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PostPosted: Thu Feb 02, 2017 12:44 pm 
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The veterinary benzimidazoles:

mebendazole (MBZ),

fenbendazole (FBZ)

albendazole (ABZ)] have been found to have significant anti-tumor properties.






Quote:
Mebendazole Elicits a Potent Antitumor Effect on Human Cancer
Cell Lines Both in Vitro and in Vivo

ABSTRACT

We have found that mebendazole (MZ), a derivative of benzimidazole, induces a dose- and time-dependent apoptotic response in human lung cancer cell lines. In this study, MZ arrested cells at the G 2-M phase before the onset of apoptosis, as detected by using fluorescence-activated cell sorter analysis. MZ treatment also resulted in mitochondrial cytochrome c release, followed by apoptotic cell death. Additionally, MZ appeared to be a potent inhibitor of tumor cell growth with little toxicity to normal WI38 and human umbilical vein endothelial cells. When administered p.o. to nu/nu mice, MZ strongly inhibited the growth of human tumor xenografts and significantly reduced the number and size of tumors in an experimental model of lung metastasis. In assessing angiogenesis, we found significantly reduced vessel densities in MZ-treated mice compared with those in control mice. These results suggest that MZ is effective in the treatment of cancer and other angiogenesis-dependent diseases.


Hey! This is an easily purchased over-the-counter medication and may be worth a try in both man and animal!


Quote:
Human data in cancer

No clinical trials of MBZ as a cancer treatment have been completed to date. However, there are two well-documented case reports in the literature in favour of re-purposing MBZ as an anti-cancer therapy.

In 2011, a case of long-term tumour control in metastatic adrenocortical cancer was published [23]. Adrenocortical cancer is a relatively rare malignancy with few treatment options in the case of non-resectable disease. The patient had experienced disease progression despite multiple chemotherapeutic protocols and several rounds of surgery. After all other treatment options had been exhausted, the patient discovered the pre-clinical evidence of MBZ action against adrenocortical cancer via Pubmed and forwarded the information to the clinicians, who agreed to use it based on this evidence and the relatively low toxicity of treatment. Monotherapy commenced with MBZ
at a typical anti-helminthic dose of 100 mg twice a day. The patient experienced some regression in metastatic lesions, and overall the disease remained stable for 19 months of MBZ monotherapy, tolerating the treatment without side effects, and his quality of life returned to his baseline prior to his initial surgery. However, 24 months after the commencement of oral MBZ a scan showed disease progression, and everolimus was added to the MBZ but without additional benefit in disease control.

A case of metastatic colon cancer treated with MBZ was described by Peter Nygren and Rolf Larsson in 2013 [24]. Here, a 74-year-old patient suffering from progressive metastatic colon cancer had been treated first with capecitabine, oxaliplatin, and bevacizumab, and then by capecitabine and irinotecan in the face of disease progression, and who had no standard treatment options available was started on an oral dose of MBZ of 100 mg twice a day. MBZ was selected based on the author’s previous pre-clinical work with MBZ [20]. After six weeks of monotherapy, radiological evaluation showed near complete remission of metastatic lesions in the lungs and lymph nodes and a good partial remission in the liver. However, the patient experienced elevated liver enzymes (AST and ALT), so MBZ was temporarily stopped and then started at half the dose, with the patient reporting no ill effects. Liver enzymes normalised and a subsequent round of CT scans confirmed the initial disease response. After ceasing treatment for approximately three months, the patient developed brain metastases that were treated with radiotherapy, following by evidence of disease in the lymph nodes. MBZ treatment was not recommenced following the discovery of the brain metastases or in subsequent disease progression. A further five patients have been treated, with one experiencing a minor remission [Private communication from Peter Nygren].


From one study:

Quote:
"Finally, Schmit showed that a range of benzimidazoles, including MBZ, possess anti-neoplastic activity against the DS 17 canine osteosarcoma cell line in vitro [22]. Canine osteosarcoma is an excellent animal model of the human disease. The results obtained showed that MBZ induced cell cycle arrest and apoptosis at MBZ doses that are clinically achievable with oral dosing."


A very interesting thesis on canine osteosarcoma and the benzimidazoles which includes mebendazole:

https://www.ideals.illinois.edu/bitstre ... sequence=1


Quote:
ABSTRACT

The high morbidity and mortality of canine osteosarcoma (OS) despite standard therapy warrants the need to investigate new treatment options. One avenue in exploring novel therapies is drug re-purposing using drugs with known dosing, toxicity profiles, and pharmacokinetics, and re-purposing them “off-label” for their pharmacologic effects for other diseases. In the search for novel therapies for canine osteosarcoma (OS), the benzimidazole(BZ) drug, a class of safe and inexpensive anti-parasitics, were identified as potential novel therapeutics. Benzimidazole (BZ) drugs are used routinely as effective anti-parasitics in both human and veterinary medicine. Their safety is well
established and side effects are minimal in most veterinary species including dogs. Safety has been described both with short-term high doses as well as long-term chronic dosing in dogs and other species with minimal adverse effects. BZs have demonstrated in vitro and in vivo anti-cancer effects in both people and animal tumor models. The mechanism of BZs is thought to be similar to the micro-tubule inhibitory actions of traditional chemo-therapeutic drug classes such as taxanes and vinca alkaloids, leading to metaphase arrest (G2/M phase) and tumor cell apoptosis.BZs also demonstrate indirect anti-cancer activity by vascular disruption of endothelial cells and reduction in cancer cell secretion of the angiogenic cytokine vascular endothelial growth factor (VEGF). In human OS, mitotic spindle inhibitors are routinely used as an adjuvant chemotherapy agent, and similarly mitotic spindle inhibitors demonstrate effect for canine OS. Given the proposed activity at the mitotic apparatus, BZs may have similar activity in canine osteosarcoma. In addition to direct cytotoxic effects, BZs may possess indirect anti-angiogenic effects in canine OS, including modulation of VEGF. In human OS, increased VEGF expression is a negative prognostic factor and a strong predictor of metastasis and poor survival. Similarly serum VEGF is elevated in many canine cancers including OS and correlates with poor disease free interval. This supports a role for VEGF-induced angiogenesis in the development andprogression of metastatic disease in dogs with OS and provides another potential anti-neoplastic mechanism for BZs. We hypothesize that BZs have direct and indirect anti-neoplastic effects in vitro for canine OS. The aims of this study were to assess the in vitro effects of the clinically-used veterinary benzimidazoles [mebendazole (MBZ), fenbendazole (FBZ), and albendazole (ABZ)] iiion a canine OS cell line. Cell lines were evaluated for dose-dependent anti-neoplastic effects on the functions of cell proliferation, cell-cycle phase distribution, and cell death. Soluble VEGF secretion and the effect on tubulin polymerization were also evaluated in vitro. Specifically, the in vitro effects of ABZ, FBZ and MBZ on D17 canine OS cells were investigated by characterizing

1) cell proliferation with an MTS assay,
2) apoptosis via flow cytometry,
3) VEGF secretion via ELISA and
4) tubulin polymerization and 5) cell cycle distribution via flow cytometry.

The results of this study demonstrate that treatment with BZs inhibits cell proliferation in a dose and time dependent fashion. Flow cytometry demonstrates that BZ treatment induces cells arrest in G2/M and subsequently apoptosis. Mechanistically, the BZs affect micro-tubules by inhibition of polymerization. Additionally, exposure to the BZs results in decreased secretion of VEGF from D17 OS cells. Our findings demonstrate that the clinically used veterinary BZs (ABZ, FBZ, and MBZ) possess anti-neoplastic activity in an OS cell line. In addition to direct effects on tubulin polymerization, cell cycle, proliferation, and cytotoxicity, BZs demonstrate indirect activity through modulation of a key pro-angiogenic cytokine. These findings are similar to what we would expect with a traditional mitotic spindle inhibitor such as a vinca alkaloid. In vitro effects are apparent at drug doses achievable in vivo with minimal expected adverse effects.This data supports the continued investigation into the use of BZs as an adjunctive therapy for canine osteosarcom


As far as dosage:

Quote:
Benzimidazole (BZ) drugs have been used for decades in human and veterinary medicine primarily as effective anti-parasitics.11, 12Benzimidazoles have well-established safety and induce minimal adverse side effects in many veterinary species including dogs. Although usually prescribed for short-term usage for parasitic diseases, long-term safety has been reported in dogs at doses from 4mg/kg/day for 180 days to 250 mg/kg/day for 30 days for various BZs with no adverse effects. Recently, BZs have demonstrated additional pharmacologic effects, including in vitro and in vivo anti-cancer activity in both people and animal tumor models.

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