Cyclooxygenase/lipoxygenase shunting lowers the anti-cancer effect of cyclooxygenase-2 inhibition in colorectal cancer cells.

Background: Arachidonic acid metabolite, generated by cyclooxygenase (COX), is implicated in the colorectal cancer (CRC) pathogenesis. Inhibiting COX may therefore have anti-carcinogenic effects. Results from use of non-steroidal anti-inflammatory drugs inhibiting only COX have been conflicting.

The relationship between smoking and severe dysplastic disease in patients with Barrett's columnar-lined oesophagus.

The aim of this study was to examine the relationship between smoking and oesophageal high-grade dysplasia (HGD) or adenocarcinoma (AC) in a large cohort of patients with Barrett's columnar-lined oesophagus (CLO). A total of 1280 patients diagnosed with CLO and registered with the UK National Barrett's Oesophagus Registry were included. Data, including smoking habits, were collected from the patient's notes and development of HGD or AC noted.

Endothelin-1 stimulates colon cancer adjacent fibroblasts.

Endothelin-1 (ET-1) is produced by and stimulates colorectal cancer cells. Fibroblasts produce tumour stroma required for cancer development. We investigated whether ET-1 stimulated processes involved in tumour stroma production by colonic fibroblasts.

Pretreatment with insulin-like growth factor I protects skeletal muscle cells against oxidative damage via PI3K/Akt and ERK1/2 MAPK pathways.

Oxidative stress has an important role in the pathogenesis of many muscle diseases. The major contributors to oxidative stress in muscle tissue are reactive oxygen species such as oxygen ions, free radicals, and peroxides. Insulin-like growth factor I (IGF-I) has been shown to increase muscle mass and promote muscle cell proliferation, differentiation, and survival.

[The role of insulin-like growth factors (IGF) in cell division processes and in malignancy].

Extensive research is being carried out to identify the role of insulin-like growth factor (IGF) in cellular development and tumorigenesis. There is substantial experimental and clinical evidence now that IGF and the related signalling pathways have important roles in regulating cellular proliferation, promoting cellular differentiation and anti-apoptotic effect. Significant amount of IGF is produced locally by neoplastic tissue, which gets into the circulation and adds to the naturally liver-generated and circulating amount.

Growth factors enhance endothelial progenitor cell proliferation under high-glucose conditions.

Background: The purpose of this study was to investigate the impact of growth regulators, including growth hormone (GH), insulin-like growth factor 1 (IGF-1), and mechano growth factor (MGF), on endothelial progenitor cell (EPC) proliferation at different glucose concentrations.

Material/methods: EPCs were isolated and cultured from peripheral blood samples of healthy volunteers and immunocytochemically characterized after 7 days. The effects of glucose and growth regulators on EPC proliferation were determined with the Alamar Blue and Trypan Blue assays.

In vitro small intestinal epithelial cell growth on a nanocomposite polycaprolactone scaffold.

Tissue engineering of the small intestine remains experimental despite worldwide attempts to develop a functional substitute for short bowel syndrome. Most published studies have reported predominant use of PLLA (poly-L-lactide acid)/PGA (polyglycolic acid) copolymer as the scaffold material, and studies have been limited by in vivo experiments. This lack of progress has inspired a fresh perspective and provoked further investigation and development in this field of tissue engineering.

Aspirin is not chemoprotective for Barrett's adenocarcinoma of the oesophagus in multicentre cohort.

Barrett's columnar-lined oesophagus is the precursor lesion for oesophageal adenocarcinoma. The overall rate of progression to adenocarcinoma is 0.59% per annum.

The effect of consecutively larger doses of L-arginine on hepatic microcirculation and tissue oxygenation in hepatic steatosis.

Background: Impairment of hepatic microcirculation in fatty liver is thought to render it more susceptible to the effects of ischaemia-reperfusion injury as compared to non-fatty liver grafts. The present study aimed to investigate the effect of consecutively larger doses of L-arginine on the hepatic microcirculation and tissue oxygenation of fatty liver.

Methods: Sprague-Dawley rats (200-250 g) were fed a liquid ethanol diet to induce hepatic steatosis or a normal diet for 6 weeks.

Functional blocking of specific integrins inhibit colonic cancer migration.

For more effective oncological management of disseminated colorectal cancer, therapies must be devised that target the different individual stages of metastasis development. Recent work showed that integrin subunits alpha2, alpha6 and beta4 are involved in the colorectal cancer cell extravasation process. By means of Immunocytochemistry and Western blotting, it was shown that all three integrins are expressed not only in human colorectal cancer cells (HT29) but also in rat colonic cancer cells (DHDK12).

The in-vivo effect of pyrrolidine dithiocarbamate on hepatic parenchymal microcirculation and oxygenation of the rat liver.

Objective: Pyrrolidine dithiocarbamate has been shown to be a potent inducer of haemeoxygenase-1. This study investigated its in-vivo effects on systemic and hepatic microcirculatory perfusion.

Methods: Male Sprague-Dawley rats (n=12) were administered intravenously with pyrrolidine dithiocarbamate (10, 20 and 50 mg/kg body weight) or vehicle (0.

IGF-I activates caspases 3/7, 8 and 9 but does not induce cell death in colorectal cancer cells.

Background: Colorectal cancer is the third most common cancer in the western world. Chemotherapy is often ineffective to treat the advanced colorectal cancers due to the chemo-resistance. A major contributor to chemo-resistance is tumour-derived inhibition or avoidance of apoptosis.

Ischemic preconditioning of small bowel mitigates the late phase of reperfusion injury: heme oxygenase mediates cytoprotection.

Background: Ischemia and reperfusion (IR) injury of the intestine is a major cause of morbidity and mortality following small bowel transplantation. The current study evaluates the effect of ischemic preconditioning (IPC) on the intestinal microcirculation in the late phase of IR injury of the intestine.

Methods: Sixty rats were randomly allocated to 5 study groups (n = 12 per group): (1) sham, (2) IR (3) IPC, (4) pyrrolidine dithiocarbamate (PDTC) (HO-1 inducer), and (5) zinc protoporhyrin (ZnPP) (HO-1 inhibitor).

Apoptosis and colorectal cancer: implications for therapy.

Colorectal cancer (CRC) is characterized by the partial suppression of apoptosis, which in turn gives tumours a selective advantage for survival and can cause current chemotherapy approaches to be ineffective. Recent progress in understanding the mechanisms of apoptosis in colorectal carcinogenesis has provided potential new targets for therapy. Here, we review recent studies of the regulation of apoptosis and its role in CRC initiation and progression, and we discuss the relationship between chemoresistance and the suppression of apoptosis.

Are newly diagnosed columnar-lined oesophagus patients getting younger?

Objectives: The prevalence of columnar-lined oesophagus seems to have increased steadily in the past three decades in Europe and North America. Although the vast majority of columnar-lined oesophagus will not progress to malignancy, it is nevertheless important to identify the risk factors associated with this condition. This study investigates whether there has been a change, at diagnosis, in age of columnar-lined oesophagus patients between 1990 and 2005, or an increase in the number of patients aged less than 50 years.

Surveillance of Barrett's columnar-lined oesophagus in the UK: endoscopic intervals and frequency of detection of dysplasia.

Objectives: Endoscopic surveillance of patients with columnar-lined oesophagus (CLO) may identify those with early adenocarcinoma (AC). The benefits of surveillance are unproven and there is little evidence to support recommendations for precise endoscopic intervals. We sought to examine surveillance practice for CLO in the UK and the impact of endoscopic intervals on detection of dysplastic disease.

An in vivo rat model for early development of colorectal cancer metastasis to liver.

At diagnosis of colorectal cancer, approximately 25% of the patients have established colorectal liver metastasis. Optimal management of disseminated disease requires therapies targeting multiple stages in hepatic colorectal cancer metastasis development. To facilitate this, biologically accurate in vivo models are required.

Treatment modality and risk of development of dysplasia and adenocarcinoma in columnar-lined esophagus.

Columnar metaplasia is the precursor lesion for esophageal adenocarcinoma, resulting from prolonged gastroesophageal reflux. The influence of the efficacy of reflux control on the development of neoplastic change in columnar-lined esophagus is not established. This study compares the rate of development of dysplasia and adenocarcinoma in patients with columnar metaplasia of the esophagus between patients treated pharmacologically and those treated with antireflux surgery.

Principles and applications of gene therapy in colon cancer.

Colorectal cancer is one of the leading causes of mortality and morbidity. Mutations and aberration of some of the genes may lead to colon cancer. With advancing knowledge, more and more defective genes can be identified.

Clinical potential of quantum dots.

Advances in nanotechnology have led to the development of novel fluorescent probes called quantum dots. Quantum dots have revolutionalized the processes of tagging molecules within research settings and are improving sentinel lymph node mapping and identification in vivo studies. As the unique physical and chemical properties of these fluorescent probes are being unraveled, new potential methods of early cancer detection, rapid spread and therapeutic management, that is, photodynamic therapy are being explored.

Inducing apoptosis of human colon cancer cells by an IGF-I D domain analogue peptide.

Background: The resistance of tumour cells to apoptosis is a major contributor to the limited effectiveness of chemotherapies. Insulin-like growth factor I (IGF-I) has potential to protect cancer cells from variety of apoptotic challenges. This study was carried out to investigate the effect of a novel IGF-I receptor antagonist on apoptosis in colon cancer cells.

Integrins: a method of early intervention in the treatment of colorectal liver metastases.

The integrin family of cell surface receptors were principally thought to be involved in cell adhesion. Intense study has shown that these glycoproteins also regulate a diverse range of physiological processes. Inappropriate activation of integrins has been implicated in many pathological processes.

In vivo models for early development of colorectal liver metastasis.

In Europe, colorectal cancer is the second most prevalent form of cancer diagnosed. Globally each year, almost one million cases of colorectal cancer are registered and almost half a million deaths are attributed to this disease. This high mortality is associated with the development of liver metastases.