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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 -
Deutsches Arzteblatt International Mar 2019Symptomatic infection with pinworm (Enterobius vermicularis), a human pathogen, is clinically relevant in Germany, with an estimated prevalence in childhood of 2-20%....
BACKGROUND
Symptomatic infection with pinworm (Enterobius vermicularis), a human pathogen, is clinically relevant in Germany, with an estimated prevalence in childhood of 2-20%. Enterobiasis can cause major mental distress. There is little systematically verified knowledge on the treatment of this condition, and there is no corresponding German guideline. This review is, therefore, intended as a summary of the current state of knowledge.
METHODS
This review is based on pertinent publications retrieved by a selective search in PubMed for literature appearing from 1 January 1990 to 5 February 2019 and containing the search terms "enterobiasis," "oxyuriasis," "Enterobius vermicula- ris," "pinworm," and "threadworm."
RESULTS
More than one billion people worldwide are thought to be infected with pinworm. Estimates of its prevalence among kindergarten and primary-school pupils in Europe are generally near 20%. Infants (<2 years of age), adolescents (>14 years of age), and adults are only sporadically affected. The main risk factors are age 4-11 years, uncontrolled anus-finger-mouth contact, nail-biting (onychophagia/peri- onychophagia), unsupervised body hygiene, and poor compliance with basic hand hygiene. No large-scale, randomized, controlled trials of treatment are available. The approved antihelminthic agents are mebendazole, pyrantel embonate, and pyrvinium embonate (success rates up to >90%). For recurrent infections, prolonged treatment for up to 16 weeks (a "pulse scheme") is recommended.
CONCLUSION
In nearly all cases, antihelminthic treatment along with attention to hygienic measures can successfully eradicate pinworm infection and prevent recurrence and autoinfection. The involvement of all persons living in the patient's house- hold, including sexual partners, is a prerequisite to the lasting success of treatment.
Topics: Adolescent; Animals; Child; Child, Preschool; Enterobiasis; Enterobius; Europe; Germany; Humans; Hygiene; Infant
PubMed: 31064642
DOI: 10.3238/arztebl.2019.0213 -
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 -
Research and Reports in Tropical... 2018Mansonellosis is a filarial disease caused by three species of filarial (nematode) parasites (, , and ) that use humans as their main definitive hosts. These parasites... (Review)
Review
Mansonellosis is a filarial disease caused by three species of filarial (nematode) parasites (, , and ) that use humans as their main definitive hosts. These parasites are transmitted from person to person by bloodsucking females from two families of flies (Diptera). Biting midges (Ceratopogonidae) transmit all three species of , but blackflies (Simuliidae) are also known to play a role in the transmission of in parts of Latin America. and are endemic in western, eastern, and central Africa, and is also present in the neotropical region from equatorial Brazil to the Caribbean coast. has a patchy distribution in Latin America and the Caribbean. Mansonellosis infections are thought to have little pathogenicity and to be almost always asymptomatic, but occasionally causing itching, joint pains, enlarged lymph glands, and vague abdominal symptoms. In Brazil, infections are also associated with corneal lesions. Diagnosis is usually performed by detecting microfilariae in peripheral blood or skin without any periodicity. There is no standard treatment at present for mansonellosis. The combination therapy of diethylcarbamazine plus mebendazole for microfilaremia is presently one of the most widely used, but the use of ivermectin has also been proven to be very effective against microfilariae. Recently, doxycycline has shown excellent efficacy and safety when used as an antimicrobial against endosymbiotic bacteria harbored by some strains of and . Diethylcarbamazine and ivermectin have been used effectively to treat infection. There are at present no estimates of the disease burden caused by mansonellosis, and thus its importance to many global health professionals and policy makers is presently limited to how it can interfere with diagnostic tools used in modern filarial disease control and elimination programs aimed at other species of filariae.
PubMed: 30050351
DOI: 10.2147/RRTM.S125750