The binding and subsequent inhibition of tubulin polymerization in Ascaris suum (in vitro) by benzimidazole anthelmintics

Barrowman, Margaret M.; Marriner, S. E.; Bogan, J. A.

doi:10.1016/0006-2952(84)90605-1

Cited by 51 publications

(20 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequent studies confirmed this observation in other BZ-sensitive species of helminths [12]. It has been shown that these compounds inhibit tubulin polymerization by competing for the colchicine-binding site on tubulin [13, 14, 15]. In addition to their involvement in a number of cellular functions, microtubules also play a key role in the formation of the mitotic spindles, disruption of which would consequently lead to cell death [16].…”

Section: Discussionsupporting

confidence: 50%

Pilot Study of Albendazole in Patients with Advanced Malignancy

Morris

Jourdan

Pourgholami³

2001

Oncology

View full text Add to dashboard Cite

Our preclinical studies have shown that the widely used antiparasitic drug albendazole has potent antiproliferative activity against colorectal cancer (CRC) and hepatocellular carcinoma (HCC). This trial was designed to evaluate albendazole in a small number of patients (n = 7) with either HCC or CRC and hepatic metastases refractory to other forms of therapy. Albendazole was given at 10 mg/kg/day orally in two divided doses for a period of 28 days. To follow the effect of treatment, tumor markers, carcinoembryonic antigen (CEA) or α-feto protein (AFP), were measured routinely in these patients. A range of hematological and biochemical indices were also serially measured to monitor bone marrow, kidney or liver toxicity. Albendazole therapy resulted in a decrease in CEA in 2 patients. In the remaining 5 with measurable tumor markers, serum CEA or AFP was stabilized in 3 patients, while in the other 2, after an initial stabilization (5–10 days), the markers began to increase. In the 7 patients completing the trial, albendazole was well tolerated and there were no significant changes in any hematological, kidney or liver function tests, but 3 patients were withdrawn for severe neutropenia which was probably contributory to the death of 1 patient. These data support our previous experimental results demonstrating that albendazole has antitumor effects.

show abstract

Section: Discussionsupporting

confidence: 50%

Pilot Study of Albendazole in Patients with Advanced Malignancy

Morris

Jourdan

Pourgholami³

2001

Oncology

View full text Add to dashboard Cite

show abstract

“…Albendazole is poorly absorbed from the gastrointestinal tract (although it is absorbed better than mebendazole) and is rapidly converted in the liver to its active primary metabolite, albendazole sulfoxide, prior to reaching the systemic circulation. Oral bioavailability appears to be enhanced when albendazole is coadministered with a fatty meal (2). The drug has been found to be safe and relatively well tolerated, with the main side effects being nausea, dizziness, headache, and occasionally abnormal liver function tests and a transient leukopenia.…”

Section: Treatmentmentioning

confidence: 99%

Gnathostomiasis, Another Emerging Imported Disease

2009

View full text Add to dashboard Cite

SUMMARY Gnathostomiasis is a food-borne zoonosis caused by the late-third stage larvae of Gnathostoma spp. It is being seen with increasing frequency in countries where it is not endemic and should be regarded as another emerging imported disease. Previously, its foci of endemicity have been confined to Southeast Asia and Central and South America, but its geographical boundaries appear to be increasing, with recent reports of infection in tourists returning from southern Africa. It has a complex life cycle involving at least two intermediate hosts, with humans being accidental hosts in which the larvae cannot reach sexual maturity. The main risks for acquisition are consumption of raw or undercooked freshwater fish and geographical exposure. Infection results in initial nonspecific symptoms followed by cutaneous and/or visceral larva migrans, with the latter carrying high morbidity and mortality rates if there is central nervous system involvement. We review the literature and describe the epidemiology, life cycle, clinical features, diagnosis, treatment, and prevention of gnathostomiasis.

show abstract

“…As an oral anthelmintic, its efficacy and safety has been well established (11). The primary mode of action of albendazole in susceptible parasites has been described as binding to htubulin and leading to inhibition of microtubule polymerization (12,13). Our interest in benzimidazole carbamates dates back to the 1980s when the drug was tested for hydatid disease (14).…”

mentioning

confidence: 99%

Albendazole: a Potent Inhibitor of Vascular Endothelial Growth Factor and Malignant Ascites Formation in OVCAR-3 Tumor-Bearing Nude Mice

Pourgholami

Cai

et al. 2006

Clinical Cancer Research

134

View full text Add to dashboard Cite

Purpose: Angiogenesis and vessel hyperpermeability are the two factors leading to the formation of ascites. Vascular endothelial growth factor (VEGF) plays a pivotal role in malignant ascites formation.We have recently shown that albendazole inhibits peritoneal growth of human colorectal cancer cells . The present study was designed to find out if albendazole can suppress ascites formation in ascites-producing peritoneal carcinomatosis. Experimental design: Female nude mice bearing peritoneal tumors of human ovarian cancer cells (OVCAR-3) were treated with albendazole. Following i.p. inoculation and ascites development, mice were given i.p. albendazole (150 mg/kg) or the vehicle Â 3 weekly for 4 weeks. Results: Whereas vehicle-treated mice developed overt ascites requiring repeated aspiration, ascites formation in the albendazole-treated mice was markedly suppressed. As a result of this, 7 of 10 mice from the control group had to be euthanized before the course of treatment was over. Suppressed ascites production and reduced tumor vascularity observed was a result of dramatic reduction in tumor VEGF production as revealed by profoundly lower VEGF ascites fluid and plasma levels. In vitro, incubation of SKOV-3 cells with various concentrations of albendazole led to significant dose-dependent inhibition of VEGF secretion. Examination of floating tumor cells collected from the peritoneal wash revealed profound down-regulation of VEGF mRNA in albendazole-treated mice. Conclusions: These findings suggest for the first time that in nude mice bearing OVCAR-3 peritoneal tumors, by inhibiting VEGF production, albendazole abolishes tumor angiogenesis and ascites formation.The formation of malignant ascites in patients with advancedstage cancer is a difficult problem to manage in clinical oncology (1). It is an important cause of morbidity and mortality in patients with peritoneal carcinomatosis arising from colorectal, gastric, pancreatic, endometrial, and ovarian cancers (2). Ovarian carcinoma is characterized by rapid growth of solid i.p. tumors and production of large volumes of ascites. Although malignant progression of this disease is often predominantly confined to the peritoneal cavity (3), two thirds of patients already have advanced disease when diagnosed, and rapidly accumulating ascitic fluid is associated with poor prognosis (4). Both tumor size and the accumulation of ascites are inversely associated with survival (5). Among women with stage III or IV epithelial ovarian carcinoma, development of ascites correlates with a significantly decreased 5-year survival rate (5% with ascites versus 45% without ascites; ref. 6). Despite advances in surgical cytoreduction and cytotoxic chemotherapy, the prognosis for patients with ovarian cancer remains poor (7). Current therapeutic treatment of patients with advanced ovarian cancer associates cytoreductive surgery and chemotherapy, the combination of paclitaxel and a platinum salt being considered as the standard chemotherapy for advanced ovarian cancer (8).Dur...

show abstract

The binding and subsequent inhibition of tubulin polymerization in Ascaris suum (in vitro) by benzimidazole anthelmintics

Cited by 51 publications

References 7 publications

Pilot Study of Albendazole in Patients with Advanced Malignancy

Pilot Study of Albendazole in Patients with Advanced Malignancy

Gnathostomiasis, Another Emerging Imported Disease

Albendazole: a Potent Inhibitor of Vascular Endothelial Growth Factor and Malignant Ascites Formation in OVCAR-3 Tumor-Bearing Nude Mice

Contact Info

Product

Resources

About