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Colorectal (Bowel) Cancer

Colorectal cancer (or bowel cancer) is one of the most common types of cancer in both men and women. Approximately four fifths of these cancers are found in the colon (large intestine), and one fifth in the rectum. Prevention and early detection of colorectal cancer is important. Some of most common symptoms include a change in bowel habit (eg. constipation, and bleeding), mucus discharge, and discomfort or pain in the lower abdomen. The vast majority of colon and rectum cancers are adenocarcinomas, around 10% of these are mucinous (protein contained in mucus). The median age at diagnosis is 70, age adjusted incidence rates are slightly higher in males compared to females. A substantial proportion of cases are in those with a genetic predisposition to colorectal cancer. Diet may also have an influence on the incidence of colorectal cancer, diatry fibre, retinoids, and calcium are thought to be protective, while high intake of animal fats may increases risk. Colorectal cancer may develop from benign polyps (a polyp is a tumour on a stem most commonly found on mucous membranes). World-wide about 782,000 people are diagnosed with colorectal cancer each year.

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Latest Research Publications
Herdiatry Colorectal Cancers
Screening for Colorectal (Bowel) Cancer
Prevention of Colorectal (Bowel) Cancer

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  • PubMed search for publications about Colorectal Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Colorectal Cancer
    MeSH term: Colorectal Neoplasms
    International US National Library of Medicine
    qualityPubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.

Herdiatry Colorectal Cancers (5 links)

Between 15-20% of all colorectal cancers are thought to be familial. Some types of colon cancers and pre-disposing conditions are known to have an inherited element, in particular, Lynch Syndrome (hereditary non-polyposis colon cancer, HNPCC) and familial adenomatous polyposis (FAP).See also: Gene and Chromosome Abnormalities (Cancer GeneWeb)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Knudsen AB, Zauber AG, Rutter CM, et al.
Estimation of Benefits, Burden, and Harms of Colorectal Cancer Screening Strategies: Modeling Study for the US Preventive Services Task Force.
JAMA. 2016; 315(23):2595-609 [PubMed] Related Publications
IMPORTANCE: The US Preventive Services Task Force (USPSTF) is updating its 2008 colorectal cancer (CRC) screening recommendations.
OBJECTIVE: To inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden.
DESIGN, SETTING, AND PARTICIPANTS: Comparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis.
EXPOSURES: Screening with sensitive guaiac-based fecal occult blood testing, fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy with or without stool testing, computed tomographic colonography (CTC), or colonoscopy starting at age 45, 50, or 55 years and ending at age 75, 80, or 85 years. Screening intervals varied by modality. Full adherence for all strategies was assumed.
MAIN OUTCOMES AND MEASURES: Life-years gained compared with no screening (benefit), lifetime number of colonoscopies required (burden), lifetime number of colonoscopy complications (harms), and ratios of incremental burden and benefit (efficiency ratios) per 1000 40-year-olds.
RESULTS: The screening strategies provided LYG in the range of 152 to 313 per 1000 40-year-olds. Lifetime colonoscopy burden per 1000 persons ranged from fewer than 900 (FIT every 3 years from ages 55-75 years) to more than 7500 (colonoscopy screening every 5 years from ages 45-85 years). Harm from screening was at most 23 complications per 1000 persons screened. Strategies with screening beginning at age 50 years generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55 years. There were limited empirical data to support a start age of 45 years. For persons adequately screened up to age 75 years, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50 to 75 years, 4 strategies yielded a comparable balance of screening burden and similar LYG (median LYG per 1000 across the models): colonoscopy every 10 years (270 LYG); sigmoidoscopy every 10 years with annual FIT (256 LYG); CTC every 5 years (248 LYG); and annual FIT (244 LYG).
CONCLUSIONS AND RELEVANCE: In this microsimulation modeling study of a previously unscreened population undergoing CRC screening that assumed 100% adherence, the strategies of colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, and CTC every 5 years performed from ages 50 through 75 years provided similar LYG and a comparable balance of benefit and screening burden.

Lin JS, Piper MA, Perdue LA, et al.
Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
JAMA. 2016; 315(23):2576-94 [PubMed] Related Publications
IMPORTANCE: Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the United States.
OBJECTIVE: To systematically review the effectiveness, diagnostic accuracy, and harms of screening for CRC.
DATA SOURCES: Searches of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2008, through December 31, 2014, with surveillance through February 23, 2016.
STUDY SELECTION: English-language studies conducted in asymptomatic populations at general risk of CRC.
DATA EXTRACTION AND SYNTHESIS: Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted.
MAIN OUTCOMES AND MEASURES: Colorectal cancer incidence and mortality, test accuracy in detecting CRC or adenomas, and serious adverse events.
RESULTS: Four pragmatic randomized clinical trials (RCTs) evaluating 1-time or 2-time flexible sigmoidoscopy (n = 458,002) were associated with decreased CRC-specific mortality compared with no screening (incidence rate ratio, 0.73; 95% CI, 0.66-0.82). Five RCTs with multiple rounds of biennial screening with guaiac-based fecal occult blood testing (n = 419,966) showed reduced CRC-specific mortality (relative risk [RR], 0.91; 95% CI, 0.84-0.98, at 19.5 years to RR, 0.78; 95% CI, 0.65-0.93, at 30 years). Seven studies of computed tomographic colonography (CTC) with bowel preparation demonstrated per-person sensitivity and specificity to detect adenomas 6 mm and larger comparable with colonoscopy (sensitivity from 73% [95% CI, 58%-84%] to 98% [95% CI, 91%-100%]; specificity from 89% [95% CI, 84%-93%] to 91% [95% CI, 88%-93%]); variability and imprecision may be due to differences in study designs or CTC protocols. Sensitivity of colonoscopy to detect adenomas 6 mm or larger ranged from 75% (95% CI, 63%-84%) to 93% (95% CI, 88%-96%). On the basis of a single stool specimen, the most commonly evaluated families of fecal immunochemical tests (FITs) demonstrated good sensitivity (range, 73%-88%) and specificity (range, 90%-96%). One study (n = 9989) found that FIT plus stool DNA test had better sensitivity in detecting CRC than FIT alone (92%) but lower specificity (84%). Serious adverse events from colonoscopy in asymptomatic persons included perforations (4/10,000 procedures, 95% CI, 2-5 in 10,000) and major bleeds (8/10,000 procedures, 95% CI, 5-14 in 10,000). Computed tomographic colonography may have harms resulting from low-dose ionizing radiation exposure or identification of extracolonic findings.
CONCLUSIONS AND RELEVANCE: Colonoscopy, flexible sigmoidoscopy, CTC, and stool tests have differing levels of evidence to support their use, ability to detect cancer and precursor lesions, and risk of serious adverse events in average-risk adults. Although CRC screening has a large body of supporting evidence, additional research is still needed.

Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement.
JAMA. 2016; 315(23):2564-75 [PubMed] Related Publications
IMPORTANCE: Colorectal cancer is the second leading cause of cancer death in the United States. In 2016, an estimated 134,000 persons will be diagnosed with the disease, and about 49,000 will die from it. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years; the median age at death from colorectal cancer is 68 years.
OBJECTIVE: To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer.
EVIDENCE REVIEW: The USPSTF reviewed the evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy, computed tomography colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, the multitargeted stool DNA test, and the methylated SEPT9 DNA test in reducing the incidence of and mortality from colorectal cancer or all-cause mortality; the harms of these screening tests; and the test performance characteristics of these tests for detecting adenomatous polyps, advanced adenomas based on size, or both, as well as colorectal cancer. The USPSTF also commissioned a comparative modeling study to provide information on optimal starting and stopping ages and screening intervals across the different available screening methods.
FINDINGS: The USPSTF concludes with high certainty that screening for colorectal cancer in average-risk, asymptomatic adults aged 50 to 75 years is of substantial net benefit. Multiple screening strategies are available to choose from, with different levels of evidence to support their effectiveness, as well as unique advantages and limitations, although there are no empirical data to demonstrate that any of the reviewed strategies provide a greater net benefit. Screening for colorectal cancer is a substantially underused preventive health strategy in the United States.
CONCLUSIONS AND RECOMMENDATIONS: The USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years (A recommendation). The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patient's overall health and prior screening history (C recommendation).

Phongkitkarun S, Tohmad U, Larbcharoensub N, et al.
DCE-MRI-Derived Parameters as Predictors of Response to Neo-Adjuvant Chemoradiation Treatment of Rectal Carcinoma.
J Med Assoc Thai. 2016; 99(3):338-47 [PubMed] Related Publications
BACKGROUND: Preoperative combined chemoradiation treatment (CRT) is now accepted as the treatment of choice due to its benefits of decreasing the primary tumor volume and enhancing the sphincter preservation surgery. Determining whether a patient is responding to therapy is crucial for rectal cancer patients who may benefit from prompt treatment modifications.
OBJECTIVE: To evaluate the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the treatment response.
MATERIAL AND METHOD: Nineteen patients with histologically proven rectal adenocarcinoma who were candidates for neo-adjuvant CRT were prospectively included. All patients were examined by conventional and DCE-MRi at three time points (pre-, during-, and post-CRT). Surgical resection was performed after complete CRT. The pathological response and Dworak regression grade were assessed. All parameters were blindly analyzed.
RESULTS: The median pathologic response rate for all patients was 40%. Dworak regression grades of 0, 1, 2, 3, and 4 were found in 0.0%, 21.1%, 42.1%, 26.3%, and 10.5% of patients, respectively. The tumor thickness and length were 30% and 32.9% lower at during-CRT and 40.6% and 44.7% lower post-CRT and had moderate and fair negative correlations with the pathologic response rate and Dworak regression rate, respectively. Among the DCE-MRI parameters, only a change in the time to peak between pre- and during-CRT was correlated with the Dworak regression grade (p = 0.01). The percentage change in the time to peak in patients with poor regression (grades 0-1) was significantly greater than in patients with intermediate/complete regression (grades 2-4) [139.25% vs. 6.13%].
CONCLUSION: Changes in the tumor thickness and length evaluated by conventional MRI and the time to peak evaluated by DCE-MRI during CRT may be useful for predicting the treatment response of rectal cancer patients.

Octavian Neagoe C, Mazilu O
Pelvic intraoperative iatrogenic oncosurgical injuries: single-center experience.
J BUON. 2016 Mar-Apr; 21(2):498-504 [PubMed] Related Publications
PURPOSE: Iatrogenic events are more likely to occur during surgical treatment of malignant conditions. Gynecologic and colorectal cancers account for most of the cases that require surgical treatment within the pelvic area. The purpose of this study was to analyze the incidence of intraoperative accidents and the most frequently encountered injuries during surgery for cancers of the pelvic area.
METHODS: The records of 2702 patients admitted to our clinic over a 15-year period, (January 2000-December 2014), were analyzed for type and frequency of intraoperative accidents.
RESULTS: Urinary tract lesions were the most common injuries seen in this series (63.1%), followed by enteral (28.1%) and vascular (8.8%) injuries, with an overall incidence of 2.9% for the whole group. Iatrogenic injuries showed a statistically significant difference in incidence depending on the type of primary malignancy (p<0.002). Cervical cancer was associated with a higher rate of ureteral lesions, whereas enteral injuries occurred predominantly during surgical resection for ovarian cancer. The use of neoadjuvant radiotherapy or chemotherapy has been associated with a significantly lower risk of surgical iatrogenic injuries (p=0.004).
CONCLUSION: Immediate recognition of the lesion and prompt treatment are recommended in order to lower postoperative complications and to avoid a second operation.

Wu D, Li Q, Song G, Lu J
Identification of disrupted pathways in ulcerative colitis-related colorectal carcinoma by systematic tracking the dysregulated modules.
J BUON. 2016 Mar-Apr; 21(2):366-74 [PubMed] Related Publications
PURPOSE: The aim of this study was to identify the altered biological pathways associated with ulcerative colitis (UC)-related colorectal carcinoma (CRC) by systematic tracking the dysregulated modules from re-weighted protein- protein interaction (PPI) networks based on the expression profiles from normal, UC and various stages of CRC.
METHODS: We firstly recruited the UC- and CRC-related microarray data from ArrayExpress database, and obtained 8 expression profiles which contained 5 conditions (normal, UC, early stage CRC, stage II CRC and stage III CRC). Then, the PPI networks of normal and different disease stages were constructed and re-weighted using Pearson correlation coefficient (PCC). Next, the condition-specific modules were extracted from 5 PPI networks via clique-merging algorithm, and altered modules were captured on the basis of module correlation density (MCD). Subsequently, the gene compositions of altered modules and gene differential expressions in different disease stages were identified to screen the dysregulated genes. Finally, pathways enrichment analyses for the genes in altered modules and differentially expressed genes (DEGs) were implemented.
RESULTS: The extensive changes of gene correlations existed in 5 condition-specific PPI networks, which made different MCDs among different disease stages. The same number of modules (N=1952) were explored in 5 PPI networks. By comparing with normal condition, there were 463, 791, 1060 and 345 altered modules in UC, early stage CRC, stage II and III CRC, respectively. Overall, 77, 110, 170 and 110 common genes were identified between genes of altered modules and DEGs in UC, early stage CRC, stage II CRC and stage III CRC, respectively. Functional enrichment analyses indicated that cell cycle and oocyte meiosis were the common and most significant pathways in colonic diseases.
CONCLUSIONS: Tracking the altered modules from PPI networks is useful to uncover disrupted pathways in colonic diseases. Cell cycle and oocyte meiosis might be associated with the pathophysiological background of colonic diseases.

Tang SJ, Sones JQ
Colonoscopy Atlas of Colon Polyps and Neoplasms.
J Miss State Med Assoc. 2016; 57(3):68-71 [PubMed] Related Publications
Optical colonoscopy is the gold standard for colon cancer screening and adenoma detection and is the only screening option that can potentially provide therapeutic interventions and adenoma removal during the same session. When other screening strategies generate positive results, currently colonoscopy is the next step for definitive diagnosis and potentially curative therapy. For gastrointestinal endoscopists, the ileocecum is the finishing line during colonoscopy, and it is identified by three endoscopic landmarks: terminal ileum, ileocecal valve, and the appendiceal orifice. Careful and systematic examination should be stressed during endoscopic training and practice. In this pictorial review, the authors demonstrate common colon polyps and neoplasms that can be found during colonoscopy. Our aim is to educate gastroenterologists, endoscopy staff other health care providers, and interested patients on certain colon pathologies and common endoscopic interventions.

Duhé RJ
The Impact of Colorectal Cancer (CRC) in Mississippi, and the need for Mississippi to Eliminate its CRC Burden.
J Miss State Med Assoc. 2016; 57(3):62-7 [PubMed] Related Publications
Colorectal cancer (CRC), while highly preventable and highly treatable, is a major public health problem in Mississippi. This article reviews solutions to this problem, beginning with the relationship between modifiable behavioral risk factors and CRC incidence. It then describes the impact of CRC screening on national downward trends in CRC incidence and mortality and summarizes recent data on the burden of CRC in Mississippi. While other states have created Comprehensive Colorectal Cancer Control Programs in an organized effort to manage this public health problem, Mississippi has not. Responding to Mississippi's situation, the 70x2020 Colorectal Cancer Screening Initiative arose as an unconventional approach to increase CRC screening rates throughout the state. This article concludes by considering the current limits of CRC treatment success and proposes that improved clinical outcomes should result from research to translate recently-identified colorectal cancer subtype information into novel clinical paradigms for the treatment of early-stage colorectal cancer.

Filippi MK, Perdue DG, Hester C, et al.
J Cult Divers. 2016; 23(1):21-7 [PubMed] Related Publications
Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. Effective prevention and early detection may be achieved through screening, but screening rates are low, especially in American Indian (AI) populations. We wanted to understand perceptions of CRC screening among AI located in the Great Lakes region. Focus groups were recorded and transcribed verbatim (N = 45). Data were analyzed using qualitative text analysis. Themes that deterred CRC screening were low CRC knowledge, fear of the procedure and results, cost and transportation issues, and a lack of quality and competent care. Suggestions for improvement included outreach efforts and culturally-tailored teaching materials.

Rezapour S, Bahrami T, Hashemzadeh S, et al.
STC1 and NF-κB p65 (Rel A) is Constitutively Activated in Colorectal Cancer.
Clin Lab. 2016; 62(3):463-9 [PubMed] Related Publications
BACKGROUND: Stanniocalcin-1 (STC1) and nuclear factor (NF)-κB subunit p65 transcription factor are involved in various types of human malignancies. The roles of STC1 and NFκB-p65 in colorectal cancer (CRC) are still not fully understood. We investigated expression levels of NF-κB p65 and STC1 and also correlations between STC1 and NF-κB p65 expression and clinicopathological features in CRC.
METHODS: Tumor tissue samples were collected from 48 patients with CRC. RT-PCR and Real-time PCR analysis was performed to examine mRNA levels of STC1 and NF-κB p65.
RESULTS: The relative mRNA levels of STC1 and NF-κB p65 were significantly higher in tumor tissues than in adjacent mucosa (p = 0.025 and p = 0.044, respectively). The data also showed that STC1 and NF-κB p65 mRNA levels were not significantly associated with clinicopathological characteristics. In addition, there was no association between expression levels of STC1 and NF-κB p65 in tumor samples.
CONCLUSIONS: Our data indicate that STC1 and NF-κBp65 is activated constitutively in colorectal carcinoma tissues, suggesting that activation of these factors might play an important role in colorectal tumorigenesis. Future studies should examine STC1 and NF-κBp65 as a molecular target for the treatment of CRC.

Erdemli HK, Kocabas R, Salis O, et al.
Is Serum Caveolin-1 a Useful Biomarker for Progression in Patients with Colorectal Cancer?.
Clin Lab. 2016; 62(3):401-8 [PubMed] Related Publications
BACKGROUND: Colorectal cancer (CRC) is the third most common cause of cancer diagnosed in males and the second in females. Survival is strongly related to stage at diagnosis. There is an urgent need to find a noninvasive biomarker that can be commonly applied for screening diagnosis, early detection of recurrence, and monitoring of metastatic CRC. Protein caveolin-1 (CAV-1) has been known to be expressed abnormally in colon cancer and appears to contribute to aberrant signaling and protein trafficking. There are controversial results regarding the role of CAV-1 in cancer. We hypothesized that levels of CAV-1 in serum of patients with CRC might be important to estimate the progression of the disease. Therefore, the purpose of this study is to investigate whether serum CAV-1 might be used as a factor determining progression of CRC.
METHODS: A total of 61 patients with CRC (26 male, 35 female) and 46 controls (38 male, 8 female) were enrolled. Serum CAV-1 levels were measured by ELISA. The relationship between CAV-1 and progression-free survival (PFS) was analyzed with use of receiver operating characteristic (ROC) and Kaplan-Meier analysis. Results were given as median (95% CI). Mann-Whitney test was used for the comparison of groups.
RESULTS: CAV-1 levels were found to be 11.5 ng/mL (10.4-12.9) in CRC and 11.9 ng/mL (10.7-14.4) in controls (p = 0.465). The serum CAV-1 levels in CRC patients with disease progression and without progression were respectively 10.0 ng/mL (8.5-11.3) and 12.2 ng/mL (11.1-14.8) (p = 0.023). In ROC analysis, if CAV-1 levels are equal or lesser than 10.73 ng/mL, it might show presence of progression with a sensitivity 73.3% and specificity 66.7% in patients with CRC (area under the ROC curve (AUC) = 0.697, p = 0.005). The mean PFS time was found to be 29.7 months (19.8-39.7, 95% CI for the mean) in patients who have CAV-1 level ≤ 10.73 ng/mL and 61.9 months (44.2-79.6) in patients who have CAV-1 level > 10.73 ng/mL [hazard ratios (HR) with 95% CI = 3.49 (1.26 - 9.68) (p = 0.017)].
CONCLUSIONS: Our results strongly suggest that CAV-1 levels might be used as a marker to determine progression of CRC. When considered in combination with other biomarkers of CRC, CAV-1 is clinically informative and instructive.

Liu J, Zhou Q, Xu J, et al.
Detection of EGFR expression in patients with colorectal cancer and the therapeutic effect of cetuximab.
J BUON. 2016 Jan-Feb; 21(1):95-100 [PubMed] Related Publications
PURPOSE: This study was designed to detect the expression of epidermal growth factor receptor (EGFR) in tumor specimens of patients with colorectal cancer (CRC); moreover, the relationship between EGFR expression and clinical factors as well as prognosis were analyzed to provide a basis for individualized treatment of CRC.
METHODS: This study used paraffin-embedded tumor specimens of 70 CRC patients who were treated with cetuximab. Immunohistochemistry (IHC) was used to detect the expression of EGFR in CRC tumor specimens. The patient clinical features and treatment administered were recorded and then, the therapeutic effect of cetuximab was evaluated. Progression-free survival (PFS) and overall survival (OS) were assessed.
RESULTS: The positive expression rate of EGFR was 64% (45/70), while 18 patients had negative expression. Twenty-two cases had weak positive expression, 15 cases positive expression and another 15 strongly positive expression. Of 70 specimens, 27 (38.6%) had high EGFR expression belonging to 20 (50%) males and 7 (23%) females (p<0.05). However, age, Karnofsky performance status (KPS), tumor site, grade of differentiation and clinical stage showed no significant difference in relation to EGFR expression (p>0.05). No patient achieved complete remission (CR), 15 (21.4%) had partial remission (PR), 12 (17.1%) were in stable state (SD) and 40 (57.1%) patients had disease progression (PD). Disease control rate (DCR) was 39.02% (16/41) in the group with low EGFR expression and 48.28% (14/29) in the group with high EGFR expression (p>0.05).
CONCLUSION: EGFR expression in CRC tissue is correlated with patient gender. In the group with higher EGFR expression, the effectiveness of cetuximab was significantly higher than that in the low EGFR expression group, indicating correlation between the high expression of EGFR and the short-term effect of cetuximab.

Li QC, Liang Y, Tian Y, Hu GR
Arctigenin induces apoptosis in colon cancer cells through ROS/p38MAPK pathway.
J BUON. 2016 Jan-Feb; 21(1):87-94 [PubMed] Related Publications
PURPOSE: In the current study the antiproliferative effect of arctigenin, plant lignin, was evaluated on human colon cancer cell line HT-29. Furthermore, attempts were made to explore the signaling mechanism which may be responsible for its effect.
METHODS: Cell growth inhibition was assessed by MTT and LDH assays. Flow cytometric analysis was performed to determine cell arrest in the cell cycle phase and apoptosis. Furthermore, to confirm the apoptotic activity of arctigenin, caspase-9 and -3 activities analysis was performed. The levels of reactive oxygen species (ROS) and p38 mitogen activated protein kinase (MAPK) were investigated to determine their role in inducing apoptosis in arctigenin-treated HT-29 colon cancer cell line.
RESULTS: MTT and LDH results demonstrated significant cell growth inhibitory effect of arctigenin on HT-29 cells in a dose-dependent manner. Furthermore, increase in cell number arrested at G2/M phase was observed in flow cytometric analysis upon arctigenin treatment. In addition, arctigenin increased the apoptotic ratio in a dose-dependent manner. The involvement of intrinsic apoptotic pathway was indicated by the activation of caspase-9 and -3. Moreover, increased ROS production, activation of p38 MAPK and changes in mitochondrial membrane potential (ΔΨm) also revealed the role of intrinsic apoptotic signaling pathway in cell growth inhibition after arctigenin exposure.
CONCLUSION: Arctigenin induces apoptosis in HT-29 colon cancer cells by regulating ROS and p38 MAPK pathways.

Dong J, Wang W, Yu K, et al.
Outcomes of laparoscopic surgery for rectal cancer in elderly patients.
J BUON. 2016 Jan-Feb; 21(1):80-6 [PubMed] Related Publications
PURPOSE: Elderly patients with rectal cancer are regarded as being at increased risk during radical resection because of lack of functional reserve and increased number of comorbidities. The aim of this study was to compare the short- and long-term outcomes of laparoscopic surgery with radical intent between elderly and young rectal cancer patients.
METHODS: Three-hundred ten patients who underwent laparoscopic surgery with radical intent for rectal cancer at our institution between January 2008 and December 2014 were included in this retrospective study. Patients were divided into two age groups (younger than 70 years and older than 70 years) and were evaluated with respect to short- and long-term outcomes.
RESULTS: Postoperative morbidity was similar in elderly and young groups (p=0.718). Overall survival and disease-free survival were not significantly different between the two groups. Advanced age was not independent predictor of overall survival and disease-free survival by univariate and multivariate analysis.
CONCLUSION: Our data indicate that laparoscopic surgery with radical intent can be performed as safely in elderly patients as in young patients, with comparable postoperative results and long-term outcomes.

Pantelic A, Markovic M, Pavlovic M, Jancic S
Cetuximab in third-line therapy of patients with metastatic colorectal cancer: A single institution experience.
J BUON. 2016 Jan-Feb; 21(1):70-9 [PubMed] Related Publications
PURPOSE: Cetuximab, an IgG1 chimeric monoclonal antibody (MAB) against epidermal growth factor receptor (EGFR) has activity against metastatic colorectal cancers (mCRC) that express EGFR. The purpose of this study was to demonstrate the efficacy and safety of cetuximab administered to patients with EGFR-positive mCRC.
METHODS: 72 patients with wild-type KRAS mCRC were enrolled. All of them had previously been treated with a fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy. Patients received cetuximab as monotherapy or in combination with irinotecan-based chemotherapy. All patients were to be treated until the occurrence of disease progression or unacceptable toxicity.
RESULTS: All patients were evaluated for progression free survival (PFS), overall survival (OS) and safety. The median PFS was 4.77 months (95% CI: 4.08-5.45), with an actuarial 47.22% without progression at 3 months and 16.67% at 6 months. The median OS was 11.35 months (95% CI: 9.64-13.06), with 79.17% of the patients being alive at 6 months and 30.56% at 12 months. PFS was significantly higher in patients with skin toxicity as compared to those without skin toxicity (5.31 vs 2.61 months, p<0.001) and with smaller number of metastatic organs vs greater number of metastatic organs (p=0.05). OS was significantly higher in patients with good performance status (p=0.004), with skin toxicity (p=0.013) and with smaller number of metastatic organs (p<0.001). Superior survival rates with higher grades of skin toxicity were noticed. As for patient characteristics, there were no significant differences in age, gender, and primary site localization.
CONCLUSION: Cetuximab improved PFS, OS and preserved the quality of life in patients with mCRC whose previous treatments had failed.

Beyer KM, Zhou Y, Matthews K, et al.
Breast and Colorectal Cancer Survival Disparities in Southeastern Wisconsin.
WMJ. 2016; 115(1):17-21 [PubMed] Related Publications
BACKGROUND: Cancer health disparities by race, ethnicity, socioeconomic status, and geography are a top public health priority. Breast and colorectal cancer, in particular, have been shown to exhibit significant disparities and contribute a large proportion of morbidity and mortality from cancer. In addition, breast and colorectal cancer offer targets for prevention and control, including nutrition, physical activity, screening, and effective treatments to prolong and enhance the quality of survival. However, despite the investment of significant time and resources over many years, breast and colorectal cancer disparities persist, and in some cases, may be growing.
METHODS: This paper examines breast and colorectal cancer survival disparities in an 8-county region in southeastern Wisconsin, including the City of Milwaukee. Cox proportional hazards models were used to examine survival trends, and a new adaptation of adaptive spatial filtering--a disease mapping method--was used to examine spatial patterns of survival.
RESULTS: Disparities by race and ethnicity are revealed, and spatial analyses identify specific areas within the study region that have lower than expected survival rates.
CONCLUSIONS: Cancer control efforts in southeastern Wisconsin should focus on black/African American and Hispanic/Latina women to reduce breast cancer survival disparities, and black/African American populations to reduce colorectal cancer disparities. Evidence indicates that targeted interventions may be needed to serve populations in the Milwaukee and Kenosha metropolitan areas, as well as areas of Walworth, Ozaukee, and Waukesha counties.

Samadder NJ, Neklason DW, Boucher KM, et al.
Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial.
JAMA. 2016 Mar 22-29; 315(12):1266-75 [PubMed] Related Publications
IMPORTANCE: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful.
OBJECTIVE: To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP.
DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial, enrolling 92 participants with FAP, conducted from July 2010 through June 2014 at Huntsman Cancer Institute in Salt Lake City, Utah.
INTERVENTIONS: Participants with FAP were randomized to sulindac (150 mg) twice daily and erlotinib (75 mg) daily (n = 46) vs placebo (n = 46) for 6 months.
MAIN OUTCOMES AND MEASURES: The total number and diameter of polyps in the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden at 6 months. Polyp burden was calculated as the sum of the diameters of polyps. The secondary outcomes were change in total duodenal polyp count, change in duodenal polyp burden or count stratified by genotype and initial polyp burden, and percentage of change from baseline in duodenal polyp burden.
RESULTS: Ninety-two participants (mean age, 41 years [range, 24-55]; women, 56 [61%]) were randomized when the trial was stopped by the external data and safety monitoring board because the second preplanned interim analysis met the prespecified stopping rule for superiority. Grade 1 and 2 adverse events were more common in the sulindac-erlotinib group, with an acne-like rash observed in 87% of participants receiving treatment and 20% of participants receiving placebo (P < .001). Only 2 participants experienced grade 3 adverse events. [table: see text].
CONCLUSIONS AND RELEVANCE: Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after 6 months. Adverse events may limit the use of these medications at the doses used in this study. Further research is necessary to evaluate these preliminary findings in a larger study population with longer follow-up to determine whether the observed effects will result in improved clinical outcomes.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT 01187901.

Caviglia GP, Cabianca L, Fagoonee S, Gili FM
Colorectal cancer detection in an asymptomatic population: fecal immunochemical test for hemoglobin vs. fecal M2-type pyruvate kinase.
Biochem Med (Zagreb). 2016; 26(1):114-20 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Screening programs for colorectal cancer (CRC) are mainly based on a first-line fecal immunochemical test for hemoglobin (FIT). Fecal M2-type pyruvate kinase (M2-PK) has been evaluated in clinical settings showing promising results for early CRC detection. However, the impact of fecal M2-PK assessment on the performance of first-round CRC screening programs is not known. We investigated whether fecal M2-PK alone or in combination with FIT may improve CRC screening efficacy in the general population.
MATERIALS AND METHODS: A total of 1027 asymptomatic subjects (median age 66 [59-74] years; females 504 [49.1%]), identified through the general practitioners' rosters, were invited for the collection of 2 fecal samples for FIT and M2-PK evaluation. Participants with at least positive one fecal test were referred for colonoscopy. Quality indicators for screening performance were calculated and analyzed using Fisher's exact test.
RESULTS: Overall, 572 subjects underwent both FIT and M2-PK assessment (participation rate 55.7%): 93 participants showed positive results for at least one test (positivity rate 16.3%). Only 10 patients were positive for both tests. Attendance rate to colonoscopy was 86.0% and a total of 65 adenomas and 7 cancers were detected. Combined use of FIT and fecal M2-PK permitted the identification of 18 more neoplasm (25%) without improving colonoscopy workload, as deduced by the comparable number needed to scope (P = 0.402).
CONCLUSION: The addition of M2-PK testing to FIT offers the potential to detect additional neoplasms that either do not bleed or only bleed intermittently without reducing participation rate and without increasing endoscopy workload.

Swash C
Bariatric surgery and implications for stoma care.
Br J Nurs. 2016 Mar 10-23; 25(5):S22, S24-7 [PubMed] Related Publications
In the UK, 62% of the population are now described as being either overweight or obese. People with weight-management issues are more likely to suffer from cardiovascular disease and diabetes, as well as having an increased risk of cancer, including bowel cancer. Following the initial National Institute for Health and Care Excellence guidance in 2006, revised in 2014, health professionals have a more proactive role in identifying people with weight-management issues and supporting them to achieve a weight that helps reduce their health risks. This includes referrals to bariatric surgeons for consideration for surgery if appropriate. One particular surgical procedure, the Roux-en-Y, is not reversible and alters the capacity of the stomach and function of the small bowel in order to achieve weight loss. Using a case study, this article will highlight the role of the stoma nurse in managing a patient, who previously had a Roux-en-Y procedure for weight loss and subsequently needed formation of a loop ileostomy after surgery for bowel cancer.

Gao HL, Zhou N, Sun Z, et al.
KLF17 Expression in Colorectal Carcinoma and Its Clinical Significance.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2016; 38(1):69-72 [PubMed] Related Publications
OBJECTIVE: To detect KLF17 expression in colorectal carcinoma (CRC) and to evaluate its effect on the prognosis of colorectal carcinoma.
METHODS: Immunohistochemistry was performed to detect the expression of KLF17 in CRC and matched pericarcinous tissue,and the relationship between KLF17 expression and disease-free survival (DFS) was analyzed.
RESULTS: Of 73 CRC patients, KLF17 expression was positive in 32 patients and negative in 41 patients. KLF17 expression rate was significantly lower in CRC tissue than in pericarcinous tissue (χ(2)=12.418, P=0.001). The DFS of KLF17-positive stage III colon cancer patients was (56.3±7.2) months (95% CI: 42-70 months), which was significantly longer than that [(32.3±5.5) months (95% CI: 22-43 months)] of KLF17-negative patients (P=0.039).
CONCLUSION: KLF17 expression decreases in CRC tissue, and a positivie KLF17 expression predicts a better prognosis in stage III CRC patients.

De Angelis ML, Zeuner A, Policicchio E, et al.
Cancer Stem Cell-Based Models of Colorectal Cancer Reveal Molecular Determinants of Therapy Resistance.
Stem Cells Transl Med. 2016; 5(4):511-23 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
UNLABELLED: Colorectal cancer (CRC) therapy mainly relies on the use of conventional chemotherapeutic drugs combined, in a subset of patients, with epidermal growth factor receptor [EGFR]-targeting agents. Although CRC is considered a prototype of a cancer stem cell (CSC)-driven tumor, the effects of both conventional and targeted therapies on the CSC compartment are largely unknown. We have optimized a protocol for colorectal CSC isolation that allowed us to obtain CSC-enriched cultures from primary tumor specimens, with high efficiency. CSC isolation was followed by in vitro and in vivo validation, genetic characterization, and drug sensitivity analysis, thus generating panels of CSC lines with defined patterns of genetic mutations and therapy sensitivity. Colorectal CSC lines were polyclonal and maintained intratumor heterogeneity in terms of somatically acquired mutations and differentiation state. Such CSC-enriched cultures were used to investigate the effects of both conventional and targeted therapies on the CSC compartment in vivo and to generate a proteomic picture of signaling pathways implicated in sensitivity/resistance to anti-EGFR agents. We propose CSC lines as a sound preclinical framework to test the effects of therapies in vitro and in vivo and to identify novel determinants of therapy resistance.
SIGNIFICANCE: Colorectal cancer stem cells (CSCs) have been shown to be responsible for tumor propagation, metastatic dissemination, and relapse. However, molecular pathways present in CSCs, as well as mechanisms of therapy resistance, are mostly unknown. Taking advantage of genetically characterized CSC lines derived from colorectal tumors, this study provides an extensive analysis of CSC response to EGFR-targeted therapy in vivo and an overview of factors implicated in therapy response or resistance. Furthermore, the implementation of a biobank of molecularly annotated CSC lines provides an innovative resource for future investigations in colorectal cancer.

Onorati M, Uboldi P, Bianchi CL, et al.
Solitary thyroid metastasis from colon cancer: fine-needle aspiration cytology and molecular biology approach.
Pathologica. 2015 Sep-Dec; 107(3-4):192-6 [PubMed] Related Publications
Thyroid gland is one of the most vascularized organs of the body, nevertheless clinical and surgical series report an incidence of secondary malignancies in this gland of only 3%. Colorectal carcinoma metastatic to the thyroid gland is not as uncommon as previously believed, infact the number of cases seems to be increased in recent years due to the more frequent use of fine-needle aspiration cytology (FNAC) guided by ultrasonography. Although kidney, breast and lung metastases to the thyroid are frequent, metastasis from colon cancer is clinically rare with 52 cases reported in the literature in the last 5 decades and three cases described as solitary thyroid metastasis from the colon cancer without any other visceral metastases. To the best of our knowledge, we report the fourth case of solitary, asymptomatic thyroid metastasis from colon cancer without involvement of other organs. We discuss the importance of FNAC to detect metastatazing process as a compulsory step of the diagnostic and therapeutic management algorithm, combined with a molecular biology approach. A review of the last 5 decades literature, to update the number of cases described to date, is also included.

Jia M, Gao X, Zhang Y, et al.
Different definitions of CpG island methylator phenotype and outcomes of colorectal cancer: a systematic review.
Clin Epigenetics. 2016; 8:25 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
Contradictory results were reported for the prognostic role of CpG island methylator phenotype (CIMP) among colorectal cancer (CRC) patients. Differences in the definitions of CIMP were the most common explanation for these discrepancies. The aim of this systematic review was to give an overview of the published studies on CRC prognosis according to the different definitions of CIMP. A systematic literature search was performed in MEDLINE and ISI Web of Science for articles published until 3 April 2015. Data extraction included information about the study population, the definition of CIMP, and investigated outcomes. Thirty-six studies were included in this systematic review. Among them, 30 studies reported the association of CIMP and CRC prognosis and 11 studies reported the association of CIMP with survival after CRC therapy. Overall, 16 different definitions of CIMP were identified. The majority of studies reported a poorer prognosis for patients with CIMP-positive (CIMP+)/CIMP-high (CIMP-H) CRC than with CIMP-negative (CIMP-)/CIMP-low (CIMP-L) CRC. Inconsistent results or varying effect strengths could not be explained by different CIMP definitions used. No consistent variation in response to specific therapies according to CIMP status was found. Comparative analyses of different CIMP panels in the same large study populations are needed to further clarify the role of CIMP definitions and to find out how methylation information can best be used to predict CRC prognosis and response to specific CRC therapies.

Janevski V, Selmani R, Janevska V, et al.
Med Pregl. 2015 Nov-Dec; 68(11-12):413-7 [PubMed] Related Publications
INTRODUCTION: Gastrointestinal stromal tumors are the most common mesenchymal tumors of the digestive tract. Leiomyosarcomas of the gastrointestinal tract are rare mesenchymal neoplasms which grossly and histologically resemble gastrointestinal stromal tumors. They may be differentiated from gastrointestinal stromal tumors by using immunohistochemistry and they are typically positive for a smooth muscle actin and desmin and negative for c-kit, CD34 and DOG1.1. They often express calponin and h-caldesmon.
CASE REPORT: We present a case of a 59-year-old male with anemia, weight loss, intermittent abdominal pain and right abdominal mass. Colonoscopy revealed an exophytic ulcerated neoplastic mass in the ascending colon and abdominal computed tomography scan showed an ill-defined heterogeneous tumor mass which surrounded almost the whole ascending colon. The patient underwent right hemicolectomy and partial resection of ileum. Histopathological examination revealed a leiomyosarcoma composed of atypical spindle cells positive for a smooth muscle actin, desmin and vimentin, and negative for c-kit, CD34, S100 and neuron specific enolase. The patient is alive 8 months after the operation, undergoing chemotherapy.
CONCLUSION: We have concluded that the multimodal approach comprising chemotherapy and complete surgical resection controls the leiomyosarcomas.

Matovina E, Mihailović J, Nikoletić K, Srbovan D
Med Pregl. 2015 Nov-Dec; 68(11-12):376-81 [PubMed] Related Publications
INTRODUCTION: Early detection of recurrence is an important factor for long term survival of patients with colorectal cancer. Measurement of serum levels of carcinoembryonic antigen has been commonly used in the postoperative surveillance of colorectal cancer. The purpose of this study was to evaluate the ability of positron emission tomography-computed tomography to detect pathological substrate of elevated serum carcinoembryonic antigen in patients with colorectal cancer.
MATERIAL AND METHODS: The patients with colorectal cancer who underwent curative surgical resection and/ or chemotherapy, who were found in our database, were analyzed retrospectively. Forty-eight 18F-fluorodeoxyglucose positron emission tomography-computed tomography studies including 45 patients (14 women, 31 men; mean age: 62.93 years) with elevated serum, carcinoembryonic antigen levels, which had been performed between January 2011 and January 2014, were evaluated. Serum levels of carcinoembryonic antigen were measured within 3 months after positron emission tomography-computed tomography examination. Final diagnosis of recurrence was made by histopathological findings, radiology studies or clinical follow-up.
RESULTS: Recurrences were diagnosed in 37 patients, the prevalence being 77.1%. Liver metastases were found in 18 patients, abdominal, pelvic and/or mediastinal lymph nodes were positive in 19 patients, 11 patients had loco regional recurrences and 4 patients had pulmonary metastasis, and bone metastases were found in one patient. One patient was diagnosed with metastasis in scar tissue. The overall sensitivity and specificity of positron emission tomography-computed tomography was 90.24% and 71.42%, respectively. The positive and negative predictive values were 94.87% and 55.56%, respectively.
CONCLUSION: 18F-fluorodeoxyglucose positron emission tomography-computed tomography is a powerful tool that could be used in determining colorectal cancer recurrence in patients with elevated carcinoembryonic antigen levels and could have an important clinical impact on the management in patients with suspected recurrent colorectal cancer.

Beyaz S, Mana MD, Roper J, et al.
High-fat diet enhances stemness and tumorigenicity of intestinal progenitors.
Nature. 2016; 531(7592):53-8 [PubMed] Article available free on PMC after 03/09/2016 Related Publications
Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we show that high-fat diet (HFD)-induced obesity augments the numbers and function of Lgr5(+) intestinal stem cells of the mammalian intestine. Mechanistically, a HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-δ) signature in intestinal stem cells and progenitor cells (non-intestinal stem cells), and pharmacological activation of PPAR-δ recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-δ-dependent manner. Notably, HFD- and agonist-activated PPAR-δ signalling endow organoid-initiating capacity to progenitors, and enforced PPAR-δ signalling permits these progenitors to form in vivo tumours after loss of the tumour suppressor Apc. These findings highlight how diet-modulated PPAR-δ activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumours.

Jhaveri KS, Hosseini-Nik H, Thipphavong S, et al.
MRI Detection of Extramural Venous Invasion in Rectal Cancer: Correlation With Histopathology Using Elastin Stain.
AJR Am J Roentgenol. 2016; 206(4):747-55 [PubMed] Related Publications
OBJECTIVE: The purpose of this article is to evaluate the diagnostic performance of MRI for detection of extramural venous invasion (EMVI) compared with histopathologic analysis using elastin stain.
MATERIALS AND METHODS: Forty-nine patients with rectal cancer who had undergone surgical resection with preoperative MRI were identified. Thirty-seven patients had received preoperative chemoradiation therapy (CRT). Sixty-nine MRI studies were independently reviewed by two blinded radiologists for EMVI using a score of 0-4. Comparison was made with histopathologic results obtained by two pathologists reviewing the elastin-stained slides in consensus. EMVI status was also correlated with other tumoral and prognostic features on imaging and pathologic analysis. Statistical analysis was performed using Fisher exact and McNemar tests.
RESULTS: EMVI was present in 31% of the pathology specimens. An MRI EMVI score of 3-4 was 54% sensitive and 96% specific in detecting EMVI in veins 3 mm in diameter or larger. Inclusion of a score of 2 as positive for EMVI increased the sensitivity to 79% but decreased the specificity to 74%, with poor positive predictive value. Preoperative CRT had no significant effect on the diagnostic performance of MRI. Contrast-enhanced MRI increased reader confidence for diagnosis or exclusion of EMVI compared with T2-weighted imaging. EMVI status correlated with depth of extramural invasion and proximity to mesorectal fascia.
CONCLUSION: Despite an anticipated increase in sensitivity for EMVI detection by histopathologic analysis using elastin compared with H and E staining, MRI maintains a high specificity and moderate sensitivity for the detection of EMVI.

Vijay M, Sivagami G, Thayalan K, Nalini N
Radiosensitizing potential of rutin against human colon adenocarcinoma HT-29 cells.
Bratisl Lek Listy. 2016; 117(3):171-8 [PubMed] Related Publications
AIM: The present study was focused at evaluating the potential of rutin to improve the radiotherapeutic index and thereby the cytotoxicity towards colon cancer cells.
MATERIALS AND METHODS: HT-29 cells were pre-treated with rutin and the effect on cell proliferation was determined by MTT assay followed by exposure to radiation. After irradiation, experimental groups were sham control, rutin alone, radiation alone, rutin along with radiation-treated HT-29 cells.
RESULTS: Cytotoxicity study illustrated that treatment of HT-29 cells with different concentrations of rutin reduced cell proliferation in a dose- and time-dependent manner. After irradiation, the HT-29 cells revealed that the combined effect of 4 Gy radiation and rutin at 80 µM concentration showed a decrease in cell viability as compared to rutin‑alone treated and 4 Gy‑alone irradiated HT-29 cells. Furthermore, the increase in apoptotic cells, change from normal nuclei to abnormal nuclei, alterations in mitochondrial membrane potential, increase in DNA damage, increase in levels of lipid peroxidative markers, and decrease in antioxidant status were observed in 4 Gy‑ and rutin-treated group as compared to the other treated groups.
CONCLUSIONS: Combined effect of rutin and radiation in HT-29 cells leads to a more pronounced cell death rate. Thus, rutin exhibits radiosensitizing effects on HT-29 cells (Tab. 4, Fig. 8, Ref. 42).

Joseph DA, Redwood D, DeGroff A, Butler EL
Use of Evidence-Based Interventions to Address Disparities in Colorectal Cancer Screening.
MMWR Suppl. 2016; 65(1):21-8 [PubMed] Related Publications
Colorectal cancer (CRC) is the second leading cause of cancer death among cancers that affect both men and women. Despite strong evidence of their effectiveness, CRC screening tests are underused. Racial/ethnic minority groups, persons without insurance, those with lower educational attainment, and those with lower household income levels have lower rates of CRC screening. Since 2009, CDC's Colorectal Cancer Control Program (CRCCP) has supported state health departments and tribal organizations in implementing evidence-based interventions (EBIs) to increase use of CRC screening tests among their populations. This report highlights the successful implementation of EBIs to address disparities by two CRCCP grantees: the Alaska Native Tribal Health Consortium (ANTHC) and Washington State's Breast, Cervical, and Colon Health Program (BCCHP). ANTHC partnered with regional tribal health organizations in the Alaska Tribal Health System to implement provider and client reminders and use patient navigators to increase CRC screening rates among Alaska Native populations. BCCHP identified patient care coordinators in each clinic who coordinated staff training on CRC screening and integrated client and provider reminder systems. In both the Alaska and Washington programs, instituting provider reminder systems, client reminder systems, or both was facilitated by use of electronic health record systems. Using multicomponent interventions in a single clinical site or facility can support more organized screening programs and potentially result in greater increases in screening rates than relying on a single strategy. Organized screening systems have an explicit policy for screening, a defined target population, a team responsible for implementation of the screening program, and a quality assurance structure. Although CRC screening rates in the United States have increased steadily over the past decade, this increase has not been seen equally across all populations. Increasing the use of EBIs, such as those described in this report, in health care clinics and systems that serve populations with lower CRC screening rates could substantially increase CRC screening rates.

Ma Q, Chang Z, Wang W, Wang B
Rapamycin-Mediated mTOR Inhibition Reverses Drug Resistance to Adriamycin in Colon Cancer Cells.
Hepatogastroenterology. 2015; 62(140):880-6 [PubMed] Related Publications
BACKGROUND/AIMS: To detect the cellular sensitivity to adriamycin (ADR) by assessing autophagy, apoptosis, and multidrug resistance gene 1 (mdr1) expression in LoVo/Adr cells.
METHODOLOGY: LoVo/Adr cells were designated accordingly into ADR group, Rapamycin (RAPA) group, ADR plus RAPA, and control group in main observations. Autophage, cell death and mdr1 were examined.
RESULTS: IC50 value of ADR in LoVo/Adr was significantly decreased in response to RAPA (P < 0.05). Autophagy rate of LoVo/Adr cells was higher in the ADR or RAPA-alone group than in control (p < 0.05), while ADR/RAPA combination has significantly increased autophagy rate compared to ADR or RAPA alone (p < 0.05). Compared with controls, apoptosis rate in the RAPA group had no difference (p > 0.05); whereas there was significant difference in ADR group (p < 0.05). Furthermore, apoptosis rate was significantly different in combined RAPA/ADR compared to ADR (p < 0.05). Expression of mRNA and protein P-gp level of mdr 1 gene in LoVo/Adr cells were significantly decreased under RAPA-treated groups at 25 µmol/L and 50 µmol/L (p < 0.05).
CONCLUSION: This study has indicated that the inhibition of the mTOR pathway reverses multidrug resistance in colorectal cancer cells, which is associated with increased autophagy, apoptosis and reduced mdr1 gene expression in drug-resistant cells treated with Adriamycin.

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