Animal Study Finds Tiny Dose of Sildenafil (Viagra) May Reduce Colon Cancer Risk

MedicalResearch.com Interview with:

Darren D. Browning, PhD | Professor Department of Biochemistry and Molecular Biology, Medical College of Georgia at Augusta University Georgia Cancer Center, Augusta, Georgia 30912-2100

Dr. Darren Browning

Darren D. Browning, PhD | Professor
Department of Biochemistry and Molecular Biology,
Medical College of Georgia at Augusta University
Georgia Cancer Center,
Augusta, Georgia 30912-2100

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cancer of the colon and rectum is one of the most commonly diagnosed and has a high mortality because it is often identified at an advanced stage. In the United States the average overall risk of having to deal with this disease at some point is around one in twenty-five, but the risk is much higher for people who have previously had polyps removed or if a close relative was diagnosed with colon cancer. The risk is even higher for patients with inflammatory bowel disease or heritable disorders such as familial adenomatous polyposis and lynch syndrome. While chemoprevention is clearly warranted, there are currently no drugs available that can reduce the risk for those predisposed to colorectal cancer.

Previous work from our laboratory has shown that drugs like sildenafil that inhibit phosphodiesterase 5 (PDE5), have a profound effect on the epithelial lining of the intestine. Our recent work has shown that these drugs can prevent intestinal cancers in two different mouse models of human disease. While this class of drugs is best known for treating erectile dysfunction, due to a low side-effect profile they are also prescribed for long-term daily use to treat pulmonary arterial hypertension (PAH) and benign prostate hyperplasia

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Larger Study Finds No Link Between Melanoma and Viagra

Dr. Stacy Loeb, MD, MScDepartment of Urology, Population Health, and Laura and Isaac Perlmutter Cancer CenterNew York University, New York MedicalResearch.com Interview with:
Dr. Stacy Loeb, MD, MSc
Department of Urology, Population Health,
and Laura and Isaac Perlmutter Cancer Center
New York University, New York

Medical Research: What is the background for this study?

Dr. Loeb: A paper published last year suggested a relationship between use of sildenafil (Viagra) and melanoma.  That study had only 142 cases of melanoma, and of these men 14 had used sildenafil.  This study got a lot of publicity leading numerous patients to express concern over whether erectile dysfunction drugs could cause melanoma.

Our goal was to look more closely at this issue in a larger population from Sweden (including 4065 melanoma cases of whom 435 used any type of erectile dysfunction drug- Viagra, as well as Levitra and Cialis).  Sweden has a national health system so we were able to access prescription records for men across the entire country, which we linked to the national registries for melanoma and basal cell skin cancer.   Continue reading

Viagra Derivatives May Block Malaria Transmission

MedicalResearch.com Interview with:
Dr. Gordon Langsley
Laboratoire de Biologie Cellulaire Comparative des Apicomplexes,
Institut Cochin, INSERM U1016, CNRS UMR 8104,
Faculté de Medecine
Université Paris Descartes, Paris

Medical Research: What is the background for this study? What are the main findings?

Response: We have been studying the role of cAMP-dependent PKA signaling in Plasmodium falciparum-infected red blood cells for some time; see just a few examples: PMID: 25522250; PMID: 22626931; PMID: 18248092; PMID: 11559352 and we came to the conclusion that intra cellular cAMP levels regulate infected red blood cell deformability and adhesion to for example, brain endothelial cells.

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Potential Drug Combination With Viagra May Enhance Cancer and Infection Treatments

Paul Dent PhD Massey Cancer Center, Departments of Biochemistry and Molecular Biology Virginia Commonwealth University, Richmond, VA 23298MedicalResearch.com Interview with:
Paul Dent PhD
Massey Cancer Center,
Departments of Biochemistry and Molecular Biology
Virginia Commonwealth University, Richmond, VA 23298

Medical Research: What is the background for this study? What are the main findings?


Dr. Dent: I have worked on understanding how the drug OSU-03012 (AR-12) kills cancer cells since 2005.

The drug was originally advertised as an inhibitor of PDK1 in the PI3 kinase pathway. We found that PDK1 inhibition could not be the major way in which the drug worked. We found that the drug killed brain cancer cells through endoplasmic reticulum stress signaling. And in 2012 we published that OSU-03012 destabilized the chaperone protein GRP78, without significantly altering its transcription. Loss of GRP78 was responsible for the prolonged intense endoplasmic reticulum stress signal, that was toxic. In 2014 we published that OSU-03012 + Viagra / Cialis synergized to kill brain cancer cells. We hypothesized that Viagra / Cialis might enhance the anti-GRP78 effect of OSU-03012; and this was proven to be true.

We discovered that the OSU-03012 + Viagra combination, but not OSU-03012 alone, reduced expression of other chaperone proteins, such as HSP70, GRP94. In mice, the combination was not toxic to “normal” tissues, but was toxic to tumor cells.

In human patients the drug was found to be safe in a phase I trial, with plasma levels of up to 8 microM, and patients on trial for up to 9 months.

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Does Long Term Viagra Improve Heart Disease?

Dr. Andrea M. Isidori, MD, PhD Consultant - Assistant Professor of Endocrinology Department of Experimental Medicine Medical Pathophysiology Sapienza University of RomeMedicalResearch.com Interview with:
Dr. Andrea M. Isidori, MD, PhD
Consultant – Assistant Professor of Endocrinology
Department of Experimental Medicine
Medical Pathophysiology
Sapienza University of Rome

Medical Research: What is the background for this study? What are the main findings?

Dr. Isidori : Our meta-analytic research originated to clarify some controversies emerging from the available human studies. We wanted to analyze if chronic PDE5i administration was cardioprotective and safe, and, if so, where the benefits were mainly seen: cardiac muscle, peripheral vessels, or both. In the last sixteen years pre-clinical and clinical research into the extra-urological effects of PDE5i has expanded dramatically, revealing previously unsuspected indications for these drugs. Several animal studies have shown that PDE5i attenuates cardiac remodeling, with an anti-hypertrophic and anti-fibrotic effect, and protects the heart against different types of injury. Some small clinical trials have demonstrated that chronic PDE5 inhibition improves cardiac performance and geometry in various clinical conditions, including heart failure, myocardial infarction and diabetic cardiomyopathy.

We showed that continuous administration of Viagra improves cardiac performance (increase of ejection fraction and cardiac index) and has an anti-remodeling effect (decrease of left ventricular mass and increase of end diastolic volume) without a major impact on vascular parameters (blood pressure and vascular resistance) suggesting that it does indeed have a direct effect on the heart. The novelty of this meta-analysis is the identification of subgroups of patients that may benefit more from PDE5i: patients with cardiac hypertrophy and heart failure. Our study is the first to show in a large patient cohort that chronic PDE5i administration improves cardiac output and decreases heart rate. This could result in longer survival, increased exercise tolerance and a better quality of life. Surprisingly, the magnitude of effects was similar to that seen with the drugs currently used to treat these clinical conditions, and was obtained in a relatively brief period (3 to 12 months). Most strikingly, we found that PDE5is are among the very few drugs that are able to improve diastolic relaxation, thus helping the correct refilling of the ventricle after each contraction, a nearly unique feature in drugs used in cardiology, and with incredible potential for future development in the prevention of heart failure. We also demonstrated their high tolerability and safety in a population that included elderly patients with various stages of cardiac disease and numerous comorbidities who were taking multiple pharmacological treatments. This setting resembles what we normally see in real life, supporting that daily administration is safe and involves no increase in the risk of adverse events compared to on-demand use.
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