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Inositol Hexaphosphate (IP6) and Colon Cancer: From Concepts and First Experiments to Clinical Application.
Vucenik, I, Druzijanic, A, Druzijanic, N
Molecules (Basel, Switzerland). 2020;(24)
Abstract
Multiple human health-beneficial effects have been related to highly phosphorylated inositol hexaphosphate (IP6). This naturally occurring carbohydrate and its parent compound, myo-inositol (Ins), are abundantly present in plants, particularly in certain high-fiber diets, but also in mammalian cells, where they regulate important cellular functions. However, the striking and broad-spectrum anticancer activity of IP6, consistently demonstrated in different experimental models, has been in a spotlight of the scientific community dealing with the nutrition and cancer during the last several decades. First experiments were performed in colon cancer 30 years ago. Since then, it has been shown that IP6 reduces cell proliferation, induces apoptosis and differentiation of malignant cells with reversion to normal phenotype, affecting several critical molecular targets. Enhanced immunity and antioxidant properties also contribute to the tumor cell destruction. Although Ins possesses a modest anticancer potential, the best anticancer results were obtained from the combination of IP6 + Ins. Here we review the first experimental steps in colon cancer, when concepts and hypotheses were put together almost without real knowledge and present clinical studies, that were initiated in colon cancer patients. Available as a dietary supplement, IP6 + Ins has been shown to enhance the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves quality of life in cancer patients. Emerging clinical and still vast amount of experimental data suggest its role either as an adjuvant or as an "alternative" to current chemotherapy for cancer.
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Effect of preoperative immunonutrition on outcomes of colon cancer surgery: study protocol for a randomized controlled trial.
Lee, SY, Yeom, SS, Kim, CH, Kim, HR
Trials. 2020;(1):628
Abstract
BACKGROUND Current guidelines recommend the prescription of immune-enriched oral nutritional supplements for malnourished patients before major gastrointestinal surgery. However, the benefit of preoperative immunonutrition is still controversial. This randomized controlled trial aims to evaluate the effect of preoperative immunonutrition on the outcomes of surgery for colon cancer. METHODS/DESIGN Patients with primary colon cancer will be included as study participants after screening. They will be randomly assigned (in a ratio of 1:1) to receive preoperative immunonutrition added to the normal diet (experimental arm) or consume normal diet alone (control arm). Patients in the experimental arm will receive oral supplementation (400 mL/day) with arginine and ω-3 fatty acids for 7 days before elective surgery. The primary endpoint is the rate of infectious complications, while the secondary endpoints are postoperative complication rate, change in body weight, length of hospital stay, and nature of fecal microbiome. The authors hypothesize that the rate of infectious complications would be 13% in the experimental arm and 30% in the control arm. With a two-sided alpha of 0.05 and a power of 0.8, the sample size is calculated as 176 patients (88 per arm). DISCUSSION Although there have been many studies demonstrating significant benefits of preoperative immunonutrition, these were limited by a small sample size and potential publication bias. Despite the recommendation of immunonutrition before surgery in nutritional guidelines, its role in reduction of rate of infectious complications is still controversial. This trial is expected to provide evidence for the benefits of administration of preoperative immunonutrition in patients with colon cancer. TRIAL REGISTRATION Clinical Research Information Service KCT0003770 . Registered on 15 April 2019.
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The colonic microbiota in health and disease.
Shanahan, F
Current opinion in gastroenterology. 2013;(1):49-54
Abstract
PURPOSE OF REVIEW Diverse research interests have converged on the gut microbiota because of its contribution to immune development, mucosal homeostasis and to the pathogenesis of a diversity of intestinal and extraintestinal disorders. Recent landmark findings are addressed here. RECENT FINDINGS The impact of lifestyle, including dietary changes and antibiotics, on the microbiota has been mechanistically linked with disease risk. Microbial, immune and metabolic signalling are mutually interactive, with each of these being regulated by diet. Although changes in the microbiota have been found in several disorders and may have important therapeutic implications, some components of the commensal microbiota may behave like pathogens (pathobionts) depending on the context and host susceptibility. SUMMARY Advances in understanding host-microbe interactions in the gut continue apace, they are relevant to a diversity of infectious, inflammatory, neoplastic and metabolic disorders and are poised for clinical translation.
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Mechanisms linking obesity, inflammation and altered metabolism to colon carcinogenesis.
Yehuda-Shnaidman, E, Schwartz, B
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2012;(12):1083-95
Abstract
Due to its prevalence, obesity is now considered a global epidemic. It is linked to increased risk of colorectal cancer, the third most common cancer and the second leading cause of death among adults in Western countries. Obese adipose tissue differs from lean adipose tissue in its immunogenic profile, body fat distribution and metabolic profile. Obese adipose tissue releases free fatty acids, adipokines and many pro-inflammatory chemokines. These factors are known to play a key role in regulating malignant transformation and cancer progression. Obese adipose tissue is infiltrated by macrophages that participate in inflammatory pathways activated within the tissue. Adipose tissue macrophages consist of two different phenotypes. M1 macrophages reside in obese adipose tissue and produce pro-inflammatory cytokines, and M2 macrophages reside in lean adipose tissue and produce anti-inflammatory cytokines, such as interleukin-10 (IL-10). The metabolic networks that confer tumour cells with their oncogenic properties, such as increased proliferation and the ability to avoid apoptosis are still not well understood. We review the interactions between adipocytes and immune cells that may alter the metabolism towards promotion of colorectal cancer.
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The colonic microbiota and colonic disease.
Shanahan, F
Current gastroenterology reports. 2012;(5):446-52
Abstract
The colonic ecosystem differs from that in the proximal gut in several important respects. The colonic microbiota represents the largest population of microbes colonizing humans from birth. Constraints on bacterial numbers, composition, and interaction with the host involve not only the innate and acquired immune system, but also the colonic mucin structure. While the microbiota provides beneficial protective, trophic, nutritional, and metabolic signals for the host, it may become a risk factor for disease depending on context and host susceptibility. Technological advances including DNA-based high-throughput compositional analysis have linked changes in the indigenous microbiota with several human diseases. In some instances, these findings have the potential to serve as new biomarkers of risk of disease. In this overview, recent advances are focused upon in relation to irritable bowel syndrome, inflammatory bowel disease, and colon cancer. The possibility that the therapeutic solution to some of these disorders may reside within the microbiota will also be addressed.
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Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer.
Ishikawa, H, Saeki, T, Otani, T, Suzuki, T, Shimozuma, K, Nishino, H, Fukuda, S, Morimoto, K
The Journal of nutrition. 2006;(3 Suppl):816S-820S
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Abstract
Aged garlic extract (AGE) has manifold biological activities including immunomodulative and antioxidative effects. It is used as a major component of nonprescription tonics and cold-prevention medicines or dietary supplements. Advanced-cancer patients decline in immune functions and quality of life (QOL). The study's subjects were patients with inoperable colorectal, liver, or pancreatic cancer. In a randomized double-blind trial, AGE was administered to one group and a placebo was administered to another for 6 mo. The primary endpoint was a QOL questionnaire based on the Functional Assessment of Cancer Therapy (FACT). The subendpoints were changes in the natural-killer (NK) cell activity the salivary cortisol level from before and after administering AGE. Out of 55 patients invited to participate in the trial, 50 (91%) consented to enroll. They consisted of 42 patients with liver cancer (84%), 7 patients with pancreatic cancer (14%), and 1 patient with colon cancer (2%). Drug compliance was relatively good in both the AGE and placebo groups. Although no difference was observed in QOL, both the number of NK cells and the NK cell activity increased significantly in the AGE group. No adverse effect was observed in either group. The study showed that administering AGE to patients with advanced cancer of the digestive system improved NK cell activity, but caused no improvement in QOL.
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Olive oil as a functional food: epidemiology and nutritional approaches.
Stark, AH, Madar, Z
Nutrition reviews. 2002;(6):170-6
Abstract
Olive oil is an integral ingredient of the Mediterranean diet and accumulating evidence suggests that it may have health benefits that include reduction of risk factors of coronary heart disease, prevention of several varieties of cancers, and modification of immune and inflammatory responses. Olive oil appears to be an example of a functional food, with varied components that may contribute to its overall therapeutic characteristics. Olive oil is known for its high levels of monounsaturated fatty acids and is also a good source of phytochemicals including polyphenolic compounds, squalene, and alpha-tocopherol.