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The Korean Journal of Parasitology Jun 2021The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed.... (Review)
Review
The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.
Topics: Albendazole; Animals; Anthelmintics; Antineoplastic Agents; Ascariasis; Female; Humans; Male; Mebendazole; Parasites; Trichuriasis
PubMed: 34218593
DOI: 10.3347/kjp.2021.59.3.189 -
Nature Reviews. Disease Primers May 2020Trichuriasis and ascariasis are neglected tropical diseases caused by the gastrointestinal dwelling nematodes Trichuris trichiura (a whipworm) and Ascaris lumbricoides... (Review)
Review
Trichuriasis and ascariasis are neglected tropical diseases caused by the gastrointestinal dwelling nematodes Trichuris trichiura (a whipworm) and Ascaris lumbricoides (a roundworm), respectively. Both parasites are staggeringly prevalent, particularly in tropical and subtropical areas, and are associated with substantial morbidity. Infection is initiated by ingestion of infective eggs, which hatch in the intestine. Thereafter, T. trichiura larvae moult within intestinal epithelial cells, with adult worms embedded in a partially intracellular niche in the large intestine, whereas A. lumbricoides larvae penetrate the gut mucosa and migrate through the liver and lungs before returning to the lumen of the small intestine, where adult worms dwell. Both species elicit type 2 anti-parasite immunity. Diagnosis is typically based on clinical presentation (gastrointestinal symptoms and inflammation) and the detection of eggs or parasite DNA in the faeces. Prevention and treatment strategies rely on periodic mass drug administration (generally with albendazole or mebendazole) to at-risk populations and improvements in water, sanitation and hygiene. The effectiveness of drug treatment is very high for A. lumbricoides infections, whereas cure rates for T. trichiura infections are low. Novel anthelminthic drugs are needed, together with vaccine development and tools for diagnosis and assessment of parasite control in the field.
Topics: Animals; Ascariasis; Ascaris lumbricoides; Humans; Prevalence; Trichuriasis; Trichuris
PubMed: 32467581
DOI: 10.1038/s41572-020-0171-3 -
Recent Patents on Inflammation &... 2020Ascaris lumbricoides is the most common helminthic infection. More than 1.2 billion people have ascariasis worldwide. (Review)
Review
BACKGROUND
Ascaris lumbricoides is the most common helminthic infection. More than 1.2 billion people have ascariasis worldwide.
OBJECTIVE
This article aimed to provide an update on the evaluation, diagnosis, and treatment of ascariasis.
METHODS
A PubMed search was conducted in February 2020 in Clinical Queries using the key terms "ascariasis" OR "Ascaris lumbricoides". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 10 years. The search was restricted to English literature. The information retrieved from the above search was used in the compilation of the present article. Patents were searched using the key term "ascariasis" OR "Ascaris lumbricoides" in www.freepatentsonline.com.
RESULTS
Ascaris lumbricoides is transmitted through the ingestion of embryonated eggs from fecal- contaminated material. Ascariasis has high endemicity in tropical and subtropical areas. Predisposing factors include poverty, poor sanitation, inadequate sewage disposal, and poor personal hygiene. The prevalence is greatest in children younger than 5 years of age. The majority of patients with intestinal ascariasis are asymptomatic. For those with symptoms, anorexia, nausea, bloating, abdominal discomfort, recurrent abdominal pain, abdominal distension, and intermittent diarrhea are not uncommon. Other clinical manifestations vary widely, depending on the underlying complications. Complications include Löeffler syndrome, intestinal obstruction, biliary colic, recurrent pyogenic cholangitis, cholecystitis, acalculous cholecystitis, obstructive jaundice, cholelithiasis, pancreatitis, and malnutrition. The diagnosis is best established by microscopic examination of fecal smears or following concentration techniques for the characteristic ova. Patients with A. lumbricoides infection warrant anthelminthic treatment, even if they are asymptomatic, to prevent complications from migration of the parasite. Albendazole and mebendazole are the drugs of choice for children and nonpregnant individuals with ascariasis. Pregnant women with ascariasis should be treated with pyrantel pamoate. Recent patents related to the management of ascariasis are also discussed.
CONCLUSION
The average cure rate with anthelminthic treatment is over 95%. Unfortunately, most treated patients in endemic areas become re-infected within months. Health education, personal hygiene, improved sanitary conditions, proper disposal of human excreta, and discontinuing the use of human fecal matter as a fertilizer are effective long-term preventive measures. Targeting deworming treatment and mass anthelminthic treatment should be considered in regions where A. lumbricoides is prevalent.
Topics: Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Humans; Patents as Topic
PubMed: 32628606
DOI: 10.2174/1872213X14666200705235757 -
International Journal of Molecular... Jan 2023Repurposing approved non-antitumor drugs is a promising and affordable strategy in drug discovery to identify new therapeutic uses different from the original medical... (Review)
Review
Repurposing approved non-antitumor drugs is a promising and affordable strategy in drug discovery to identify new therapeutic uses different from the original medical indication that may help increase the number of possible, effective anticancer drugs. The use of drugs in ways other than their original FDA-approved indications could offer novel avenues such as bypassing the chemoresistance and recurrence seen with conventional therapy and treatment; moreover, it can offer a safe and economic strategy for combination therapy. Recent works have demonstrated the anticancer properties of the FDA-approved drug Mebendazole. This synthetic benzimidazole proved effective against a broad spectrum of intestinal Helminthiasis. Mebendazole can penetrate the blood-brain barrier and has been shown to inhibit the malignant progression of glioma by targeting signaling pathways related to cell proliferation, apoptosis, or invasion/migration, or by increasing the sensitivity of glioma cells to conventional chemotherapy or radiotherapy. Moreover, several preclinical models and ongoing clinical trials explore the efficacy of Mebendazole in multiple cancers, including acute myeloid leukemia, brain cancer, oropharyngeal squamous cell carcinoma, breast cancer, gastrointestinal cancer, lung carcinoma, adrenocortical carcinoma, prostate cancer, and head and neck cancer. The present review summarizes central literature regarding the anticancer effects of MBZ in cancer cell lines, animal tumor models, and clinical trials to suggest possible strategies for safe and economical combinations of anticancer therapies in brain cancer. Mebendazole might be an excellent candidate for the treatment of brain tumors because of its efficacy both when used as monotherapy and in combination as an enhancement to standard chemotherapeutics and radiotherapy, due to its effectiveness on tumor angiogenesis inhibition, cell cycle arrest, apoptosis induction, and targeting of critical pathways involved in cancer such as Hedgehog signaling. Therefore, attention to MBZ repurposing has recently increased because of its potential therapeutic versatility and significant clinical implications, such as reducing medical care costs and optimizing existing therapies. Using new treatments is essential, particularly when current therapeutics for patients with brain cancer fail.
Topics: Male; Animals; Mebendazole; Antiparasitic Agents; Cell Line, Tumor; Hedgehog Proteins; Antineoplastic Agents; Brain Neoplasms; Head and Neck Neoplasms; Anti-Infective Agents; Glioma
PubMed: 36674870
DOI: 10.3390/ijms24021334 -
Acta Pharmacologica Sinica Jan 2022Glioblastoma multiforme (GBM) is the most malignant and lethal primary brain tumor in adults accounting for about 50% of all gliomas. The only treatment available for...
Glioblastoma multiforme (GBM) is the most malignant and lethal primary brain tumor in adults accounting for about 50% of all gliomas. The only treatment available for GBM is the drug temozolomide, which unfortunately has frequent drug resistance issue. By analyzing the hub genes of GBM via weighted gene co-expression network analysis (WGCNA) of the cancer genome atlas (TCGA) dataset, and using the connectivity map (CMAP) platform for drug repurposing, we found that multiple azole compounds had potential anti-GBM activity. When their anti-GBM activity was examined, however, only three benzimidazole compounds, i.e. flubendazole, mebendazole and fenbendazole, potently and dose-dependently inhibited proliferation of U87 and U251 cells with IC values below 0.26 μM. Benzimidazoles (0.125-0.5 μM) dose-dependently suppressed DNA synthesis, cell migration and invasion, and regulated the expression of key epithelial-mesenchymal transition (EMT) markers in U87 and U251 cells. Benzimidazoles treatment also dose-dependently induced the GBM cell cycle arrest at the G/M phase via the P53/P21/cyclin B1 pathway. Furthermore, the drugs triggered pyroptosis of GBM cells through the NF-κB/NLRP3/GSDMD pathway, and might also concurrently induced mitochondria-dependent apoptosis. In a nude mouse U87 cell xenograft model, administration of flubendazole (12.5, 25, and 50 mg · kg · d, i.p, for 3 weeks) dose-dependently suppressed the tumor growth without obvious adverse effects. Taken together, our results demonstrated that benzimidazoles might be promising candidates for the treatment of GBM.
Topics: Antineoplastic Agents; Apoptosis; Benzimidazoles; Cell Cycle Checkpoints; Cell Movement; Cell Proliferation; Central Nervous System Neoplasms; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Glioblastoma; Humans; Molecular Structure; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 34433903
DOI: 10.1038/s41401-021-00752-y -
Immunity Apr 2022The epithelium is an integral component of mucosal barrier and host immunity. Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines,...
The epithelium is an integral component of mucosal barrier and host immunity. Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases.
Topics: Acylation; Alarmins; Anthelmintics; Biomarkers, Tumor; Cytokines; DNA-Binding Proteins; Helminthiasis; Humans; Hyperplasia; Inflammation; Interleukin-33; Intestinal Mucosa; Mebendazole; N-Acetylglucosaminyltransferases; Pore Forming Cytotoxic Proteins; STAT6 Transcription Factor
PubMed: 35385697
DOI: 10.1016/j.immuni.2022.03.009