ABSTRACT
OBJECTIVE: To explore influences on post-diagnosis dietary decision-making in colorectal cancer survivors (CRC) for future intervention development. METHODS: Individual semi-structured interviews were conducted with 30 CRC survivors. All interviews were recorded and transcribed verbatim for grounded theory analysis. RESULTS: Most CRC survivors interviewed reported making both short- and long-term changes post-diagnosis, influenced by physical symptoms and personal beliefs: short-term treatment-driven changes to facilitate recovery, manage treatment side-effects and avoid disruption in treatment; short-term 'patient role' driven changes heavily influenced by family members and cultural beliefs; long-term changes driven by residual symptoms and illness beliefs, including cancer causal attributions and beliefs about preventing future recurrences. Traditional Chinese medicinal (TCM) beliefs were influential in both short- and long-term dietary decision-making, which may explain why survivors focused on specific food items rather than food patterns. CONCLUSION: While our findings suggested that the majority of CRC survivors made dietary changes post-diagnosis, their dietary pattern and motivation may change over the course of their illness trajectory. Also, the types of changes made are often not consistent with existing dietary recommendations. It is necessary to consider illness perception and cultural beliefs when delivering dietary care or developing interventions for this population.
Subject(s)
Asian People/psychology , Cancer Survivors/psychology , Colorectal Neoplasms/psychology , Diet , Aged , Aged, 80 and over , Attitude to Health , Colorectal Neoplasms/diagnosis , Decision Making , Feeding Behavior , Female , Hong Kong , Humans , Interviews as Topic , Male , Medicine, Chinese Traditional , Middle Aged , Motivation , Qualitative Research , Socioeconomic FactorsABSTRACT
BACKGROUND: In colorectal carcinoma (CRC), activation of the Raf/MEK/ERK signaling pathway is commonly observed. In addition, the commonly used 5FU-based chemotherapy in patients with metastatic CRC was found to enrich a subpopulation of CD26(+) cancer stem cells (CSCs). As activation of the Raf/MEK/ERK signaling pathway was also found in the CD26(+) CSCs and therefore, we hypothesized that an ATP-competitive pan-Raf inhibitor, Raf265, is effective in eliminating the cancer cells and the CD26(+) CSCs in CRC patients. METHODS: HT29 and HCT116 cells were treated with various concentrations of Raf265 to study the anti-proliferative and apoptotic effects of Raf265. Anti-tumor effect was also demonstrated using a xenograft model. Cells were also treated with Raf265 in combination with 5FU to demonstrate the anti-migratory and invasive effects by targeting on the CD26(+) CSCs and the anti-metastatic effect of the combined treatment was shown in an orthotopic CRC model. RESULTS: Raf265 was found to be highly effective in inhibiting cell proliferation and tumor growth through the inhibition of the RAF/MEK/ERK signaling pathway. In addition, anti-migratory and invasive effect was found with Raf265 treatment in combination with 5FU by targeting on the CD26(+) cells. Finally, the anti-tumor and anti-metastatic effect of Raf265 in combination with 5FU was also demonstrated. CONCLUSIONS: This preclinical study demonstrates the anti-tumor and anti-metastatic activity of Raf265 in CRC, providing the basis for exploiting its potential use and combination therapy with 5FU in the clinical treatment of CRC.
Subject(s)
Antineoplastic Agents/pharmacology , Colorectal Neoplasms/metabolism , Imidazoles/pharmacology , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Pyridines/pharmacology , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Self Renewal , Colorectal Neoplasms/pathology , Drug Evaluation, Preclinical , Extracellular Signal-Regulated MAP Kinases/metabolism , Fluorouracil/pharmacology , HCT116 Cells , HT29 Cells , Humans , Mice , Mitogen-Activated Protein Kinases/metabolism , Proto-Oncogene Proteins B-raf/metabolism , Signal Transduction/drug effectsABSTRACT
Recent evidence suggests that a subpopulation of cancer cells, cancer stem cells (CSCs), is responsible for tumor growth in colorectal cancer. However, the role of CSCs in colorectal cancer metastasis is unclear. Here, we identified a subpopulation of CD26(+) cells uniformly present in both the primary and metastatic tumors in colorectal cancer patients with liver metastasis. Furthermore, in patients without distant metastasis at the time of presentation, the presence of CD26(+) cells in their primary tumors predicted distant metastasis on follow-up. Isolated CD26(+) cells, but not CD26(-) cells, led to development of distant metastasis when injected into the mouse cecal wall. CD26(+) cells were also associated with enhanced invasiveness and chemoresistance. Our findings have uncovered a critical role of CSCs in metastatic progression of cancer. Furthermore, the ability to predict metastasis based on analysis of CSC subsets in the primary tumor may have important clinical implication as a selection criterion for adjuvant therapy.
Subject(s)
Biomarkers, Tumor/biosynthesis , Carcinoma/diagnosis , Colorectal Neoplasms/diagnosis , Dipeptidyl Peptidase 4/biosynthesis , Liver Neoplasms/diagnosis , Neoplastic Stem Cells/metabolism , Animals , Apoptosis/drug effects , Apoptosis/genetics , Biomarkers, Tumor/genetics , Carcinoma/drug therapy , Carcinoma/genetics , Carcinoma/metabolism , Carcinoma/physiopathology , Carcinoma/secondary , Cell Migration Assays , Cell Transformation, Neoplastic/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Colorectal Neoplasms/physiopathology , Dipeptidyl Peptidase 4/genetics , Disease Progression , Drug Resistance, Neoplasm/genetics , Fluorouracil/pharmacology , Follow-Up Studies , Gene Expression Profiling , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/physiopathology , Liver Neoplasms/secondary , Mice , Mice, SCID , Neoplasm Invasiveness/genetics , Neoplasm Transplantation , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/pathology , Organoplatinum Compounds/pharmacology , Oxaliplatin , Prognosis , RNA, Small Interfering/genetics , Tumor Burden/drug effects , Tumor Burden/genetics , Tumor Cells, CulturedABSTRACT
BACKGROUND: To review currently available evidence on the use of adjuvant therapy to reduce the formation of postoperative intra-abdominal adhesions. METHODS: A search on Pubmed and the Cochrane library was undertaken using the keywords "abdominal", "adhesion", "postoperative", "prevention" and "reduction". Only randomised controlled trials, prospective non-randomised controlled studies and review articles published in the English language between 1990 and 2006 were included. RESULTS: Two prospective non-randomised controlled studies and 18 randomised controlled trials were included in this review. Adjuvant therapies reviewed included pharmacological agents (streptokinase, recombinant tissue plasminogen activator, vitamin E antioxidant molecules), and mechanical barriers (hyaluronic acid barriers, oxidised regenerated cellulose barriers, nanofibrous barriers and collagen foils). Hyaluronate/carboxymethylcellulose-based bioresorbable membrane (Seprafilm) appeared to be the most efficacious in reducing adhesion formation as well as decreasing the incidence of adhesion obstruction requiring reoperation in clinical studies. Drawbacks to the use of Seprafilm include high cost and complications such as haemorrhage and poor wound healing. CONCLUSIONS: Only a limited number of adjuvant treatment methods are currently available for the reduction of postoperative adhesions. Seprafilm has been proven to be the efficacious method to reduce adhesions. Investigations into the novel therapies are showing promising results in experimental studies and clinical studies before their wider application.