Pancreatic and Hepatic Fibrosis: Remarkable Similarities

HemsworthPeterson, Theresa C

doi:10.4172/2165-7092.1000e111

Cited by 2 publications

(3 citation statements)

References 17 publications

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“…Our work in the gastrointestinal system specifically in collagenous colitis, (Figure 3) and our results obtained in liver disorders (including but not limited to hepatitis C and other hepatic fibrotic diseases) clearly indicate that platelet derived growth factor plays a key role [16]. While it is true that other major growth factors are involved, it appears that the fine-tuning of the fibrotic mechanism is under the influence of platelet derived growth factor.…”

Section: Introductionsupporting

confidence: 57%

“…It is time to take another look at how we develop drugs to treat disorders and perhaps accept that we can never totally understand the mechanism and clinical complexities of the disease. Instead, we should use some broad strokes to target what we shall call a fatal flaw in the disease mechanism, and pair that with a powerful antioxidant agent which will boost patients' ability to fight the disease [11][12][13][14][15][16][17][18][19]. It is likely that combination therapy has the potential to change the future of clinical therapeutics, especially since RCTs already show antioxidant benefit.…”

Section: Introductionmentioning

confidence: 99%

“…With over 35 years of studies in the field of inflammation and fibrosis in other organ systems (including the liver and the gastrointestinal system, fibrotic studies in lung and collagen deposition studies in cardiac tissue and brain), the wealth of information generated by those studies and subsequent publications should now be applied effectively to studying pancreatic disorders including pancreatitis, pancreatic fibrosis and ultimately pancreatic cancer [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Novel Combination Therapy Boosts the Host Immune System, Destroys Free Radicals and Targets the Critical Flaw in Chronic Pancreatic Disease

Peterson¹

2016

Pancreat Disord Ther

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Aim: To investigate the role of combination therapy using the cytokines antagonist, pentoxifylline in combination with a novel powerful antioxidant derived from grape product in the treatment of pancreatic disease. Methods and Research Plan:We want to acknowledge that much of the groundwork has already been done demonstrating the positive effect of antioxidant therapy in pancreatic diseases including pancreatitis, chronic pancreatic disorders, fibrosis and even pancreatic cancer. It is also well accepted that pentoxifylline, originally described as a drug to aid blood circulation via actions on adenosine triphosphate, is also an effective and efficient inhibitor of platelet derived growth factor and other cytokines essential to the inflammatory and fibrotic processes. We have understood for several years that this immunopharmacological drug inhibits other key signalling molecules in the immune system, ultimately preventing the collagen synthesis and deposition which is critical in pancreatic, hepatic and intestinal fibrosis. Our aim is to combine these two forms of therapy in patients with chronic pancreatic disease while simultaneously optimizing conditions using as our basis the dramatic results that have already been reported widely in literature, by world class investigators. Results and Conclusion:Results to date are promising. Our results presented here clearly indicate that pentoxifylline will block a process in a relatively rare form of intestinal fibrosis called collagenous colitis. This was our proof of concept. In this very selective disease the critical step is collagen deposition. Collagen synthesis resulting in deposition is the key factor involved and has a direct effect on the outcome in these patients with collagenous colitis. We were able to show that pentoxifylline would effectively reduce collagen deposition in the colons of a group of relatively heterogeneous patients with their one consistent variable being biopsy proven colonic collagen deposition and an elevated FSI or fibrogenic stimulation index. Our results also clearly indicate that the reduction in colonic collagen deposition occurring with pentoxifylline therapy is accompanied by a measurable DII or drug inhibition index and that the FSI was predictive of which cohort of patients would respond to this drug. Pentoxifylline was an effective anti-fibrotic agent while having little if any side effect and working in a very effective way to reduce the signs and symptoms of the disease. Long before we were able to see the histological proof in colonic biopsies, patients who prior to treatment showed a predictive DII were already reporting beneficial effects on their symptoms and clinicians were reporting improvement in clinical signs. At time points during the treatment period, biopsies revealed that the collagen was diminishing and results also indicate that the rate of reduction of collagen deposition related to the chronicity of the disease itself. The combination of a novel antioxidant derived from grapes together with the drug...

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Section: Introductionsupporting

confidence: 57%