Cancer Papers

Hello Dr. Ward Dean,
My warmest greetings to you, My father Professor Gib Alain of United Kingdom, who is resident here in Abidjan-Ivory Coast, West Africa. Is deeply suffering from prostate cancer disease for long time. He have applied many medications but no remedy yet and his doctor here told him recently that he will not live much longer again because of this disease. But, I believe in God that he can still have a second chance to live, that is why I contacted you personally doctor for your advise and medical assistant. I am looking forward to hearing from you as soon as you can. So, that I can arrange for our trip visit for a better treatment.

Best regards,
Ms. Christine

Hello, Christine,
I’m sorry to hear about your father. I don’t know what stage his condition is, his age, or how his health is otherwise, nor what treatments he has received so far.

Nevertheless, I am attaching a few articles indicating therapies he may be able to obtain in the meantime.

Good luck to you both,
Ward Dean, MD

Reference
Curr Mol Med. 2012 Dec;12(10):1244-52.

Honokiol: a novel natural agent for cancer prevention and therapy.
Arora S1, Singh S, Piazza GA, Contreras CM, Panyam J, Singh AP.
Honokiol (3’,5-di-(2-propenyl)-1,1’-biphenyl-2,4’-diol) is a bioactive natural product derived from Magnolia spp. Recent studies have demonstrated anti-inflammatory, anti-angiogenic, anti-oxidative and anticancer properties of honokiol in vitro and in preclinical models. Honokiol targets multiple signaling pathways including nuclear factor kappa B (NF-κB), signal transducers and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (m-TOR), which have great relevance during cancer initiation and progression. Furthermore, pharmacokinetic profile of honokiol has revealed a desirable spectrum of bioavailability after intravenous administration in animal models, thus making it a suitable agent for clinical trials. In this review, we discuss recent data describing the molecular targets of honokiol and its anti-cancer activities against various malignancies in pre-clinical models. Evaluation of honokiol in clinical trials will be the next step towards its possible human applications.

Free PMC Article
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663139/pdf/nihms-473231.pdf


Modified Citrus Pectin
Inhibition of Cancer Cell Growth and Metastases

By Jim English and Ward Dean, MD
Pectin is a complex carbohydrate (polysaccharide) found in virtually all plants. Pectin helps to bind cells together and provides a structural framework for maintaining the shape and integrity of cell membranes. Recently, a modified form of citrus pectin derived from the pulp and peel of citrus fruits has been shown to attach to cancer cells to prevent them from spreading throughout the body, pointing the way to a potentially safe approach for preventing or reducing cancer metastases.

Spreading Metastases

Conventional cancer treatment involves surgery to remove primary tumors, followed by chemotherapy, radiation, or a combination of treatments designed to eradicate all remaining traces of cancer. This follow-up therapy is critical for addressing the biggest threat from cancer—the formation of secondary cancers, or metastases. Metastases are not new or different cancers, but new cancer colonies started from cells that have migrated to new sites. Sites where metastases commonly occur include the bones, lungs, prostate, kidney, liver, thyroid and brain. Left unchecked, metastases can quickly overwhelm the body’s defenses. In fact, it is metastases, not primary tumors that are responsible for most cancer deaths.

Halting Metastases

Over the last two decades, research into controlling or halting cancer metastases has led to two promising new strategies. The first, antiangiogenesis, targets the growth of new blood vessels (angiogenesis) that are required for tumor growth.1 Originally pioneered by noted cancer researcher Dr. Judah Folkman, the concept of antiangiogenesis developed from his observation that tumors cannot grow without access to a constant supply of new blood vessels.2 Folkman theorized that cancer cells actively communicate with surrounding tissues to trigger the growth of new blood vessels (neovascularization) needed to supply nutrients and remove waste products. Once neovascularization is initiated, hundreds of new capillaries converge on the tumor site and are quickly coated with new layers of rapidly dividing tumor cells.

Folkman also theorized that, just as certain chemical messengers can initiate new capillary formation, other signals could inhibit neovascularization. This insight led to the development of antiangiogenic therapy, which, in contrast to other cancer treatments, doesn’t directly destroy tumors, but aims to limit their blood supply, causing tumors to shrink. By 1997 researchers were excited by promising results from several antiangiogenic drugs. Speaking of one early angiogenesis inhibitor called TNP470, in 1997 Folkman commented on the results of early clinical human trials, stating, “We’ve not seen a tumor that we cannot regress (shrink).”3 Currently TNP470 and several other angiogenesis inhibitors are in clinical trials, and other promising compounds are under study in university laboratories and in some 30 pharmaceutical and biotechnology companies around the world.4

Intercepting Cancer Cells

The second strategy for controlling metastases works by intercepting migrating cancer cells before they have a chance to establish new tumors. This approach targets a family of carbohydrate-binding proteins called lectins.2 Lectins are attracted to sugar molecules found on the surface of almost all cells. Lectins help cancer cells stick together to form multi-celled clusters that are believed to be necessary for metastases formation. Lectins also enable cancer cells to communicate with each other, as well as with other types of cells (cell-to-cell communication) to trigger cellular transformations that assist the spread of cancer. One class of lectin—called galectins (for galactoside-binding lectins)—possesses an especially strong affinity for galactose, a simple sugar located on the surface of cells lining blood vessels.


Oral intake of modified citrus pectin
acts as a “potent inhibitor of
spontaneous prostate cancer
metastasis…”


A number of cancer researchers focused on a particular galectin—galectin-3—that is directly involved in the progression and spread of several types of cancers, including breast, prostate and colon cancer.7,8,12,13 Serum levels of galectin-3 correlate closely with the spread of cancer, and may serve as a biological marker to help physicians and patients monitor the efficacy of anti-cancer therapies.

The Protein-Sugar Connection

The powerful attraction between galectins and galactose plays a pivotal role in how cancers spread in the body. After a cancer cell has broken free from its primary tumor (or is accidentally dislodged during surgery) it floats freely through the blood and lymph systems until it eventually becomes trapped in a small blood vessel (microcapillary). Firmly lodged in the microcapillary, galectins on the surface of the cancer cell start to bind to galactose receptors on endothelial cells (the cells that form the inside lining of blood vessels). After securely attaching to the endothelium the cancer cells penetrate through the blood vessel walls. The final step after invading the vessel involves the release of chemical signals that trigger new blood vessel growth (angiogenesis), and a new tumor colony is firmly established.

Modified Citrus Pectin

Modified citrus pectin (MCP) is a unique dietary fiber that is produced by processing natural citrus pectin by altering its pH and splitting the carbohydrate chains to form a low molecular-weight, water-soluble fiber that is rich in the sugar, galactose. It is this presence of particularly high amounts of galactose that led researchers to wonder if MCP might bind with proteins (lectins) on cancer cells to inhibit their ability to bind with other tissues.

Early test tube studies revealed that MCP did indeed bind to galectins from numerous human cancer cell lines to inhibit their ability to adhere to other cells. Researchers found that as little as a 1.0 percent solution of MCP inhibited attachment of 1) human prostate adenocarcinoma cells, 2) human breast carcinoma cells, 3) human melanoma cells, and 4) human laryngeal epidermoid carcinoma cells to human endothelial cells.10

In 1992, Platt and colleagues demonstrated that MCP was effective at reducing metastases in mice injected with live melanoma cells.15 One group of mice was injected with normal melanoma cells, while a second group received melanoma cells that had been incubated in a solution containing MCP.15 Seventeen days after being injected, the mice receiving untreated melanoma cells were found to have, on average, 33 new tumors (metastases) in their lungs, while the mice receiving the MCP-treated cells had virtually no lung tumors. The researchers hypothesized that MCP had successfully attached to the lectin sites on the cancer cells, blocking the receptors and rendering them incapable of attaching to other cells.

In a second study conducted in 1995, Pienta and colleagues demonstrated that adding MCP to drinking water was an effective delivery route for reducing experimental metastases in rats.14 Four days after injecting rats with live prostate cancer cells, the animals were divided into three groups. Two groups of rats were treated with MCP added to their drinking water in amounts of 0.1% and 1.0%. The animals in the third group, the control, received no MCP. Thirty days after being injected with one million active prostate cancer cells, 15 out of 16 rats in the control (untreated) group had cancer metastases in their lungs, compared with 7 of 14 rats in the 0.1% group, and 9 of 16 in the 1.0% group. Importantly, the 1.0% group had, on average, only one tumor per animal, versus an average of nine tumors in the lungs of the control group. Commenting on the results of the study the researchers noted that oral intake of modified citrus pectin acts as a “potent inhibitor of spontaneous prostate cancer metastasis…”

MCP Exhibits Antiangiogenesis Activity

Fig. 1. Reduction in growth of tumors in modified citrus pectin.
LEM1607WDFig1_274.jpg
(click on thumbnail for full sized image)

A paper published in the December 2002 issue of the Journal of the National Cancer Institute found, as with earlier studies, that MCP significantly reduced both the incidence and the size of tumors in rats injected with human breast cancer and colon cancer cells (Fig. 1).16 Additionally, in vitro experiments found that MCP inhibited formation of capillaries, demonstrating that MCP possesses antiangiogenic properties. Of their findings, the researchers concluded that, “MCP, given orally, inhibits carbohydrate-mediated tumor growth, angiogenesis, and metastasis in vivo, presumably via its effect on galectin-3 function. These data stress the importance of dietary carbohydrate compounds as agents for the prevention and/or treatment of cancer.”17

Conclusion and Dosage Recommendations

There are unfortunately no clinical studies that we are aware of to confirm the efficacy of modified citrus pectin as an anti-cancer substance in humans. Nevertheless, we believe that because of its absolute lack of toxicity in any amount, its demonstrated efficacy in reducing the incidence and size of tumors in experimental animals, and its potential anti-cancer mechanisms as demonstrated in a number of in vitro models, modified citrus pectin should be considered as a key part in any preventive or therapeutic regimen for any type of cancer. Dosage is also speculative, but based on the animal studies, we believe that a dosage of five grams per day may provide significant preventive or therapeutic benefits.

References

1. Al-Mehdi AB, et al. Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat Med. 2000;6:100–2.
2. Hartwell DW, Butterfield CE, Frenette PS, Kenyon BM, Hynes RO, Folkman J, Wagner DD. Angiogenesis in P- and E-selectin-deficient mice. Microcirculation. 1998;5:173–8.
3. Beuth J, et al. Inhibition of liver tumor cell colonization in two animal tumor models by lectin blocking with D-galactose or arabinogalactan. Clin Exp Metastasis. 1988;6:115–20.
4. Hayashi A, Gillen AC, Lott JR. Effects of daily oral administration of quercetin chalcone and modified citrus pectin. Altern Med Rev. 2000;5:546–52.
5. Hensel A, Meier K. Pectins and xyloglucans exhibit antimutagenic activities against nitroaromatic compounds. Planta Med. 1999;65:395–9.
7. Inohara H, Raz A. Effects of natural complex carbohydrate (citrus pectin) on murine melanoma cell properties related to galectin-3 functions. Glycoconj J. 1994;11:527–32.
8. Inufusa H, Nakamura M, Adachi T, Aga M, Kurimoto M, Nakatani Y, et al. Role of galectin-3 in adenocarcinoma liver metastasis. Int J Oncol. 2001;19:913–9.
10. Naik H, Pilat MJ, Donat T, et al. Inhibition of in vitro tumor-cell endothelial adhesion by modified citrus pectin: a pH modified natural complex carbohydrate. Proc Annu Meet Am Assoc Cancer Res. 1995;36:A377.
11. Nangia-Makker P, Baccarini S, Raz A. Carbohydrate-recognition and angiogenesis. Cancer Metastasis Rev. 2000;19:51–7.
12. Nangia-Makker P, et al. Galectin-3 induces endothelial cell morphogenesis and angiogenesis. Am J Pathol. 2000;156:899–909.
13. Nangia-Makker P, et al. The role of galectin-3 in tumor metastasis. In: Lectins and pathology. London (U.K.): Taylor & Francis, Inc.; 2000.
14. Pienta KJ, Naik H, Akhtar A, Yamazaki K, Replogle TS, Lehr J, et al. Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J Natl Cancer Inst. 1995;87:348–53.
15. Platt D, Raz A. Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin. J Natl Cancer Inst. 1992;84:438–42.
16. Pratima Nangia-Makker, Victor Hogan, Yuichiro Honjo, Sara Baccarini, Larry Tait, Robert Bresalier, Avraham Raz. Inhibition of Human Cancer Cell Growth and Metastasis in Nude Mice by Oral Intake of Modified Citrus Pectin. J Natl Cancer Inst. Vol. 94, No. 24, December 18, 2002
17. Raz, A., & Lotan, R. “Endogenous galactoside-binding lectins: A new class of functional tumor cell surface molecules related to metastasis,” Cancer Metastasis Rev. 6: 433-52, 1987.
18. Smith-Barbaro P, Hanson D, Reddy BS. Carcinogen binding to various types of dietary fiber. J Natl Cancer Inst. 1981;67:495–7.
19. Taper HS, Delzenne NM, Roberfroid MB. Growth inhibition of transplantable mouse tumors by non-digestible carbohydrates. Int J Cancer. 1997;71:1109–12.
20. Van den Brule FA, Castronovo V. Laminin binding lectins during invasion and metastasis. In: Lectins and pathology. London (U.K.): Taylor & Francis, Inc.; 2000.


Integr Cancer Ther. 2006 Mar;5(1):83-9.
The long-term survival of a patient with pancreatic cancer with metastases to the liver after treatment with the intravenous alpha-lipoic acid/low-dose naltrexone protocol.
Berkson BM, Rubin DM, Berkson AJ.

The authors describe the long-term survival of a patient with pancreatic cancer without any toxic adverse effects. The treatment regimen includes the intravenous alpha-lipoic acid and low-dose naltrexone (ALA-N) protocol and a healthy lifestyle program.

The patient was told by a reputable university oncology center in October 2002 that there was little hope for his survival. Today, January 2006, however, he is back at work, free from symptoms, and without appreciable progression of his malignancy.

The integrative protocol described in this article may have the possibility of extending the life of a patient who would be customarily considered to be terminal. The authors believe that scientists will one day develop a cure for metastatic pancreatic cancer, perhaps via gene therapy or another biological platform. But until such protocols come to market, the ALA-N protocol should be studied and considered, given its lack of toxicity at levels reported. Several other patients are on this treatment protocol and appear to be doing well at this time.


Prostate. 2015 Aug 1;75(11):1187-96. doi: 10.1002/pros.23000. Epub 2015 Apr 20.
Metformin represses androgen-dependent and androgen-independent prostate cancers by targeting androgen receptor.
Wang Y, Liu G, Tong D, Parmar H, Hasenmayer D, Yuan W, Zhang D, Jiang J.

Metformin has been reported to inhibit the growth of different types of cancers, including prostate cancer. We were interested to understand if the effect of metformin on prostate cancer is AR-dependent and, if so, whether metformin could act synergistically with the other anti-AR agents to serve as a therapeutic regimen with high efficacy and low toxicity.

Cell viabilities and apoptosis were determined by MTT assay and annexin V-FITC staining, respectively, when the two human prostate cancer cell lines, the androgen-dependent LNCaP and the androgen-independent 22RV1 were treated with metformin alone or in combination with bicalutamide. Quantitative RT-PCR and western blotting assays were conducted to examine metformin effects on AR mRNA and protein levels, respectively. Chromatin immunoprecipitation (ChIP) assays were conducted to confirm the recruitment of AR to the ARE(s) located on the promoter region of the AR target gene PSA.

Metformin treatment reduced cell viability and enhanced apoptosis for both cell lines and additive effects were observed when LNCaP cells were treated with combined metformin and bicalutamide. Metformin down-regulated full-length AR protein in LNCaP cells. Both full-length and the truncated AR (AR-v7) were down-regulated by metformin in CWR22Rv1 cells. In both LNCaP and CWR22Rv1 cells, metformin repressed AR signaling pathway not by affecting AR protein degradation/stability, but rather through down-regulating the levels of AR mRNAs.

Metformin represses prostate cancer cell viability and enhances apoptosis by targeting the AR signaling pathway. Combinations of metformin and other anti-AR agents pose a potentially promising therapeutic approach for treatment of prostate cancers, especially the castrate-resistant prostate cancer, with high efficacy and low toxicity.


Prostate Cancer Protocol

Urology. 2009 Jul;74(1):167-70. doi: 10.1016/j.urology.2008.07.067. Epub 2009 May 5.
Does benign prostatic tissue contribute to measurable PSA levels after radical prostatectomy?
Godoy G, Tareen BU, Lepor H.

OBJECTIVES: To determine whether benign prostatic tissue represents a source of measurable prostate-specific antigen (PSA) after radical prostatectomy.

Our criteria for having “extremely” low-risk disease included a preoperative PSA level <10 ng/mL, clinical Stage T1c or T2a, a Gleason score of < or =6, an estimated cancer volume in the specimen of <5%, and no evidence of positive surgical margins. Undetectable PSA was defined as a PSA level of < or =0.04 ng/mL. A measurable PSA level included values between 0.05 and 0.14 ng/mL on > or = 2 consecutive measurements 6 months apart. Biochemical recurrence was defined as 3 consecutively increasing PSA levels with a peak level of > or =0.15 ng/mL.

At 3 months to 6 years of follow-up (mean 36.2 months), 0.6% and 0.3% of patients had developed a measurable PSA level or biochemical recurrence, respectively.

A measurable PSA level or biochemical recurrence was an extraordinarily rare event in our select group of patients with extremely low-risk disease. These results provide compelling evidence that retained benign prostatic elements are an unlikely source of elevated PSA levels in men who have undergone radical prostatectomy.


MEBENDOZOLE (VERMOX)

Good News!

Mebendazole (Vermox) is a medicine that seems too good to be true. And get this—it costs just a couple of dollars. Its anti-cancer success has been well documented in journals—even with cancers that are unresponsive to other chemotherapy. While it kills cancer cells, it poses no harm to the normal cells, and has little or no side effects. It’s called mebendazole, and “Big Pharma” hopes you will never hear about it.

Mebendazole (MBZ)

If you have ever cared for young children then you are probably familiar with this medicine under the name of Vermox, Ovex, Antiox, and Pripsen. It is usually prescribed to treat pinworms, roundworms, whip worms and hookworms—organisms that find an unwelcome home in our intestines.

How it works...

One of the misconceptions that people have about a cell is that it contains a nucleus, a cell wall and everything inside (cytoplasm) kind of sloshes around in a liquid or gel. In fact, the inside of a cell contains a kind of scaffold made of micro-tubules, also called spindles, that have the ability to assemble and disassemble quickly. This network of rigid micro-tubules inside the cell gives it shape, structure and also has the ability to transfer organelles and various molecules to different parts within the cell, functioning like a railway system. But its most vital function is cell division.

Mebendazole is known to interfere and inhibit the assembly of the spindles, thus preventing the ability of the cells to divide. The cell eventually dies of old age or apoptosis. Mebendazole is highly selective and somehow targets only cancerous cells (as well as a host of intestinal parasites). At the end of this article are a few of the many scientific papers acknowledging these facts.

You will also see why there is virtually no pharmaceutical interest in mebendazole. The big pharmaceutical companies are promoting more toxic chemotherapy drugs because there is no profit margin in mebendazole. It’s yet another example of corporate profit outweighing human benefits. Mebendazole is different. It doesn’t kill the cells with poison. It specifically prevents the cell from reproducing.

What has Big Pharma done?

Mebendazole was first synthesized by Janssen Pharmaceutical (later bought by Johnson & Johnson) in 1968. Its value as an anti-worm medicine was recognized and by 1972 mebendazole was being marketed under the name Vermox. Because the prescribed use was eliminating parasites, it was inexpensive and widely used. The selective toxicity of mebendazole to cancerous cells had not yet been discovered.

Back in 1960 the US Government declared war on cancer and funded the Cancer Chemotherapy National Science Center. This agency received over 1000 samples of chemicals—mostly—that were exposed to a variety of animal and human cancer cells.

It must have been like a scene from the movie, Andromeda Strain, where thousands of substances were tested to kill the alien virus brought back in an interstellar probe. With such large sample numbers it was expected that some would prove effective in killing tumors. And that’s exactly what happened.

Same, Same, but Different

Researchers were discovering the value of microtubule inhibitors in 1978. The safest one, mebendazole, was already on the market as a treatment for worms, and it was cheap. For a pharmaceutical company to invest in a cancer cure, it had to make a profit.

A prophylaxis agent?

Before I list the studies, I could not help but wonder why a person wouldn’t take mebendazole periodically in one’s life to purge the body of cancerous cells? It is known to be well tolerated with little toxicity. In some of the studies, mebendazole was taken with Tagamet™ to reduce the metabolizing effects of the liver and increase blood levels. This is an idea that ought to be explored.

Mebendazole is not currently recognized as an anti-cancer drug. The lack of investment by Big Pharma in conducting the many trials and protocols will likely not change this status. But physicians are capable of prescribing the medicine at their own discretion. And ordinary people should be able to secure this medicine themselves.

“Cancer and Vermox”

The Anthelmintic Drug Mebendazole Induces Mitotic Arrest and Apoptosis by Depolymerizing Tubulin in Non-Small Cell Lung Cancer Cells, Ji-ichiro Sasaki,Rajagopal Ramesh,Sunil Chada,Yoshihito Gomyo,Jack A. Roth and Tapas Mukhopadhyay, Molecular Cancer Therapy. November 2002 1; 1201

Epilogue: Discontinued in United States

The last manufacturer of mebendazole in the United States, Teva Pharmaceuticals, announced on October 7, 2011, that they have ceased manufacture of this product. As of December, 2011, it is no longer available from any manufacturer in the USA. No reason was given for this discontinuation, but it’s blatantly obvious.

Mebendazole is available from on-line pharmacies.
http://genericpharminc.be/products/antibiotics/vermox/order/

Here are some references for further research of mebendazole:

The Anthelmintic Drug Mebendazole Induces Mitotic Arrest and Apoptosis by Depolymerizing Tubulin in Non-Small Cell Lung Cancer Cells, Ji-ichiro Sasaki, Rajagopal Ramesh, Sunil Chada,Yoshihito Gomyo, Jack A. Roth and Tapas Mukhopadhyay, Molecular Cancer Therapy November 2002 1; 1201

“... Oral administration of MZ in mice elicited a strong antitumor effect in a s.c. model and reduced lung colonies in experimentally induced lung metastasis without any toxicity when compared with paclitaxel-treated mice. [emphasis added] We speculate that tumor cells may be defective in one mitotic checkpoint function and sensitive to the spindle inhibitor MZ. Abnormal spindle formation may be the key factor determining whether a cell undergoes apoptosis, whereas strong microtubule inhibitors elicit toxicity even in normal cells...”

Mebendazole Elicits a Potent Antitumor Effect on Human Cancer Cell Lines Both in Vitro and in Vivo, Tapas Mukhopadhyay, Ji-ichiro Sasaki, Rajagopal Ramesh, and Jack A. Roth, Clinical Cancer Research. September 2002 8; 2963

“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 G2-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...”

Mebendazole Induces Apoptosis via Bcl-2 Inactivation in Chemoresistant Melanoma Cells, Nicole Doudican, Adrianna Rodriguez, Iman Osman and Seth J. Orlow, Molecular Cancer Research, August 2008 6; 1308

“...Our results suggest that this screening approach is useful for identifying agents that show promise in the treatment of even chemoresistant melanoma and identifies mebendazole as a potent, melanoma-specific cytotoxic agent...”

Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice, Daniele Martarelli, Pierluigi Pompei, Caterina Baldi and Giovanni Mazzoni, Cancer Chemotherapy and Pharmacology, Volume 61, Number 5, 809-817

“Adrenocortical carcinoma is a rare tumor of the adrenal gland which requires new therapeutic approaches as its early diagnosis is difficult and prognosis poor despite therapies used. Recently, mebendazole has been proved to be effective against different cancers. The aim of our study was to evaluate whether mebendazole may be therapeutically useful in the treatment of human adrenocortical carcinoma. We analyzed the effect of mebendazole on human adrenocortical carcinoma cells in vitro and after implantation in nude mice. In order to clarify mechanisms of mebendazole action, metastases formation, apoptosis and angiogenesis were also investigated. Mebendazole significantly inhibited cancer cells growth, both in vitro and in vivo, the effects being due to the induction of apoptosis. Moreover, mebendazole inhibited invasion and migration of cancer cells in vitro, and metastases formation in vivo. Overall, these data suggest that treatment with mebendazole, also in combination with standard therapies, could provide a new protocol for the inhibition of adrenocortical carcinoma growth...”

Mebendazole Monotherapy and Long-Term Disease Control in Metastatic Adrenocortical Carcinoma, Irina Y. Dobrosotskaya, MD, PhD, Gary D. Hammer, MD, David E. Schteingart, MD, Katherine E. Maturen, MD, Francis P. Worden, MD, Endocrine Practice. Volume 17, Number 3 / May-June 2011.

“...A 48-year-old man with adrenocortical carcinoma had disease progression with systemic therapies including mitotane, 5-fluorouracil, streptozotocin, bevacizumab, and external beam radiation therapy. Treatment with all chemotherapeutic drugs was ceased, and he was prescribed mebendazole, 100 mg twice daily, as a single agent. His metastases initially regressed and subsequently remained stable. While receiving mebendazole as a sole treatment for 19 months, his disease remained stable. He did not experience any clinically significant adverse effects, and his quality of life was satisfactory. His disease subsequently progressed after 24 months of mebendazole monotherapy. Conclusion: Mebendazole may achieve long-term disease control of metastatic adrenocortical carcinoma. It is well tolerated and the associated adverse effects are minor....”

Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme, Ren-Yuan Bai, Verena Staedtke, Colette M. Aprhys, Gary L. Gallia and Gregory J. Riggins, Neuro Oncology. (2011) 13(9): 974-982.

“...mebendazole significantly extended mean survival up to 63% in syngeneic and xenograft orthotopic mouse glioma models. Mebendazole has been approved by the US Food and Drug Administration for parasitic infections, has a long track-record of safe human use, and was effective in our animal models with doses documented as safe in humans. Our findings indicate that mebendazole is a possible novel anti-brain tumor therapeutic that could be further tested in clinical trials...

Neuro Oncol. 2011 Sep;13(9):974-82. doi:10.1093/ neuonc/nor077. Epub 2011 Jul 15.
Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme.
Bai RY1, Staedtke V, Aprhys CM, Gallia GL, Riggins GJ.

Glioblastoma multiforme (GBM) is the most common and aggressive brain cancer, and despite treatment advances, patient prognosis remains poor. During routine animal studies, we serendipitously observed that fenbendazole, a benzimidazole antihelminthic used to treat pinworm infection, inhibited brain tumor engraftment. Subsequent in vitro and in vivo experiments with benzimidazoles identified mebendazole as the more promising drug for GBM therapy. In GBM cell lines, mebendazole displayed cytotoxicity, with half-maximal inhibitory concentrations ranging from 0.1 to 0.3 μM. Mebendazole disrupted microtubule formation in GBM cells, and in vitro activity was correlated with reduced tubulin polymerization. Subsequently, we showed that mebendazole significantly extended mean survival up to 63% in syngeneic and xenograft orthotopic mouse glioma models. Mebendazole has been approved by the US Food and Drug Administration for parasitic infections, has a long track-record of safe human use, and was effective in our animal models with doses documented as safe in humans. Our findings indicate that mebendazole is a possible novel anti-brain tumor therapeutic that could be further tested in clinical trials.

Free PMC Article

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158014/


Int J Med Sci. 2008 Mar 24;5(2):62-7.
A 12 week, open label, phase I/IIa study using apatone for the treatment of prostate cancer patients who have failed standard therapy.
Tareen B, Summers JL, Jamison JM, Neal DR, McGuire K, Gerson L, Diokno A.

PURPOSE: To evaluate the safety and efficacy of oral Apatone (Vitamin C and Vitamin K3) administration in the treatment of prostate cancer in patients who failed standard therapy.

Seventeen patients with 2 successive rises in PSA after failure of standard local therapy were treated with (5,000 mg of VC and 50 mg of VK3 each day) for a period of 12 weeks. Prostate Specific Antigen (PSA) levels, PSA velocity (PSAV) and PSA doubling times (PSADT) were calculated before and during treatment at 6 week intervals. Following the initial 12-week trial, 15 of 17 patients opted to continue treatment for an additional period ranging from 6 to 24 months. PSA values were followed for these patients.

At the conclusion of the 12 week treatment period, PSAV decreased and PSADT increased in 13 of 17 patients (p < or = 0.05). Of the 15 patients who continued on Apatone after 12 weeks, only 1 death occurred after 14 months of treatment.

Apatone showed promise in delaying biochemical progression in this group of end stage prostate cancer patients.

Misc. References:

  • Guess BW, Scholz MC, Strum SB, Lam RY, Johnson HJ, Jennrich RI. Modified citrus pectin (MCP) increases the prostate-specific antigen doubling time in men with prostate cancer: a phase II pilot study. Prostate Cancer and Prostatic Dis. 2003;6:301
  • Lasalvia-Prisco E, Cucchi S, Vazquez J, Lasalvia-Galante E, Golomar W, Gordon W. Serum markers variation consistent with autoschizis induced by ascorbic acid-menadione in patients with prostate cancer. Med Oncol. 2003;20:45
  • De Loecker W, Janssens J, Bonte J, Taper HS. Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. II. Synergism with combined chemotherapy action. Anticancer Res. 1993;13:103
  • Jamison JM, Gilloteaux J, Taper HS, Buc Calderon P, Perlaky L, Thiry M. et al. The in vitro and in vivo antitumor activity of vitamin C: K3 combinations against prostate cancer. In: (ed.) Lucas JL. Trends in prostate cancer research. Hauppauge, NY: Nova Science Publishers. 2005:189-236.
  • Gilloteaux J, Jamison JM, Neal DR, Summers JL. Cell death by autoschizis in TRAMP prostate carcinoma cells as a result of treatment by ascorbate: menadione combination. Ultrastruct Pathol. 2005;29:221.

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