• Physical fitness

• Male
• Humans
• Cardiorespiratory Fitness
• Prospective Studies
• Incidence
• Sweden/epidemiology
• Risk Factors
• Prostatic Neoplasms/epidemiology
• Exercise Test
• Physical Fitness

• Cancerfonden

• apoptosis
• autophagy
• cell cycle arrest
• fisetin

• Colorectal cancer
• Dietary support
• Health-related quality of life
• Obesity
• Overweight
• Psychological distress

• Colorectal Neoplasms
• Diet, Healthy
• Humans
• Obesity/epidemiology
• Overweight/epidemiology
• Psychological Distress
• Quality of Life
• Surveys and Questionnaires
• Survivors

Intestinal flora is an important component in the human body, which have been reported to be involved in the occurrence and development of colorectal cancer (CRC). Indeed, changes in the intestinal flora in CRC patients compared to those in control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis. In this review, we summarize the current knowledge on the potential links between the intestinal microbiota and CRC. We illustrated the mechanisms by which intestinal flora imbalance affects CRC, mainly focusing on inflammation, microbial metabolites, and specific bacteria species. In addition, we discuss how a diet exhibits a strong impact on microbial composition and provides risks for developing CRC. Finally, we describe the potential future directions that are based on intestinal microbiota manipulation for CRC diagnosis and treatment.

• colorectal cancer
• diet
• inflammation
• intestinal flora
• microbial metabolites

The present study demonstrated that the oral administration of nobiletin significantly inhibited lung carcinogenesis in mice, and these chemopreventive effects could be attributed to its metabolites that showed potent anti-cancer effects.

Colorectal cancer is the leading cause of cancer-related deaths in Saudi Arabia. Cancer has a multifactorial nature and can be described as a disease of altered gene expression. The profiling of gene expression has been used to identify cancer subtypes and to predict patients’ responsiveness. Telomere-associated proteins that regulate telomere biology are essential molecules in cancer development. Thus, the present study examined their contributions to colorectal cancer progression in Saudi patients.

The expression of hTERT, TRF1, TRF2, POT1, ATR, ATM, Chk1 and Chk2 were measured via real-time PCR in matched cancerous and adjacent tissues of CRC patients. The protein level of hTERT, TRF1, TRF2, ATR, ATM, Chk1 and Chk2 were measured using immunohistochemistry. A region of hTERT core promoter was sequenced via Sanger sequencing. Methylation of CTCF binding site was examined via methylation-specific PCR. Finally, the length of telomere was estimated using q-PCR.

Our results showed that POT1, ATR, Chk1 and Chk2 show increased expression in CRC relative to the adjacent mucosa. The expression levels of each gene were associated with clinicopathological characteristics of patients with CRC. There was a positive correlation between the age of the patients and hTERT expression. Regarding tumor site, telomere length, ATR, ATM and Chk1 were shown to be altered. No somatic mutation was detected in hTERT core promoter, and no differences in methylation patterns at CTCF binding site in the promoter between normal and cancer tissues.

Analysis of targeted genes expression in colorectal cancer based on the clinical variables revealed that tumor location and age could have a role in gene expression and telomere length variations and this could be taken under consideration during CRC diagnosis and therapy. Other epigenetic mechanisms could influence hTERT expression in cancers. Our findings warrant further validation through experiments involving a larger number of patients.

• Adult
• Aged
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• DNA Damage
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Intestinal Mucosa/metabolism
• Intestinal Mucosa/pathology
• Male
• Middle Aged
• Neoplasm Proteins/biosynthesis
• Neoplasm Proteins/genetics
• Telomere Homeostasis
• Telomere-Binding Proteins/biosynthesis
• Telomere-Binding Proteins/genetics

MicroRNAs (miRNAs), endogenous small noncoding RNAs (ncRNAs), play crucial roles in cancer development. Many studies have demonstrated that miRNAs can serve as diagnostic and therapeutic biomarkers for malignancies. Additionally, single nucleotide polymorphisms (SNPs) located in miRNA functional regions have been reported to be involved in cancer susceptibility. In this study, we investigated the associations between SNPs located in miRNA functional regions and colorectal cancer (CRC) susceptibility. We systematically screened all candidate miRNAs and their SNPs and then evaluated the relationships between the SNPs and CRC susceptibility in a Han Chinese population including 878 patients with CRC and 884 controls. Genotyping was performed by TaqMan assay. After comprehensively screening the miRNAs and SNPs, we elected to evaluate the association between SNP rs2682818 in miR‐618 and CRC susceptibility. We found that the AA and AC/AA genotypes of rs2682818 were associated with a decreased risk of CRC compared with the CC genotype (odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.37–0.79 for AA vs. CC in codominant model; OR = 0.82, 95% CI = 0.68–0.99 for AC/AA vs. CC in dominant model). However, we obtained no statically significant results in our subgroup analyses. SNP rs2682818 in miR‐618 has potential as a biomarker for individuals with high CRC susceptibility. Our findings need to be verified in studies including larger samples. Moreover, molecular functional studies of miR‐681 must be performed to confirm its relationship with CRC.

• SNP
• Colorectal cancer
• MiR-618
• susceptibility

• Aged
• Body Mass Index
• Female
• Humans
• Male
• Middle Aged
• Obesity/genetics
• Phenotype
• Polymorphism, Single Nucleotide
• Smoking/genetics

• R35 CA197449 NCI NIH HHS
• K07 CA172294 NCI NIH HHS
• P30 CA023108 NCI NIH HHS
• P30 DK020541 NIDDK NIH HHS
• R21 CA202529 NCI NIH HHS
• 001 World Health Organization
• UM1 CA167462 NCI NIH HHS
• National Cancer Institute

• esophageal cancer
• gastric atrophy
• gastric cancer
• one-carbon metabolism
• vitamin B12

• Aged
• Carcinoma, Squamous Cell/blood
• Carcinoma, Squamous Cell/epidemiology
• Carcinoma, Squamous Cell/pathology
• Case-Control Studies
• Dietary Supplements
• Esophageal Neoplasms/blood
• Esophageal Neoplasms/epidemiology
• Esophageal Neoplasms/pathology
• Esophageal Squamous Cell Carcinoma
• Finland/epidemiology
• Folic Acid/blood
• Homocysteine/blood
• Humans
• Male
• Middle Aged
• Prospective Studies
• Riboflavin/blood
• Stomach Neoplasms/blood
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/pathology
• Vitamin B 12/blood
• Vitamin B 12 Deficiency/blood
• Vitamin B 12 Deficiency/pathology
• alpha-Tocopherol/administration & dosage
• beta Carotene/administration & dosage

• HHSN261201500005C NCI NIH HHS
• Z99 CA999999 Intramural NIH HHS

Toll-like receptors (TLRs)/NF-κB activation stimulated by lipopolysaccharide (LPS) was associated with diverse biological response in colon cancer, but the underlying mechanism was largely unknown. In the current study, we reported cell proliferation was elevated in adenomatous polyposis coli (APC) mutated- and APC knockdown cell lines, while the proliferation was inhibited in APC wild-type cell lines. Besides, in vivo experiments showed that LPS promoted APC knockdown tumor growth while inhibited proliferation of APC wild type. Further study confirmed that activation of TLRs/NF-κB signaling pathway by LPS cross regulated with APC/GSK-3β/β-catenin pathway, which were depend on APC status of cell lines. Taken together, APC genotypes play a key role in LPS induced different colon cancer biological response by cross-regulating β-catenin and NF-κB, which may provide a novel strategy for carcinogenesis prevention.

• NF-κB
• adenomatous polyposis coli
• colon cancer
• β-catenin

Background. Colorectal cancer (CRC) is a growing public health concern with increasing rates in countries with previously known low incidence. This study determined pattern and distribution of CRC in Tanzania and identified hot spots in case distribution. Methods. A retrospective chart audit reviewed hospital registers and patient files from two national institutions. Descriptive statistics, Chi square (χ²) tests, and regression analyses were employed and augmented by data visualization to display risk variable differences. Results. CRC cases increased sixfold in the last decade in Tanzania. There was a 1.5% decrease in incidences levels of rectal cancer and 2% increase for colon cancer every year from 2005 to 2015. Nearly half of patients listed Dar es Salaam as their primary residence. CRC was equally distributed between males (50.06%) and females (49.94%), although gender likelihood of diagnosis type (i.e., rectal or colon) was significantly different (P = 0.027). More than 60% of patients were between 40 and 69 years. Conclusions. Age (P = 0.0183) and time (P = 0.004) but not gender (P = 0.0864) were significantly associated with rectal cancer in a retrospective study in Tanzania. Gender (P = 0.0405), age (P = 0.0015), and time (P = 0.0075) were all significantly associated with colon cancer in this study. This retrospective study found that colon cancer is more prevalent among males at a relatively younger age than rectal cancer. Further, our study showed that although more patients were diagnosed with rectal cancer, the trend has shown that colon cancer is increasing at a faster rate.

• Fournier's gangrene
• Gas gangrene
• Necrotizing fasciitis
• Nutrition
• Obesity paradox

• mortality
• pay-for-performance
• type 2 diabetes

• Adolescent
• Adult
• Aged
• Cohort Studies
• Diabetes Mellitus, Type 2/mortality
• Diabetes Mellitus, Type 2/therapy
• Female
• Humans
• Male
• Middle Aged
• Reimbursement, Incentive
• Retrospective Studies
• Taiwan/epidemiology
• Young Adult

• Advanced cancer
• Patient-generated index
• Patient-reported outcomes
• Personalized measure
• Psychometric properties
• Quality of life
• Validity

• Adult
• Aged
• Female
• Humans
• Male
• Middle Aged
• Neoplasms/therapy
• Outcome Assessment, Health Care
• Patient Reported Outcome Measures
• Psychometrics/methods
• Quality of Life/psychology
• Surveys and Questionnaires
• Young Adult

• AHS-2 Adventist Health Study-2
• Adventists
• BC breast cancer
• Breast cancer
• Dietary patterns
• ER oestrogen receptor
• HR hazard ratio
• PR progesterone receptor
• Vegetarians

• Calibration
• Cohort Studies
• Female
• Humans
• Incidence
• Male
• Middle Aged
• Multivariate Analysis
• Probability
• Proportional Hazards Models
• Reproducibility of Results
• Republic of Korea/epidemiology
• Risk Factors
• Stomach Neoplasms/epidemiology

The tumor microenvironment (TME) is complex and constantly evolving. This is due, in part, to the crosstalk between tumor cells and the multiple cell types that comprise the TME, which results in a heterogeneous population of tumor cells and TME cells. This review will focus on two stromal cell types, the cancer-associated adipocyte (CAA) and the cancer-associated fibroblast (CAF). In the clinic, the presence of CAAs and CAFs in the TME translates to poor prognosis in multiple tumor types. CAAs and CAFs have an activated phenotype and produce growth factors, inflammatory factors, cytokines, chemokines, extracellular matrix components, and proteases in an accelerated and aberrant fashion. Through this activated state, CAAs and CAFs remodel the TME, thereby driving all aspects of tumor progression, including tumor growth and survival, chemoresistance, tumor vascularization, tumor invasion, and tumor cell metastasis. Similarities in the tumor-promoting functions of CAAs and CAFs suggest that a multipronged therapeutic approach may be necessary to achieve maximal impact on disease. While CAAs and CAFs are thought to arise from tissues adjacent to the tumor, multiple alternative origins for CAAs and CAFs have recently been identified. Recent studies from our lab and others suggest that the hematopoietic stem cell, through the myeloid lineage, may serve as a progenitor for CAAs and CAFs. We hypothesize that the multiple origins of CAAs and CAFs may contribute to the heterogeneity seen in the TME. Thus, a better understanding of the origin of CAAs and CAFs, how this origin impacts their functions in the TME, and the temporal participation of uniquely originating TME cells may lead to novel or improved anti-tumor therapeutics.

• Hematopoietic stem cell
• Cancer associated adipocyte
• Mesenchymal stromal cell
• Tumor progression
• Cancer associated fibroblast
• Plasticity
• Metastasis
• Fibrocyte

• P30 CA138313 NCI NIH HHS
• R01 CA148772 NCI NIH HHS

It is estimated that 20% of all cancer cases are caused by obesity. Vitamin D is thought to be one of the mechanisms underlying this association. This review aims to summarise the evidence for the mediating effect of vitamin D on the link between obesity and cancer.

Three literature searches using PubMed and Embase were conducted to assess whether vitamin D plays an important role in the pathway between obesity and cancer: (1) obesity and cancer; (2) obesity and vitamin D; and (3) vitamin D and cancer. A systematic review was performed for (1) and (3), whereas a meta-analysis including random effects analyses was performed for (2).

(1) 32 meta-analyses on obesity and cancer were identified; the majority reported a positive association between obesity and risk of cancer. (2) Our meta-analysis included 12 original studies showing a pooled relative risk of 1.52 (95% CI: 1.33-1.73) for risk of vitamin D deficiency (<50 nmol/L) in obese people (body mass index >30 kg/m²). (3) 21 meta-analyses on circulating vitamin D levels and cancer risk were identified with different results for different types of cancer.

There is consistent evidence for a link between obesity and cancer as well as obesity and low vitamin D. However, it seems like the significance of the mediating role of vitamin D in the biological pathways linking obesity and cancer is low. There is a need for a study including all three components while dealing with bias related to dietary supplements and vitamin D receptor polymorphisms.

The online version of this article (doi:10.1186/1471-2407-14-712) contains supplementary material, which is available to authorized users.

• Adenoma/etiology
• Adenoma/pathology
• Alcohol Drinking/adverse effects
• Alcohol Drinking/epidemiology
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/pathology
• Dose-Response Relationship, Drug
• Ethanol/administration & dosage
• Ethanol/adverse effects
• Humans
• Models, Statistical
• Risk
• Risk Factors
• Sex Factors

Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon.

Eighty Sprague–Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation.

Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM.

The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities.

• Animals
• Dialysis
• Homocysteine/blood
• Homocysteine/metabolism
• Homocysteine/physiology
• Humans
• Hyperglycemia/blood
• Hyperglycemia/therapy
• Hyperhomocysteinemia/blood
• Hyperhomocysteinemia/therapy
• Kidney/physiopathology
• Kidney Failure, Chronic/blood
• Kidney Failure, Chronic/mortality
• Kidney Failure, Chronic/therapy
• Meta-Analysis as Topic
• Renal Dialysis

Epigenetic changes frequently occur in human colorectal cancer. Genomic global hypomethylation, gene promoter region hypermethylation, histone modifications, and alteration of miRNA patterns are major epigenetic changes in colorectal cancer. Loss of imprinting (LOI) is associated with colorectal neoplasia. Folate deficiency may cause colorectal Carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation. HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment. Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer. This review is mainly focused on DNA methylation, histone modification, and microRNA changes in colorectal cancer.

• Drug Discovery/methods
• Gene Expression Regulation, Neoplastic/genetics
• Humans
• Intracellular Signaling Peptides and Proteins/metabolism
• Neoplasms/metabolism
• Neoplasms/prevention & control
• Signal Transduction/physiology
• Transcription Factors/metabolism

• R01 CA077646 NCI NIH HHS