Deficits in geriatric assessment are important in relation to fatigue in older patients with Inflammatory Bowel Disease.

Background: No previous study has investigated fatigue in older patients with Inflammatory Bowel Disease (IBD).

Aims: To describe the prevalence of fatigue in older patients and compare it to the prevalence in younger patients with IBD, and to determine factors associated with fatigue.

Methods: A prospective, multicenter cohort study, including older- (≥ 65 years) and younger patients with IBD (18-64 years).

Frailty Screening is Associated with Hospitalization and Decline in Quality of Life and Functional Status in Older Patients with Inflammatory Bowel Disease.

Background And Aims: Our goals were to study frailty screening in association with hospitalization and decline in quality of life [QoL] and functional status in older patients with inflammatory bowel diseases [IBD].

Methods: This was a prospective multicentre cohort study in IBD patients ≥65 years old using frailty screening [G8 Questionnaire]. Outcomes were all-cause, acute, and IBD-related hospitalization, any infection, any malignancy, QoL [EQ5D-3L], and functional decline (Instrumental Activities of Daily Living [IADL]) during 18 months of follow-up.

Statin use is associated with a reduced incidence of colorectal cancer expressing SMAD4.

Background: Long-term use of statins is associated with a small reduced risk of colorectal cancer but their mechanism of action is not well understood. While they are generally believed to act on KRAS, we have previously proposed that they act via influencing the BMP pathway. The objective of this study was to look for associations between statin use and the risk of developing colorectal cancer of a particular molecular subtype.

Deficits in Geriatric Assessment Associate With Disease Activity and Burden in Older Patients With Inflammatory Bowel Disease.

Background & Aims: We aimed to perform geriatric assessment in older patients with inflammatory bowel disease (IBD) to evaluate which IBD characteristics associate with deficits in geriatric assessment and the impact of deficits on disease burden (health-related quality of life).

Methods: A prospective multicenter cohort study including 405 consecutive outpatient patients with IBD aged ≥65 years. Somatic domain (comorbidity, polypharmacy, malnutrition), impairments in (instrumental) activities of daily living, physical capacity (handgrip strength, gait speed), and mental (depressive symptoms, cognitive impairment) and social domain (life-partner) were assessed.

Kinome-wide analysis of the effect of statins in colorectal cancer.

Background: Epidemiological studies and meta-analyses show an association between statin use and a reduced incidence of colorectal cancer (CRC). We have shown that statins act on CRC through bone morphogenetic protein (BMP) signalling, but the exact cellular targets and underlying mechanism of statin action remain elusive. In this study, we set out to assess the influence of statins on global cancer cell signalling by performing an array-based kinase assay using immobilised kinase substrates spanning the entire human kinome.

Patient Experiences and Outcomes of a Telehealth Clinical Care Pathway for Postoperative Inflammatory Bowel Disease Patients.

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Statin Use After Diagnosis of Colon Cancer and Patient Survival.

Background & Aims: Statin use has been associated with a reduced incidence of colorectal cancer and might also affect survival of patients diagnosed with colon cancer. Statins are believed to inhibit Ras signaling and may also activate the bone morphogenetic protein (BMP) signaling pathway in colorectal cancer cells. We investigated the effects of statins on overall survival of patients with a diagnosis of colon cancer, and whether their effects were associated with changes in KRAS or the BMP signaling pathways.

A Meta-Analysis of SMAD4 Immunohistochemistry as a Prognostic Marker in Colorectal Cancer.

Aim: SMAD4 immunohistochemistry is considered a valuable prognostic marker in colorectal cancer, but individual studies have often been small and the results variable. A meta-analysis could potentially clarify these findings.

Methods: In September 2014, a Pubmed and Google Scholar search was conducted to find publications that reported the prognostic value of SMAD4 expression.

Loss of SMAD4 alters BMP signaling to promote colorectal cancer cell metastasis via activation of Rho and ROCK.

Background & Aims: SMAD4 frequently is lost from colorectal cancers (CRCs), which is associated with the development of metastases and a poor prognosis. SMAD4 loss is believed to alter transforming growth factor β signaling to promote tumor progression. However, SMAD4 is also a central component of the bone morphogenetic protein (BMP) signaling pathway, implicated in CRC pathogenesis by human genetic studies.

Correction: Intestinal Tumorigenesis Is Not Affected by Progesterone Signaling in Rodent Models.

[This corrects the article DOI: 10.1371/journal.pone.

Evaluation of the prognostic value of pSMAD immunohistochemistry in colorectal cancer.

SMAD4 mutations and recent genome-wide association studies (GWAS) show the importance of bone morphogenetic protein (BMP) and transforming growth factor-β (TGF-β) signalling in the development of colorectal cancer (CRC). Loss of SMAD4 has been implicated as a predictive marker in CRC. As activation of the BMP and TGF-β pathways leads to phosphorylation of SMAD1,5,8 and SMAD2,3, respectively, and both need SMAD4 for translocation to the nucleus, we aimed to investigate whether nuclear staining of pSMAD1,5,8 and pSMAD2, 3 can be used as predictive markers in CRC.

Cholesterol metabolism and colorectal cancers.

Colorectal cancer (CRC) is primarily a lifestyle disease of the western world. As such it can be likened to cardiovascular disease and indeed it shares many of the same risk factors. It is therefore perhaps unsurprising that cholesterol metabolism and colorectal cancer are also intricately linked.

The activities of Smad and Gli mediated signalling pathways in high-grade conventional osteosarcoma.

High-grade conventional osteosarcoma is a malignant tumour predominantly affecting adolescents and, despite multimodal intensive therapy, lethal for one third of the patients. Although there is currently detailed knowledge of normal skeletal development, this has not been integrated into research on the genesis of osteosarcoma. Recently we showed that the canonical Wnt pathway is not active in osteosarcoma and that its reactivation is disadvantageous to osteosarcoma cells.

Intestinal tumorigenesis is not affected by progesterone signaling in rodent models.

Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR) is not expressed.

Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway.

Background: Promoter hypermethylation is an important and potentially reversible mechanism of tumour suppressor gene silencing in cancer. Compounds that demethylate tumour suppressor genes and induce differentiation of cancer cells, but do not have toxic side effects, would represent an exciting option in cancer therapy. Statins are cholesterol-lowering drugs with an excellent safety profile and associated with a reduced incidence of various cancers including colorectal cancer (CRC).

The potential of statins for individualized colorectal cancer chemoprevention.

Colorectal cancer is a leading cause of death by cancer in the western world. Despite major progress, even new chemotherapeutic regimens have had relatively little impact on long term survival in the approximately 50% of patients with advanced disease at presentation meaning that prevention is the only realistic way to reduce the burden of this disease. Many countries have implemented population-based screening methods to prevent colorectal cancer by the physical removal of its precursor lesion the adenoma, or to detect cancer at an earlier stage when it is amenable to surgical cure.

The role of EZH2 and DNA methylation in the silencing of the tumour suppressor RUNX3 in colorectal cancer.

In gastric cancer, a new epigenetic mechanism of tumour suppressor loss has been suggested where the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is responsible for loss of expression of RUNX3. This is consistent with EZH2 upregulation in multiple cancer types being associated with poor prognosis. We investigated whether EZH2 influences the expression of RUNX3 in colorectal cancer (CRC) and whether this is independent of methylation.