
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"Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication."
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"Wahie S et al studied DLE patients treated with hydroxychloroquine and found that cigarette smoking did not have any significant influence on the response to this medication."
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"We conducted a multicenter observational and pharmacogenetic study of 200 patients with DLE treated with hydroxychloroquine."
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"10 years ago, he was diagnosed to have DLE and was treated with hydroxychloroquine and topical corticosteroids."
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"We report herein a generalized variant of canine DLE successfully treated with the antimalarial immunomodulator hydroxychloroquine (HCQ)."
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Hydroxychloroquine decreases the amount of TNF.
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Hydroxychloroquine decreases the amount of TNF. 3 / 3
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No evidence text available
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"In another single-arm study, administration of hydroxychloroquine to HIV infected persons who experienced suboptimal CD4 T-cell gains after highly active antiretroviral therapy (HAART) resulted in decreased levels of T-cell activation and decreased levels of inflammatory cytokines IL-6 and TNF in plasma."
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"Additionally, in a monocytic cell line, hydroxychloroquine attenuated TNF-alpha and IL6 expression in response to IL-1beta and TNF-alpha stimulation, respectively 46."
Hydroxychloroquine increases the amount of TNF.
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Hydroxychloroquine increases the amount of TNF. 1 / 1
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No evidence text available
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Hydroxychloroquine decreases the amount of TLR9. 4 / 4
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No evidence text available
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"In conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate protein levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response against HPV infection."
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"In conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate expression levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response to HPV infection."
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"Our findings showed that prednisolone and hydroxychloroquine may down-regulate levels of TLR7 and TLR9, respectively."
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"Forty-five (65.2%) of the patients received oral medication for SLE treatment during pregnancy, and 44 (63.8%) were treated with prednisone and 19 (27.5%) were treated with hydroxychloroquine."
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"In contrast, combined treatment with prednisone and either danazol (n = 18) or hydroxychloroquine (n = 11) resulted in 50% (7 CR, 2 PR) and 64% (4 CR, 3 PR) longterm responses, respectively, allowing prednisone to be withdrawn or the dose tapered below 0.2 mg/kg body weight and day."
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"Compared to MMF new users, CYC new users had higher SLE risk adjustment indices, less frequent hydroxychloroquine use, increased hospitalizations and higher cumulative median prednisone doses."
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"Rapamycin can inhibit the proliferation, induce apoptosis and autophagy of RPMI 8226, the hydroxychloroquine can inhibit autophagy and proliferation of RPMI 8226, and induce apoptosis, the 3-MA can inhibit autophagy of RPMI 8226, but hardly has any effects on proliferation and apoptosis of RPMI 8226 cells."
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"The patient 's cultured fibroblasts were incubated with selected drugs, and cell proliferation was inhibited by hydroxychloroquine."
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"It is not clear whether this is related to the fact that anti-malarial drugs, such as hydroxychloroquine, have been used as a secondary treatment for RA for many years 22, and it has been suggested that hydroxychloroquine interferes with Toll like receptor signaling 23 to reduce immune cell activation and proliferation, although its exact mechanism of action in ameliorating RA is still not well understood."
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"Additionally, chloroquine and hydroxychloroquine inhibit the Toll like receptor (TLR) pathway; the TLR pathway is involved in pro inflammatory cytokine signaling [XREF_BIBR]."
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"Hydroxychloroquine inhibits Toll like receptor pathways and minimizes flare, treats skin disease, and decreases the rate of autoantibody production [XREF_BIBR, XREF_BIBR,]."
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"Hydroxychloroquine, which inhibits Toll like receptor activation, has anecdotally been helpful as an adjunctive agent and has been shown to improve cutaneous and renal disease activity and prevent disease damage in lupus 107."
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eidos
"Hydroxychloroquine is known to block Kv11.1 ( HERG ) and can cause drug-induced long-QT syndrome [ 5 ] ."
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"Additionally, for hydroxychloroquine, a recent study pointed out that hydroxychloroquine could lead to unwanted QT interval prolongation by blocking the KCNH2 encoded hERG and Kv11.1 potassium channel, thereby increasing the risk of drug induced torsade de pointes and sudden cardiac death."
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"Finally, hydroxychloroquine blocks the KCNH2 encoded hERG and Kv11.1 potassium channel and can potentially prolong the corrected QT interval, with potentially severe consequences, such as sudden cardiac death and cardiac arrhythmia in patients with covid-19."
Hydroxychloroquine affects IgG
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Hydroxychloroquine activates IgG.
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"Patients with PAPS with medium-to-high anti-beta2GPI antibody titers of either IgG or IgM isotype had higher IFN scores, whereas those treated with hydroxychloroquine had lower scores, after adjusting for age and gender and other APS related factors."
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"Moreover, hydroxychloroquine has been reported to increase salivary flow rate by inhibiting glandular cholinesterase [XREF_BIBR], decrease inflammatory indices, that is, ESR and C reactive protein (CRP), and immunological abnormalities, that is, gamma-globulin, IgG, IgM, RF, anti-Ro, anti-La."
Hydroxychloroquine inhibits IgG.
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"XREF_BIBR Hydroxychloroquine, an effective and widely used therapy in SLE patients inhibits the DNA sensing TLR9 pathway and was demonstrated to inhibit IgG secretion by B cells stimulated with NET derived LL37-DNA complexes."
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"In support of this observation, administration of hydroxychloroquine -an inhibitor of IFNalpha production by PDCs through alterations of endodomal function- is beneficial in the management of musculoskeletal complaints in the setting of both lupus and SS [XREF_BIBR] [XREF_BIBR]."
Hydroxychloroquine decreases the amount of IFNA.
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Hydroxychloroquine decreases the amount of IFNA. 1 / 1
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"SIGLEC1 and IFN-alpha expression were reduced by hydroxychloroquine and oral glucocorticoids."
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"69 Taken together, the findings of these studies suggest that inhibition of IFN-alpha production by hydroxychloroquine or chloroquine has detrimental effects on the control of HIV or SIV replication but might suppress immune activation associated with increased IFN-alpha activity in HIV patients receiving ART that optimally suppresses HIV replication."
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"23 Hydroxychloroquine has also been found to reverse the effects of aPL on annexin A5 and coagulation on the surface of trophoblasts, and it prevents the effects of aPL on trophoblast migration, hCG secretion and fusion."
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"Hydroxychloroquine decreased aPL titers and lowered the odds of having persistently positive aPL in an observational study."
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"Hydroxychloroquine (HCQ) has been shown to decrease aPL titers in laboratory studies."
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"The chloroquine analogs amodiaquine (XREF_SUPPLEMENTARY) and hydroxychloroquine (XREF_SUPPLEMENTARY) significantly reduced cell viability in a concentration dependent manner similar to that of chloroquine, although amodiaquine was 2-3 times more potent in reducing cell viability by 50% (~ 15 muM) in comparison to chloroquine (~ 40 muM) and hydroxychloroquine (~ 50 muM)."
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"Chloroquine and its analog hydroxychloroquine, which block lysosome-autophagosome fusion and lysosomal function thus suppressing macroautophagy and chaperone mediated autophagy, can inhibit cancer cell survival under stress conditions 1."
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"Moreover, we found that autophagy plays a cytoprotective role by MTT analysis of the cell viability in TSCCs when treated with rapamycin or hydroxychloroquine (HCQ) in combination with erlotinib."
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"These results show that chloroquine and hydroxychloroquine specifically inhibit CXCR4 mediated signaling to suppress cell proliferation in pancreatic cancer cells."
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"The results of these assays show that chloroquine and hydroxychloroquine directly inhibit CXCR4 signaling."
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"11 More recently, the ability of CQ and its derivatives like hydroxychloroquine (HCQ) to inhibit CXCR4 has also been recognized and successfully utilized in the treatment of several types of solid tumors."
Hydroxychloroquine affects AGEP
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Hydroxychloroquine activates AGEP. 3 / 3
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"[XREF_BIBR] We report a case of AGEP induced by hydroxychloroquine with systemic involvement."
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"Hydroxychloroquine, which is used to treat some dermatologic and rheumatologic diseases because of its anti-inflammatory and immunosuppressive effects, is an uncommon cause of AGEP."
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"Hydroxychloroquine (HCQ) is an uncommon cause of AGEP with a prolonged recovery course; Thus, the physicians should take the possibility of this rare but severe event in their minds and try to diagnose correctly and better management."
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No evidence text available
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No evidence text available
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No evidence text available
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"It has been hypothesized that hydroxychloroquine could potentiate the activity of vorinostat through inhibition of autophagy, and this combination has been evaluated for safety in the oncology setting [XREF_BIBR]."
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"Hydroxychloroquine (HCQ) enhances the anti-cancer activity of the histone deacetylase inhibitor, vorinostat (VOR), in pre-clinical models and early phase clinical studies of metastatic colorectal cancer (mCRC)."
Hydroxychloroquine affects viral load COVID-19 patients
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Hydroxychloroquine inhibits viral load COVID-19 patients. 2 / 2
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eidos
"In a small study , hydroxychloroquine significantly decreased viral load in COVID-19 patients and the addition of azithromycin further enhanced the reduction in viral load ."
eidos
"Interestingly , hydroxychloroquine has also been found to be effective against SARS-CoV-2 in-vitro and in reducing viral load in COVID-19 patients ."
Hydroxychloroquine affects viral load
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Hydroxychloroquine inhibits viral load. 2 / 2
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eidos
"In a small study , hydroxychloroquine significantly decreased viral load in COVID-19 patients and the addition of azithromycin further enhanced the reduction in viral load ."