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1.
The Potential Clinical Value of Curcumin and its Derivatives in Colorectal Cancer.
Yao, Z, Le, TH, Du, Q, Mu, H, Liu, C, Zhu, Y
Anti-cancer agents in medicinal chemistry. 2021;(13):1626-1637
Abstract
BACKGROUND Curcumin, a naturally occurring polyphenol, possesses pleiotropic pharmacologic properties, including anti-inflammatory and anti-oxidant activities. Epidemiological evidence suggests that curcumin intake is associated with a reduced risk of Colorectal Cancer (CRC), highlighting the enormous potential of this botanical agent in the prevention and treatment of CRC. OBJECTIVE We summarize the anticancer activity of curcumin and its derivatives in CRC. METHODS We conducted a literature review on the therapeutic effects of curcumin and its derivatives in CRC. RESULTS In this review, a summary of the activities of curcumin in the treatment of CRC regarding its bioavailability, anticancer activity, modes of action, curcumin delivery systems have been provided based on the researches from preclinical experiments. Also, we discuss the therapeutic effects of curcumin derivatives in CRC. The human clinical trials that used curcumin or curcumin derivatives for the treatment of CRC are also highlighted here. CONCLUSION Curcumin possesses great potential as a chemopreventive agent in CRC. Moreover, emerging evidence reveals that it can be an effective adjuvant to CRC therapy. To date, few studies have explored the anticolon cancer activity of curcumin formulation and curcumin derivatives in vivo; therefore, more works are needed to confirm their effectiveness. In clinical trials, curcumin treatment protocols (formulation, dose, and duration) vary among studies. However, these trials consistently point out that the compound is well-tolerated and safe, albeit with little consensus on its therapeutic efficacy.
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2.
Preoperative malnutrition in patients with colorectal cancer.
Gupta, A, Gupta, E, Hilsden, R, Hawel, JD, Elnahas, AI, Schlachta, CM, Alkhamesi, NA
Canadian journal of surgery. Journal canadien de chirurgie. 2021;(6):E621-E629
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Abstract
Preoperative malnutrition in patients with colorectal cancer is associated with several postoperative consequences and poorer prognosis. Currently, there is a lack of a universal screening tool to assess nutritional status, and intervention to treat preoperative malnutrition is often neglected. This review summarizes and compares preoperative screening and interventional tools to help providers optimize malnourished patients with colorectal cancer for surgery. We found that nutritional screenings, such as the Subjectibe Global Assessment, Patient-Generated Subjective Global Assessment, Prognostic Nutritional Index, Nutrition Risk Index, Malnutrition Universal Screening Tool, Nutrition Risk Screening 2002, Nutrition Risk Score, serum albumin, and prealbumin, have all effectively predicted postoperative outcome. Physicians should consider which of these tools best fits their needs based on the their mode of assessment, efficiency, and specified parameters. Additionally, preoperative nutritional support, such as trimodal prehabilitation, modified peripheral parenteral nutrition, and N-3 fatty acid and arginine supplementation, which have also benefited patients postoperatively, ought to be implemented appropriately according to their ease of execution. Given the high prevalence of preoperative malnutrition in patients undergoing surgery for colorectal cancer, it is essential that health care providers assess and treat this malnutrition to reduce postoperative complications and length of hospital stay, and to improve prognosis to augment a patient's quality of care.La malnutrition préopératoire chez les patients atteints d'un cancer colorectal est associée à plusieurs complications postopératoires et à un pronostic plus sombre. Il n'existe actuellement aucun outil universel d'évaluation du statut nutritionnel, et les mesures visant à corriger la malnutrition préopératoire font souvent défaut. La présente revue résume et compare les outils de dépistage et d'intervention préopératoires pour aider les professionnels à améliorer l'état des patients dénutris qui doivent subir une chirurgie pour le cancer colorectal. Nous avons constaté que le dépistage nutritionnel à l'aide de questionnaires tels que l'Évaluation globale subjective, l'Index nutritionnel pronostique, l'Outil universel de dépistage de la malnutrition, NRS 2002 (Nutrition Risk Screening 2002), l'évaluation du risque nutritionnel, et le dosage de l'albumine et de la préalbumine sériques, a permis de prédire avec justesse l'issue de la chirurgie. Les médecins devraient vérifier lequel de ces outils est le mieux adapté à leurs besoins selon leur modalité d'évaluation, leur efficience et autres paramètres spécifiques. Également, un soutien nutritionnel préopératoire, comme la préadaptation trimodale, la nutrition parentérale périphérique modifiée et les suppléments d'acides gras N-3 et d'arginine, qui ont aussi donné des résultats postopératoires favorables, devrait être appliqué selon sa facilité d'administration. Étant donné la forte prévalence de la malnutrition préopératoire chez les patients soumis à une chirurgie pour cancer colorectal, les professionnels de la santé se doivent d'évaluer et de corriger la malnutrition afin de prévenir les complications postopératoires, d'abréger la durée du séjour hospitalier, et d'améliorer ainsi le pronostic et la qualité des soins.
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Gut microbiota alterations are distinct for primary colorectal cancer and hepatocellular carcinoma.
Jia, W, Rajani, C, Xu, H, Zheng, X
Protein & cell. 2021;(5):374-393
Abstract
Colorectal cancer (CRC) and hepatocellular carcinoma (HCC) are the second and third most common causes of death by cancer, respectively. The etiologies of the two cancers are either infectious insult or due to chronic use of alcohol, smoking, diet, obesity and diabetes. Pathological changes in the composition of the gut microbiota that lead to intestinal inflammation are a common factor for both HCC and CRC. However, the gut microbiota of the cancer patient evolves with disease pathogenesis in unique ways that are affected by etiologies and environmental factors. In this review, we examine the changes that occur in the composition of the gut microbiota across the stages of the HCC and CRC. Based on the idea that the gut microbiota are an additional "lifeline" and contribute to the tumor microenvironment, we can observe from previously published literature how the microbiota can cause a shift in the balance from normal → inflammation → diminished inflammation from early to later disease stages. This pattern leads to the hypothesis that tumor survival depends on a less pro-inflammatory tumor microenvironment. The differences observed in the gut microbiota composition between different disease etiologies as well as between HCC and CRC suggest that the tumor microenvironment is unique for each case.
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The Effect of Perioperative Administration of Probiotics on Colorectal Cancer Surgery Outcomes.
Pitsillides, L, Pellino, G, Tekkis, P, Kontovounisios, C
Nutrients. 2021;(5)
Abstract
The perioperative care of colorectal cancer (CRC) patients includes antibiotics. Although antibiotics do provide a certain protection against infections, they do not eliminate them completely, and they do carry risks of microbial resistance and disruption of the microbiome. Probiotics can maintain the microbiome's balance postoperatively by maintaining intestinal mucosal integrity and reducing bacterial translocation (BT). This review aims to assess the role of probiotics in the perioperative management of CRC patients. The outcomes were categorised into: postoperative infectious and non-infectious complications, BT rate analysis, and intestinal permeability assessment. Fifteen randomised controlled trials (RCTs) were included. There was a trend towards lower rates of postoperative infectious and non-infectious complications with probiotics versus placebo. Probiotics reduced BT, maintained intestinal mucosal permeability, and provided a better balance of beneficial to pathogenic microorganisms. Heterogeneity among RCTs was high. Factors that influence the effect of probiotics include the species used, using a combination vs. single species, the duration of administration, and the location of the bowel resection. Although this review provided evidence for how probiotics possibly operate and reported notable evidence that probiotics can lower rates of infections, heterogeneity was observed. In order to corroborate the findings, future RCTs should keep the aforementioned factors constant.
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Performance of capecitabine in novel combination therapies in colorectal cancer.
Pouya, FD, Rasmi, Y, Camci, IY, Tutar, Y, Nemati, M
Journal of chemotherapy (Florence, Italy). 2021;(6):375-389
Abstract
Colorectal cancer is one of the most common cancers throughout the world, and no definitive cure has ever been found. Perhaps a new insight into the effectiveness of chemotherapy drugs could help better treat patients. Targeted therapies have significantly improved the median overall survival of colorectal cancer patients. One of the standard chemotherapy regimens used for colorectal cancer is capecitabine, which is important in monotherapy and combination therapies. Capecitabine, with other chemotherapeutic agents (irinotecan, oxaliplatin, perifosine, 17-allylamino-17-demethoxygeldanamycin, aspirin, celecoxib, statins, quinacrine, inositol hexaphosphate and inositol, cystine/theanine, curcumin, and isorhamnetin), and biological ones (antibodies) plays an important role in the inhibition of some signaling pathways, increasing survival, reducing tumor growth and side effects of capecitabine. However, some drugs, such as proton pump inhibitors, are negatively related to capecitabine; therefore, the purpose of this work is to review and discuss the performance of capecitabine combination therapies in colorectal cancer.
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Dietary Fatty Acids at the Crossroad between Obesity and Colorectal Cancer: Fine Regulators of Adipose Tissue Homeostasis and Immune Response.
Del Cornò, M, Varì, R, Scazzocchio, B, Varano, B, Masella, R, Conti, L
Cells. 2021;(7)
Abstract
Colorectal cancer (CRC) is among the major threatening diseases worldwide, being the third most common cancer, and a leading cause of death, with a global incidence expected to increase in the coming years. Enhanced adiposity, particularly visceral fat, is a major risk factor for the development of several tumours, including CRC, and represents an important indicator of incidence, survival, prognosis, recurrence rates, and response to therapy. The obesity-associated low-grade chronic inflammation is thought to be a key determinant in CRC development, with the adipocytes and the adipose tissue (AT) playing a significant role in the integration of diet-related endocrine, metabolic, and inflammatory signals. Furthermore, AT infiltrating immune cells contribute to local and systemic inflammation by affecting immune and cancer cell functions through the release of soluble mediators. Among the factors introduced with diet and enriched in AT, fatty acids (FA) represent major players in inflammation and are able to deeply regulate AT homeostasis and immune cell function through gene expression regulation and by modulating the activity of several transcription factors (TF). This review summarizes human studies on the effects of dietary FA on AT homeostasis and immune cell functions, highlighting the molecular pathways and TF involved. The relevance of FA balance in linking diet, AT inflammation, and CRC is also discussed. Original and review articles were searched in PubMed without temporal limitation up to March 2021, by using fatty acid as a keyword in combination with diet, obesity, colorectal cancer, inflammation, adipose tissue, immune cells, and transcription factors.
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Fibronectin and colorectal cancer: signaling pathways and clinical implications.
Wang, J, Li, R, Li, M, Wang, C
Journal of receptor and signal transduction research. 2021;(4):313-320
Abstract
Colorectal cancer (CRC) is the fourth leading cause of cancer deaths worldwide, with poor prognosis mainly related to metastasis. Fibronectin (FN), a vital component of the extracellular matrix (ECM), has been found involved in tumorigenesis and malignant progression in different types of malignancy. Numerous studies have indicated the distinct expression of FN in various cancers and demonstrated the different functions of FN in the proliferation, migration, and invasion of cancers. Meanwhile, FN isoforms have been extensively used for targeted drug delivery and imaging for tumors. Although a growing number of studies on FN in CRC have been reported, integrated reviews on the relationship between FN and CRC are rare. In this review, we will summarize the association between FN and CRC, including the signaling pathways and molecules involved in, as well as potential diagnostic and therapeutic values of FN for patients with CRC.
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Dietary Factors Modulating Colorectal Carcinogenesis.
Vernia, F, Longo, S, Stefanelli, G, Viscido, A, Latella, G
Nutrients. 2021;(1)
Abstract
The development of colorectal cancer, responsible for 9% of cancer-related deaths, is favored by a combination of genetic and environmental factors. The modification of diet and lifestyle may modify the risk of colorectal cancer (CRC) and prevent neoplasia in up to 50% of cases. The Western diet, characterized by a high intake of fat, red meat and processed meat has emerged as an important contributor. Conversely, a high intake of dietary fiber partially counteracts the unfavorable effects of meat through multiple mechanisms, including reduced intestinal transit time and dilution of carcinogenic compounds. Providing antioxidants (e.g., vitamins C and E) and leading to increased intraluminal production of protective fermentation products, like butyrate, represent other beneficial and useful effects of a fiber-rich diet. Protective effects on the risk of developing colorectal cancer have been also advocated for some specific micronutrients like vitamin D, selenium, and calcium. Diet-induced modifications of the gut microbiota modulate colonic epithelial cell homeostasis and carcinogenesis. This can have, under different conditions, opposite effects on the risk of CRC, through the production of mutagenic and carcinogenic agents or, conversely, of protective compounds. The aim of this review is to summarize the most recent evidence on the role of diet as a potential risk factor for the development of colorectal malignancies, as well as providing possible prevention dietary strategies.
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Nutritional prevention of colorectal cancer.
Hull, MA
The Proceedings of the Nutrition Society. 2021;(1):59-64
Abstract
The preventability estimate for colorectal cancer (CRC) is approximately 50%, highlighting the huge potential for altering modifiable lifestyle factors (including diet and body fatness) in order to reduce risk of this common malignancy. There is strong evidence that dietary factors (including intake of wholegrains, fibre, red and processed meat and alcohol) affect CRC risk. The lack of positive intervention trials and limited mechanistic understanding likely explain limited public health impact of epidemiological observations, to date. An alternative strategy for nutritional prevention of CRC is use of supplements that provide higher individual nutrient exposure than obtained through the diet (chemoprevention). There are positive data for calcium and/or vitamin D and the n-3 fatty acid EPA from polyp prevention trials using colorectal adenoma as a CRC risk biomarker. Although CRC is an obesity-related malignancy, there remains a paucity of observational data supporting intentional weight loss for CRC risk reduction. Some types of obesity surgeries (Roux-en-Y gastric bypass) might actually increase subsequent CRC risk due to alteration of local intestinal factors. There is intense interest in nutritional therapy of patients after diagnosis of CRC, in order to impact on recurrence and overall survival (now often termed cancer interception). In conclusion, nutritional prevention of CRC continues to hold much promise. Increased mechanistic understanding of the role of individual nutrients (linked to intestinal microbiota), as well as a precision medicine approach to CRC chemoprevention and interception based on both tumour and host factors, should enable translation of nutritional interventions into effective CRC risk reduction measures.
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10.
Association of the microbiome with colorectal cancer development (Review).
Abdulla, MH, Agarwal, D, Singh, JK, Traiki, TB, Pandey, MK, Ahmad, R, Srivastava, SK
International journal of oncology. 2021;(5)
Abstract
Colorectal cancer (CRC) is the second most common malignancy causing cancer‑related mortality globally. It is the third most common type of cancer detected worldwide. The recent concept of the human body supporting a diverse community of microbes has revealed the important role these microbes play synergistically in maintaining normal homeostasis. The balance between the microbiomes and epithelial cells of the human body is essential for normal physiology. Evidence from meta‑genome analysis indicates that an imbalance in the microbiome is prominent in the guts of patients with CRC. Several studies have suggested that the gut microbiota can secrete metabolites [short‑chain fatty acids (SCFAs), vitamins, polyphenols and polyamines] that modulate the susceptibility of the colon and rectum by altering inflammation and DNA damage. The state of microbiome imbalance (dysbiosis) has been reported in patients with CRC, with an increasing population of 'bad' microbes and a decrease in 'good' microbes. The 'good' microbes, also known as commensal microbes, produce butyrate; however, 'bad' microbes cause a pro‑inflammatory state. The complex association between pathological microbial communities leading to cancer progression is not yet fully understood. An altered microbial metabolite profile plays a direct role in CRC metabolism. Furthermore, diet plays an essential role in the risk of gastrointestinal cancer development. High‑fiber diets regulate the gut microbiome and reduce the risk of CRC development, and may be fruitful in the better management of therapeutics. In the present review, the current status of the microbiome in CRC development is discussed.12.