-
1.
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.
-
2.
Discovery of common and rare genetic risk variants for colorectal cancer.
Huyghe, JR, Bien, SA, Harrison, TA, Kang, HM, Chen, S, Schmit, SL, Conti, DV, Qu, C, Jeon, J, Edlund, CK, et al
Nature genetics. 2019;(1):76-87
-
-
Free full text
-
Abstract
To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
-
3.
Food, microbiome and colorectal cancer.
Niederreiter, L, Adolph, TE, Tilg, H
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2018;(7):647-652
Abstract
You are what you eat. This adage has been confirmed by many studies demonstrating the high impact of nutrition on risk of cardiovascular diseases, many malignancies and other diseases. Dietary factors are of major relevance in the evolution of colorectal carcinoma. Various aspects are involved in colorectal carcinoma pathogenesis including genetics, lifestyle, age, chronic inflammation and others. It has only recently been recognized that the gut microbiota might reflect an important missing link in the interaction between diet and subsequent colorectal carcinoma development. Dietary factors are a major confounding factor affecting the composition of the intestinal microbiota. Several preclinical and clinical studies have recently suggested a role for the intestinal microbiota in potentially initiating and driving colorectal carcinoma. Therefore it is increasingly acknowledged that dietary factors might favor carcinogenesis via manipulation of the gut microbiota via potential outgrowth of certain bacterial populations, such as Fusobacterium nucleatum, Escherichia coli or Bacteroides fragilis. Excitingly, recent large clinical studies also highlighted a role for the gut microbiota and in particular Akkermansia muciniphila in tumor response toward chemotherapeutic agents and immune checkpoint inhibitors. This review will concentrate on the role of dietary factors in affecting the microbiota and implications in colorectal carcinoma.
-
4.
Gut microbiota and colorectal cancer: insights into pathogenesis for novel therapeutic strategies.
Kang, Y, Pan, W, Cai, Y
Zeitschrift fur Gastroenterologie. 2017;(9):872-880
Abstract
Colorectal cancer (CRC), as a leading cause of cancer-related death, is triggered by the complex interplay of host genetics and environmental factors. Mounting evidence has shed light on the association of the gut microbiota dysbiosis with CRC. In CRC experimental models, certain gut microbial strains have been shown to inhibit or attenuate immune responses, indicating that specific species among intestinal commensal bacteria may play either a pathogenic or a protective role in the development of CRC. Oral intake of probiotics/prebiotics can therefore serve as a therapeutic approach for CRC treatment. Microbiota studies in cancer, however, are still at the early stage, lack of quantitative data for clinic application. Fortunately, sequencing-based technologies are a boon to further investigation on the association of the intestinal bacterial flora and human diseases. This review considers the evidence for the role of the gut microbiota in CRC development and progression, responsiveness to immune system, and the related therapeutic applications of probiotics/prebiotics.
-
5.
[Early versus traditional postoperative oral feeding in patients undergoing elective colorectal surgery: a meta-analysis of safety and efficacy].
Zhang, K, Cheng, S, Zhu, Q, Han, Z
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery. 2017;(9):1060-1066
Abstract
OBJECTIVE To compare the outcomes of early oral feeding (EOF) and the traditional oral feeding (TOF) in postoperative patients with colorectal cancer using Meta-analysis. METHODS The databases of PubMed, SCI, Ovid, The Cochrane Library, CNKI, CBM, VIP and Wanfang Data were searched to collect randomized controlled trial (RCT) about EOF versus TOF in patients undergoing elective colorectal surgery. The retrieval time span was from inception to June 1, 2016. The studies were screened according to the inclusion and exclusion criteria. The data were extracted and the quality was evaluated by 2 reviewers independently. The Meta-analysis was conducted using RevMan 5.2 software. RESULTS A total of 14 studies with 1 807 patients (906 cases in EOF group and 901 cases in TOF group) were included. The time to first passage of flatus (MD=-16.11 h, 95%CI:-18.27 to -13.94 h, P=0.00), postoperative hospital stay (MD=-1.92 d, 95%CI:-2.83 to -1.01 d, P=0.00), hospitalization cost (ten thousand yuan) (MD=-0.58, 95%CI:-0.71 to -0.46, P=0.00) were less in EOF group compared to TOF group. EOF patients had lower total complication rate (OR=0.68, 95%CI:0.48 to 0.95, P=0.03), in which the pulmonary infection (OR=0.27, 95%CI:0.13 to 0.53, P=0.00), pharyngolaryngitis (OR=0.06, 95%CI:0.04 to 0.11, P=0.00) were lower than those in TOF group, while the tube reinsertion (OR=2.34, 95%CI:1.08 to 5.07, P=0.03) was higher. The incidence of anastomotic leakage, nausea, vomiting, abdominal distension, diarrhea, and wound infection between two groups was not significantly different(all P>0.05). There was no significant difference between two groups in IgM (P>0.05), while the IgA (MD=0.3, 95%CI:0.12 to 0.48, P=0.00), IgG (MD=2.13 ,95%CI:0.82 to 3.44, P=0.001), CD4+ (MD=3.80, 95%CI:2.55 to 5.04, P=0.00), CD4+/CD8+ (MD=0.22, 95%CI:0.04 to 0.41, P=0.02) in EOF group were higher than those in TOF group. Postoperative CRP decreased rapidly in EOF group (MD=-30.10, 95%CI:-48.07 to -12.13, P=0.00), and IL-6 was not significantly different (P>0.05). EOF patients had higher serum albumin level 5 days after operation (MD=3.27, 95%CI: 2.48 to 4.07, P=0.00). CONCLUSIONS EOF can promote gas passage and defecation, reduce postoperative hospital stay and treatment costs. Also, it can decrease the incidence of complications and postoperative inflammation, and maintain immune function.
-
6.
Nanoscale Photodynamic Agents for Colorectal Cancer Treatment: A Review.
Yang, L, He, J, Wen, Y, Yi, W, Li, Q, Lin, L, Miao, X, Chen, W, Xiong, L
Journal of biomedical nanotechnology. 2016;(7):1348-73
Abstract
Colorectal cancer is the most common form of gastroenteric cancer worldwide. Photodynamic therapy is emerging as an attractive method to treat cancers. Candidate targets of photodynamic therapy include epidermal growth factor receptors, cholesterol and low-density lipoprotein, estrogen receptors, the nucleus and DNA, folic acid receptors, cholecystokinin A receptors, lectin saccharide receptors, and tumor-specific antibodies. Specifically, in colorectal tumors, anti-DR5 antibody and cancer-specific antibody moieties are involved. Cancer cells incorporate greater quantities of sugars, and glycoconjugated photosensitizer has remarkable internalization and cytotoxicity in colon/colorectal cancer cells. Simultaneously, to circumvent the bio-distribution limitation, other molecules, including lectins, Hyaluronic acid, and peptides, have also been considered for colorectal cancer. Other novel strategies indirectly targeting colorectal cancer include pH-responsive PS, enzymatically activated photosensitization, and cancer-suppressing immune cells, mainly macrophages. Recently, nanoparticles have gained attention as a versatile platform for multi-functional photodynamic therapy. In this review, we summarize the targeting strategies investigated and highlight the potential of nanoparticles for target photodynamic therapy in colorectal cancer.
-
7.
Probiotics, prebiotics and colorectal cancer prevention.
Ambalam, P, Raman, M, Purama, RK, Doble, M
Best practice & research. Clinical gastroenterology. 2016;(1):119-31
Abstract
Colorectal cancer (CRC), the third major cause of mortality among various cancer types in United States, has been increasing in developing countries due to varying diet and dietary habits and occupational hazards. Recent evidences showed that composition of gut microbiota could be associated with the development of CRC and other gut dysbiosis. Modulation of gut microbiota by probiotics and prebiotics, either alone or in combination could positively influence the cross-talk between immune system and microbiota, would be beneficial in preventing inflammation and CRC. In this review, role of probiotics and prebiotics in the prevention of CRC has been discussed. Various epidemiological and experimental studies, specifically gut microbiome research has effectively improved the understanding about the role of probiotics and microbial treatment as anticarcinogenic agents. A few human studies support the beneficial effect of probiotics and prebiotics; hence, comprehensive understanding is urgent to realize the clinical applications of probiotics and prebiotics in CRC prevention.
-
8.
Perioperative immunonutrition in normo-nourished patients undergoing laparoscopic colorectal resection.
Moya, P, Miranda, E, Soriano-Irigaray, L, Arroyo, A, Aguilar, MD, Bellón, M, Muñoz, JL, Candela, F, Calpena, R
Surgical endoscopy. 2016;(11):4946-4953
Abstract
OBJECTIVE To determine whether the joint implementation of immunonutrition and a laparoscopic approach improves morbidity, mortality, and length of stay (LOS) compared with dietary advice. BACKGROUND Despite progress in recent years in the surgical management of patients with colorectal cancer, postoperative complications are frequent. Nutritional supplements enriched with immunonutrients have recently been introduced into clinical practice. However, the immunonutrition benefits in patients undergoing colorectal laparoscopic surgery are unknown. METHODS This study was a prospective, randomized trial with two parallel treatment groups receiving an immune-enhancing dietary supplement for 7 days before colorectal resection and 5 days postoperatively or dietary advice. RESULTS A total of 128 patients were randomized. At baseline, both groups were comparable with respect to age, sex, surgical risk, comorbidities, and analytical and nutritional parameters. The median postoperative LOS was 5 days and was not significantly different between the groups. Wound infection differed significantly between the groups (11.50 vs. 0.00 %, p = 0.006). No other differences between the groups were identified. CONCLUSIONS The joint use of laparoscopy and supplementation with immunonutrients reduces surgical wound infection in patients undergoing colorectal surgery. TRIAL REGISTRATION This study is registered with ClinicalTrial.gov : NCT0239396.
-
9.
Perioperative Standard Oral Nutrition Supplements Versus Immunonutrition in Patients Undergoing Colorectal Resection in an Enhanced Recovery (ERAS) Protocol: A Multicenter Randomized Clinical Trial (SONVI Study).
Moya, P, Soriano-Irigaray, L, Ramirez, JM, Garcea, A, Blasco, O, Blanco, FJ, Brugiotti, C, Miranda, E, Arroyo, A
Medicine. 2016;(21):e3704
-
-
Free full text
-
Abstract
To compare immunonutrition versus standard high calorie nutrition in patients undergoing elective colorectal resection within an Enhanced Recovery After Surgery (ERAS) program.Despite progress in recent years in the surgical management of patients with colorectal cancer (ERAS programs), postoperative complications are frequent. Nutritional supplements enriched with immunonutrients have recently been introduced into clinical practice. However, the extent to which the combination of ERAS protocols and immunonutrition benefits patients undergoing colorectal cancer surgery is unknown.The SONVI study is a prospective, multicenter, randomized trial with 2 parallel treatment groups receiving either the study product (an immune-enhancing feed) or the control supplement (a hypercaloric hypernitrogenous supplement) for 7 days before colorectal resection and 5 days postoperatively.A total of 264 patients were randomized. At baseline, both groups were comparable in regards to age, sex, surgical risk, comorbidity, and analytical and nutritional parameters. The median length of the postoperative hospital stay was 5 days with no differences between the groups. A decrease in the total number of complications was observed in the immunonutrition group compared with the control group, primarily due to a significant decrease in infectious complications (23.8% vs. 10.7%, P = 0.0007). Of the infectious complications, wound infection differed significantly between the groups (16.4% vs. 5.7%, P = 0.0008). Other infectious complications were lower in the immunonutrition group but were not statistically significantly different.The implementation of ERAS protocols including immunonutrient-enriched supplements reduces the complications of patients undergoing colorectal resection.This study is registered with ClinicalTrial.gov: NCT02393976.
-
10.
Immunotherapy in colorectal cancer: What have we learned so far?
Sanchez-Castañón, M, Er, TK, Bujanda, L, Herreros-Villanueva, M
Clinica chimica acta; international journal of clinical chemistry. 2016;:78-87
Abstract
After decades of progress based on chemotherapy and targeted agents, patients with metastatic colorectal cancer still have low long-term survival, with more than 500,000 deaths occurring worldwide every year. Recent results showing clinical evidence of efficacy using immunotherapy in other types of tumors, such as melanoma and lung cancer, have also made this a viable therapy for evaluation in colorectal cancer in clinical trials. The development of cancer immunotherapies is progressing quickly, with a variety of technological approaches. This review summarizes the current status of clinical trials testing immunotherapy in colorectal cancer and discusses what has been learned based on previous results. Immunotherapy strategies, such as various models of vaccines, effector-cell therapy and checkpoint inhibitor antibodies, provide protection against progression for a limited subset of patients diagnosed with colorectal cancer. A better understanding of particular immune cell types and pathways in each patient is still needed. These findings will enable the development of novel biomarkers to select the appropriate subset of patients to be treated with a particular immunotherapy, and the tendencies determined from recent results can guide clinical practice for oncologists in this new therapeutic area and in the design of the next round of clinical trials.