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Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma.

Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumo

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… Inhibition of autophagy with chloroquine (CQ) inhibited the growth of these cells and accumulated LC3-II, indicative of an active autophagy directly involved in tumor progression [ 85 ]. … A search for phase II and III trials was operated on clinicaltrial.gov (data of entry 2020-01-15) combining terms such as cholangiocarcinoma, autophagy, mTOR, AKT, PI3K, chloroquine and hydroxychloroquine and obtaining a limited set of studies. …

Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.

Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, a

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… In fact, Chloroquine (CQ) and Hydroxychloroquine (HCQ), known autophagy inhibitors, are extensively used in clinical trials that target CSCs [ 215 ]. In gastrointestinal stromal tumors, a combination of imatinib and chloroquine (CQ) promotes tumor cell apoptosis [ 216 ]. … Hydroxychloroquine (HCQ), a chloroquine analog with one-third the toxicity, differs from chloroquine by the addition of a hydroxyl group and also inhibits autophagy [ 225 ]. …

Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgen

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… Hydroxychloroquine and Chloroquine Hydroxychloroquine and chloroquine are 4-aminoquinoline compounds. … Chloroquine has also been tested in a phase I trial ( NCT01777477 ) to evaluate its safety and preliminary efficacy when combined with gemcitabine [ 177 ]. …

Protecting Frontline Health Care Workers from COVID-19 with Hydroxychloroquine Pre-exposure Prophylaxis: A structured summary of a study protocol for a randomised placebo-controlled multisite trial in Toronto, Canada.

OBJECTIVES: Primary Objective: To determine if pre-exposure prophylaxis (PrEP) with 400mg hydroxychloroquine (HCQ), taken orally once daily reduces microbiologically confirmed COVID-19 among front line health care workers at high risk for SARS-CoV-2 exposure. Secondary Objectives: To compare the following between study arms: adverse events; symptomatic COVID-19; duration of symptomatic COVID-19; days hospitalized attributed to COVID-19; respiratory failure attributable to COVID-19 requiring i) non-invasive ventilation or ii) intubation/mechanical ventilation; mortality attributed to COVID-19, …

Hydroxychloroquine plus personal protective equipment versus standard personal protective equipment alone for the prevention of COVID-19 infections among frontline healthcare workers: the HydrOxychloroquine Prophylaxis Evaluation(HOPE) trial: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: To evaluate the effect of the combination of hydroxychloroquine (HCQ) and standard personal protective equipment (PPE) compared to the use of standard personal protective equipment alone on the proportion of laboratory confirmed COVID-19 infections among frontline healthcare workers(HCWs) in India TRIAL DESIGN: HOPE is an investigator initiated multi-centre open-label parallel group randomized controlled trial. PARTICIPANTS: All HCWs currently working in an environment with direct exposure to patients with confirmed COVID-19 infection are eligible to participate in the trial. The …

Malaria Surveillance - United States, 2013.

PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the … associated with pyrimethamine drug resistance, 74 (76%) with sulfadoxine resistance, 53 (53%) with chloroquine resistance, one (1%) with atovaquone resistance, none with mefloquine drug resistance, and none with artemisinin resistance. INTERPRETATION: The overall trend of malaria cases has been increasing since 1973; the number of cases reported in 2013 is …

Storage diseases with hypertrophic cardiomyopathy phenotype.

Never judge a book by its cover, nor assume hypertrophic cardiomyopathy (HCM) as sarcomeric, as appearances can deceive. HCM phenocopies account for a 5-10% of the cases, mainly represented by storage diseases, flagged by the increasing prevalence of senile cardiac amyloid in developing countries. Multisystemic and heterogeneous presentation of these entities is a challenge for clinicians, and time delay in diagnosis is a major concern. Promising drugs and gene-specific tailored therapies are under development, therefore, more than ever, appropriate understanding of these conditions is mandato

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… Amiodarone, chloroquine or indomethacin can also cause CV. CV can be present in females as a milder form. Another site of deposits is the posterior capsule, causing the Fabry cataract. … Interestingly, it is also under research the effect of the novel sodium/glucose cotransporter 1 (SGLT) inhibitors used for diabetes mellitus treatment 104 , as AMPK is a modulator for the SGLT activity. 2.5 Chloroquine-induced cardiomyopathy Extended therapies with chloroquine, an antimalarial drug …

Prospects for repurposing CNS drugs for cancer treatment.

Drug repurposing is the idea of using an already approved drug for another disease or disorder away from its initial use. This new approach ensures the reduction in high cost required for developing a new drug in addition to the time consumed, especially in the tumor disorders that show an unceasing rising rate with an unmet success rate of new anticancer drugs. In our review, we will review the anti-cancer effect of some CNS drugs, including both therapeutic and preventive, by searching the literature for preclinical or clinical evidence for anticancer potential of central nervous system drug

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… has been initiated in 2014 to highlight promising drug candidates with good toxicity profile and experimental evidence, to be subjected to clinical trials to validate their off-label usage. 4 The project has provided a list of candidate drugs, including Losartan, Omeprazole, Statins, Nitroglycerin, Chloroquine … Verbaanderd C Maes H Schaaf MB Sukhatme VP Pantziarka P Sukhatme V Repurposing drugs in oncology (ReDO) - Chloroquine and hydroxychloroquine as anti-cancer agents . Ecancermedicalscience . 2017 ; 11 : 781 . 29225688 10.3332/ecancer.2017.781 PMC5718030 7. …

IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives.

Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer.

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… Particularly great attention was dedicated to antimalarials, namely chloroquine and hydroxychloroquine. Based on the recently available Cochrane database analysis, the outcomes of this treatment are controversial [ 141 ]. … Chloroquine Treatment Influences Proinflammatory Cytokine Levels in Systemic Lupus Erythematosus Patients Lupus 2006 15 268 275 10.1191/0961203306lu2299oa 16761500 143. Van den Borne B.E. Dijkmans B.A. de Rooij H.H. le Cessie S. Verweij C.L. …

Primed for global coronavirus pandemic: Emerging research and clinical outcome.

The global effort to combat and contain the coronavirus disease 2019 (COVID-19) caused by the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now proceeding on a war footing. The world was slow to react to the developing crisis, but once the contours of the impending calamity became evident, the different state and non-state actors have raced to put their act together. The COVID-19 pandemic has blatantly exposed the shortcomings of our healthcare system and the limitations of medical science, despite considerable advances in recent years. To effectively tack

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… Medical Sciences, Iran | Phase-III IRCT20200128046294N2 (ICTPR) | RNA polymerase inhibitor 24 | Remdesivir (GS - 5734) (28) | Gilead Sciences,USA | >10 Clinical studies worldwide and included in WHO SOLIDARITY Trial NCT04323761 , NCT04257656 NCT04315948 ( ClinicalTrials.gov ) | RNA polymerase 25 | Chloroquine … Fig. 7 Reports suggest that antimalarial drugs, chloroquine (CQ) and hydroxychloroquine (HCQ) initially exhibited appreciable efficacy against COVID-19, possibly by interfering with ACE2 glycosylation and blocking endosomes acidification [ [62] , [63] , [64] , [65] ]. …

Drug Repurposing for Cancer Treatment: A Comprehensive Review.

Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million. In Saudi Arabia, there were 13,399 deaths caused by cancer and 28,113 newly diagnosed cases of cancer. Drug repurposing is a drug discovery strategy that has gained special attention and implementation to enhance the process of drug development due to its time- and money-saving effect. It involves repositioning existing medications to new clinical applications. Cancer treatment is a therap

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… Repurposing Anti-Helminthic Medication for Cancer Treatment Anti-parasitic medications, such as chloroquine and ivermectin, as well as mebendazole, flubendazole, and albendazole, have shown potential as anticancer agents. … Repurposing Anti-Malarial Medications for Cancer Treatment Chloroquine, artesunate, and mefloquine, originally developed to treat malaria, have shown efficacy against various diseases, including cancer. …

The CoV-2 outbreak: how hematologists could help to fight Covid-19.

COVID-19 is a medical emergency, with 20 % of patients presenting with severe clinical manifestations. From the pathogenetic point of view, COVID-19 mimics two other well-known diseases characterized by cytokine storm and hyper-activation of the immune response, with consequent organ damage: acute graft-versus-host disease (aGVHD) and macrophage activation syndrome (MAS). Hematologists are confident with these situations requiring a prompt therapeutic approach for switching off the uncontrolled cytokine release; here, we discuss pros and cons of drugs that are already employed in hematology in

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… In the early stage of SARS-CoV2 infection, chloroquine, imatinib or begelomab might be useful for blocking the attack of the viral S protein to the CD26 virus receptors, for modifying the lysosome pH or for restoring the anti-microbial autophagy. … Among the drugs that can be used against COVID-19, in that study on cGVHD the cheapest resulted chloroquine (9181 US$), followed by Imatinib (43,965 US$), and Ruxolitinib (97,807 US$) [ 111 ]. …

Antidepressant Drug Sertraline against Human Cancer Cells.

The use of FDA-approved drugs for new indications represents a faster and more economical way to find novel therapeutic agents for cancer therapy, compared to the development of new drugs. Repurposing drugs is advantageous in a pharmacological context since these drugs already have extensive data related to their pharmacokinetics, facilitating their approval process for different diseases. Several studies have reported the promising anticancer effects of sertraline, both alone and combined, in different types of cancer cell lines. Here, we performed a literature review on the anticancer potent

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… For example, the antiparasitic drugs chloroquine and ivermectin have been proposed for the treatment of COVID-19 [ 12 , 13 , 14 , 15 ]. … Breakthrough: Chloroquine Phosphate Has Shown Apparent Efficacy in Treatment of COVID-19 Associated Pneumonia in Clinical Studies Biosci. Trends 2020 14 72 73 10.5582/bst.2020.01047 32074550 14. Touret F. de Lamballerie X. Of Chloroquine and COVID-19 Antivir. …

Indian Society of Hematology and Blood Transfusion (ISHBT) Consensus Document on Hematological Practice During COVID-19 Pandemic.

The SARS-CoV-2 (COVID-19) pandemic is a worldwide public health emergency with widespread impact on health care delivery. Unforeseen challenges have been noted during administration of usual haematology care in these unusual COVID-19 times. Medical services have been overstretched and frontline health workers have borne the brunt of COVID-19 pandemic. Movement restrictions during lockdown prevented large sections of population from accessing health care, blood banks from holding blood drives, and disrupted delivery of diagnostic hematology services. The disruption in hematology care due to COV

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… Chloroquine, hydroxy-chloroquine (HCQ) can increase cardiac toxicity of anthracycline [ 16 ]. Azithromycin, HCQ, Chloroquine can increase QTc along with TKI (Imatinib, Dasatinib), Inotuzumab. Lopinavir/Ritonavir may increase the vincristine and methotrexate toxicity. …

Management of multiple myeloma during COVID-19 pandemic.

At the end of 2019, a novel coronavirus was identified as the cause of pneumonia cases in Wuhan, a city in the Hubei Province of China. On January 30, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a public health emergency of international concern and, in March 2020, began to characterize it as a pandemic. The virus that causes COVID-19 is designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) In February 2020, the World Health Organization designated the disease COVID-19, which stands for coronavirus disease 2019.

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… An old anti-malarial, chloroquine phosphate, has been effective in inhibiting the exacerbation of pneumonia due to its anti-viral and anti-inflammatory activities [34] . … Yang, Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies . (1881-7823(Electronic)). 10.5582/bst.2020.01047 32074550 35 Zhang, X., et al., First case of COVID-19 in a patient with multiple myeloma successfully treated with …

Molecular Mechanism of Autophagy and Its Regulation by Cannabinoids in Cancer.

Autophagy is a "self-degradation" process whereby malfunctioned cytoplasmic constituents and protein aggregates are engulfed by a vesicle called the autophagosome, and subsequently degraded by the lysosome. Autophagy plays a crucial role in sustaining protein homeostasis and can be an alternative source of energy under detrimental circumstances. Studies have demonstrated a paradoxical function for autophagy in cancer, displaying both tumour suppressive and tumour promotive roles. In early phases of tumour development autophagy promotes cancer cell death. In later phases, autophagy enables canc

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… Reagents such as chloroquine (CQ) and bafilomycin, however, elevate lysosomal pH and obstruct autophagic protein degradation. … Chloroquine and hydroxychloroquine for cancer therapy. Mol. Cell Oncol. 2014;1:e29911. doi: 10.4161/mco.29911. 109. Lin Y.C., Lin J.F., Wen S.I., Yang S.C., Tsai T.F., Chen H.E., Chou K.Y., Hwang T.I. …

Weathering the Cytokine Storm in COVID-19: Therapeutic Implications.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. SUMMARY: The pathophysiology of COVID-19 is far from being completely understood, and the lack of

LAPTM proteins in neurological disorders - Autophagy-lysosome dysfunction and therapeutic targets: A review.

Lysosomal-associated protein transmembrane (LAPTM) family members-LAPTM4A, LAPTM4B, and LAPTM5-regulate lysosomal integrity, autophagy-lysosome flux, lipid homeostasis, and immune signaling, pathways increasingly implicated in neurological disease. This review synthesizes structure-function evidence for LAPTM proteins and examines how their dysregulation contributes to Alzheimer's and Parkinson's disease, ischemia-reperfusion injury, and gliomas. Based on a targeted narrative analysis of primary and translational studies, we highlight that LAPTM proteins influence lysosomal acidification and m

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… In vitro studies demonstrate that chloroquine and bafilomycin A1 effectively reverse the LAPTM4B-mediated displacement of V-ATPase in human embryonic kidney 293 cells (HEK293) and the human neuroblastoma cell line SH-SY5Y. … Moreover, cancer-derived inhibitors such as chloroquine analogs demonstrate promise in preclinical models of ALS [ 106 ]. …

Current status of potential therapeutic candidates for the COVID-19 crisis.

As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tent

Medicine manipulation: An alternative to mitigate therapeutic gaps in the Brazilian Unified Health System?

Despite the various initiatives carried out in Brazil and in the world, the challenge of offering essential medicines in adequate presentations remains, especially to the public affected by diseases considered neglected and the pediatric population, for whom the therapeutic options remain limited. The main objective of this study was to evaluate the production of manipulated medicines as a strategy to mitigate therapeutic and access gaps to essential medicines within the Brazilian public health system, called the Unified Health System (SUS). The evaluation, carried out between 2020 and 2021, i

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… indomethacin, valproic acid, iodides, amphetamines, ipecac, antidepressant agents, antimony, mercuric chloride, arsenic, morphine, atropine, methylene blue, opium, barbiturates, organophosphates, camphor, acetaminophen, carbamazepine, paraquat, chlordiazepoxide, parathion, chlorpheniramine, penicillin, chloroquine … solution | Leprosy treatment; Primary and secondary prophylaxis of Pneumocystis jirovecii pneumonia in co-infection with HIV (alternative regimen); Primary and secondary prophylaxis of Toxoplasma gondii, in co-infection with HIV (alternative regimen); Treatment of dermatitis herpetiformis. | Infantile Chloroquine …