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Article ; Online: Dual role of autophagy in colon cancer cell survival.

Yang, Shi Yu / Winslet, Marc C

2011 Volume 18 Suppl 3, Page(s) S239

MeSH term(s)	Adenine/analogs & derivatives ; Antimetabolites, Antineoplastic/pharmacology ; Apoptosis/drug effects ; Autophagy/drug effects ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/pathology ; Fluorouracil/pharmacology ; Humans
Chemical Substances	Antimetabolites, Antineoplastic ; Adenine (JAC85A2161) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2011-12
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-011-1789-x
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Article ; Online: Ischemic preconditioning of small bowel mitigates the late phase of reperfusion injury: heme oxygenase mediates cytoprotection.

Mallick, Ismail H / Winslet, Marc C / Seifalian, Alexander M

American journal of surgery

2010 Volume 199, Issue 2, Page(s) 223–231

Abstract: 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 ... ...

Abstract	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). Mucosal perfusion and leukocyte-endothelial interactions were measured with the aid of an intravital microscope. At the end of the experiments, blood samples for lactate dehydrogenase (LDH) levels and biopsies of ileum for histologic evaluation were obtained. Results: IPC significantly improved the mucosal perfusion and decreased the leukocyte-endothelial interactions. Histologic examination showed that ileal mucosa was significantly less injured in the IPC and PDTC groups as compared with the IR group. Conclusions: IPC protects the intestine from late reperfusion injury. HO-1 is involved in this protection. These findings may be of significant importance in clinical small bowel transplantation.
MeSH term(s)	Animals ; Heme Oxygenase-1/metabolism ; Ileum/blood supply ; Ileum/enzymology ; Ileum/pathology ; Ileum/transplantation ; Intestinal Mucosa/blood supply ; Intestinal Mucosa/enzymology ; Intestinal Mucosa/pathology ; Ischemic Preconditioning ; Male ; Microcirculation ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/enzymology ; Reperfusion Injury/pathology ; Reperfusion Injury/prevention & control ; Short Bowel Syndrome/surgery
Chemical Substances	Heme Oxygenase-1 (EC 1.14.14.18)
Language	English
Publishing date	2010-02
Publishing country	United States
Document type	Evaluation Studies ; Journal Article
ZDB-ID	2953-1
ISSN	1879-1883 ; 0002-9610
ISSN (online)	1879-1883
ISSN	0002-9610
DOI	10.1016/j.amjsurg.2009.01.011
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Article: Tortuous common carotid artery as a cause of dysphagia.

Gupta, Ashish / Winslet, Marc C

Journal of the Royal Society of Medicine

2005 Volume 98, Issue 6, Page(s) 275–276

MeSH term(s)	Aged ; Aged, 80 and over ; Carotid Artery, Common/pathology ; Carotid Stenosis/complications ; Carotid Stenosis/pathology ; Deglutition Disorders/etiology ; Deglutition Disorders/pathology ; Esophageal Stenosis/etiology ; Esophageal Stenosis/pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Torsion Abnormality/complications ; Torsion Abnormality/pathology
Language	English
Publishing date	2005-06
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	6731-3
ISSN	1758-1095 ; 0141-0768 ; 0035-9157
ISSN (online)	1758-1095
ISSN	0141-0768 ; 0035-9157
DOI	10.1177/014107680509800611
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Article ; Online: Vascular complications of pancreatitis.

Mallick, Ismail H / Winslet, Marc C

JOP : Journal of the pancreas

2004 Volume 5, Issue 5, Page(s) 328–337

MeSH term(s)	Humans ; Pancreatitis/complications ; Vascular Diseases/etiology ; Vascular Diseases/mortality ; Vascular Diseases/therapy
Language	English
Publishing date	2004-09
Publishing country	Italy
Document type	Journal Article ; Review
ISSN	1590-8577
ISSN (online)	1590-8577
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Article: Az inzulinszeru növekedési faktor (IGF) szerepe a sejtosztódási folyamatokban és a daganatokban.

Vasas, Péter / Winslet, Marc C / Shi, Yu Yang

Orvosi hetilap

2009 Volume 150, Issue 51, Page(s) 2308–2312

Abstract: 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 ... ...

Title translation	The role of insulin-like growth factors (IGF) in cell division processes and in malignancy.
Abstract	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. The IGF binding proteins (IGFBP) modulate the bioavailability of IGFs. Upon ligand binding to the receptor, the intrinsic tyrosine kinase activity initiates the phosphatidylinositol-3-kinase (PI3-K) and p38 mitogen activated protein kinase (MAPK) pathway; these have a summon effect on cell cycle. The ligand and the receptor biosynthesis are reviewed, as well as the signal transduction system and the IGF' role in neoplasm. Finally, the therapeutic modalities are surveyed with the preclinical drug's main features.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Apoptosis ; Cell Division ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Insulin-Like Growth Factor Binding Proteins/metabolism ; MAP Kinase Signaling System/drug effects ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Protein-Tyrosine Kinases/metabolism ; Somatomedins/metabolism ; Up-Regulation/drug effects
Chemical Substances	Antineoplastic Agents ; Insulin-Like Growth Factor Binding Proteins ; Somatomedins ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2)
Language	Hungarian
Publishing date	2009-12-20
Publishing country	Hungary
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	123879-6
ISSN	1788-6120 ; 0030-6002
ISSN (online)	1788-6120
ISSN	0030-6002
DOI	10.1556/OH.2009.28733
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Article ; Online: The effect of consecutively larger doses of L-arginine on hepatic microcirculation and tissue oxygenation in hepatic steatosis.

Ijaz, Samia / Winslet, Marc C / Seifalian, Alexander M

Microvascular research

2009 Volume 78, Issue 2, Page(s) 206–211

Abstract: 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 ... ...

Abstract	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. Hepatic blood flow, microcirculation, tissue oxyhaemoglobin (HBO(2)) in response to consecutive intravenous bolus administrations of l-arginine (50 mg/kg, 100 mg/kg, 300 mg/kg and 500 mg/kg) or normal saline, were assessed. Results: Baseline hepatic arterial flows and hepatic microcirculation values were significantly lower in steatotic livers vs. control livers. L-arginine significantly improved hepatic arterial, portal venous blood flow, hepatic microcirculation and tissue oxygenation in both fatty and control livers. Conclusions: The administration of NO in cumulatively larger doses is effective at improving hepatic blood flow, microcirculation and hepatic tissue oxygenation in steatotic liver and these results could form the basis of further work into using NO as a therapeutic tool to reclaim moderately steatotic grafts for use in liver transplantation.
MeSH term(s)	Animals ; Dose-Response Relationship, Drug ; Fatty Liver/metabolism ; Fatty Liver/physiopathology ; Laser-Doppler Flowmetry ; Liver/blood supply ; Liver/drug effects ; Liver Circulation/physiology ; Male ; Microcirculation/physiology ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/metabolism ; Oxygen/metabolism ; Portal Vein/metabolism ; Portal Vein/physiopathology ; Rats ; Rats, Sprague-Dawley ; Regional Blood Flow
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; Oxygen (S88TT14065) ; NG-Nitroarginine Methyl Ester (V55S2QJN2X)
Language	English
Publishing date	2009-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80307-8
ISSN	1095-9319 ; 0026-2862
ISSN (online)	1095-9319
ISSN	0026-2862
DOI	10.1016/j.mvr.2009.06.008
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Article ; Online: Cyclooxygenase/lipoxygenase shunting lowers the anti-cancer effect of cyclooxygenase-2 inhibition in colorectal cancer cells

Ganesh Radhakrishnan / Marks Daniel JB / Sales Kevin / Winslet Marc C / Seifalian Alexander M

World Journal of Surgical Oncology, Vol 10, Iss 1, p

2012 Volume 200

Abstract: Abstract 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- ... ...

Abstract	Abstract 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. It has been postulated that this might result from the shunting of arachidonic acid metabolism to the 5-lipoxygenase (5-LOX) pathway. Cancer cell viability is promoted by 5-LOX through several mechanisms that are similar to those of cyclooxygenase-2 (COX-2). Expression of 5-LOX is upregulated in colorectal adenoma and cancer. The aim of this study was to investigate the shunting of arachidonic acid metabolism to the 5-LOX pathway by cyclooxygenase inhibition and to determine if this process antagonizes the anti-cancer effect in colorectal cancer cells. Methods Three colorectal cancer cell lines (HCA7, HT-29 & LoVo) expressing 5-LOX and different levels of COX-2 expression were used. The effects of aspirin (a non-selective COX inhibitor) and rofecoxib (COX-2 selective) on prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) secretion were quantified by ELISA. Proliferation and viability were studied by quantifying double-stranded DNA (dsDNA) content and metabolic activity. Apoptosis was determined by annexin V and propidium iodide staining using confocal microscopy, and caspase-3/7 activity by fluorescent substrate assay. Results COX inhibitors suppressed PGE 2 production but enhanced LTB 4 secretion in COX-2 expressing cell lines ( P <0.001). The level of COX-2 expression in colorectal cancer cells did not significantly influence the anti-proliferative and pro-apoptotic effects of COX inhibitors due to the shunting mechanism. Conclusions This study provides evidence of shunting between COX and 5-LOX pathways in the presence of unilateral inhibition, and may explain the conflicting anti-carcinogenic effects reported with use of COX inhibitors.
Keywords	Apoptosis ; Colorectal cancer ; Cyclooxygenase ; Eicosanoids ; Lipoxygenase ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	616
Language	English
Publishing date	2012-09-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Stem cells and cancer: an overview.

Sales, Kevin M / Winslet, Marc C / Seifalian, Alexander M

Stem cell reviews

2007 Volume 3, Issue 4, Page(s) 249–255

Abstract: Definite evidence of the importance of cancer stem cells in the progression of cancer has now come to light. Key markers of these cells have been identified in many solid tumours as well as leukaemias. Specific studies modelling the tumour induction of ... ...

Abstract	Definite evidence of the importance of cancer stem cells in the progression of cancer has now come to light. Key markers of these cells have been identified in many solid tumours as well as leukaemias. Specific studies modelling the tumour induction of specific cells isolated by surface antigens such as CD44 have demonstrated that these cells are not only present in tumours but that they are the key units in their tumourgenecity. These findings provide useful insight for disease progression, treatment and metastasis. The wide variety of proposed markers, and their similarity to endothelial progenitor cells found in angiogenesis, complicates these studies. Definite proof falls only in the induction of tumours in vivo. Here we review the developments in cancer stem cells and the markers that have been found for these cells.
MeSH term(s)	Adult Stem Cells/transplantation ; Animals ; Biomarkers, Tumor/metabolism ; Female ; Genetic Therapy/methods ; Humans ; Hyaluronan Receptors/metabolism ; Male ; Neoplasms/etiology ; Neoplasms/pathology ; Neoplasms/physiopathology ; Neoplasms/therapy ; Neoplastic Stem Cells/pathology ; Neoplastic Stem Cells/physiology
Chemical Substances	Biomarkers, Tumor ; Hyaluronan Receptors
Language	English
Publishing date	2007-10-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2213179-6
ISSN	1558-6804 ; 1550-8943
ISSN (online)	1558-6804
ISSN	1550-8943
DOI	10.1007/s12015-007-9002-0
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Article ; Online: The relationship between smoking and severe dysplastic disease in patients with Barrett's columnar-lined oesophagus.

Ramus, James R / Gatenby, Piers A C / Caygill, Christine P J / Watson, Anthony / Winslet, Marc C

European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)

2012 Volume 21, Issue 6, Page(s) 507–510

Abstract: 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 ... ...

Abstract	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. Analysis was performed with SPSS using logistic regression for calculation of odds ratios (ORs) for development of HGD/AC. Data on smoking habits were available in 956 (74.6%) patients. There was no significant difference between smokers and nonsmokers in mean age (P=0.877) or length of follow-up (P=0.359). There was a significant risk of HGD/AC in patients with any history of smoking compared with those who had never smoked (P<0.001, OR 2.81). Ex-smokers of 10 years or more remained at a significantly higher risk of HGD/AC compared with those who had never smoked (P=0.001, OR 3.37). Current smokers were not at a significantly higher risk of HGD/AC compared with ex-smokers (P=0.857) nor were those who smoked at least 20 a day compared with those who smoked fewer than 20 a day (P=0.632). In patients with CLO, smoking appears to be a significant risk factor for the development of severe dysplastic disease; however, we did not observe a dose-dependent effect of smoking on progression of disease.
MeSH term(s)	Adenocarcinoma/etiology ; Adenocarcinoma/pathology ; Barrett Esophagus/complications ; Barrett Esophagus/pathology ; Cohort Studies ; Disease Progression ; Esophageal Neoplasms/etiology ; Esophageal Neoplasms/pathology ; Esophagus/pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Precancerous Conditions/etiology ; Precancerous Conditions/pathology ; Prognosis ; Risk Factors ; Smoking/adverse effects
Language	English
Publishing date	2012-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1137033-6
ISSN	1473-5709 ; 0959-8278
ISSN (online)	1473-5709
ISSN	0959-8278
DOI	10.1097/CEJ.0b013e328350b06f
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Zs.A 3621: Show issues

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

Ganesh, Radhakrishnan / Marks, Daniel J B / Sales, Kevin / Winslet, Marc C / Seifalian, Alexander M

World journal of surgical oncology

2012 Volume 10, Page(s) 200

Abstract: 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 ...

Abstract	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. It has been postulated that this might result from the shunting of arachidonic acid metabolism to the 5-lipoxygenase (5-LOX) pathway. Cancer cell viability is promoted by 5-LOX through several mechanisms that are similar to those of cyclooxygenase-2 (COX-2). Expression of 5-LOX is upregulated in colorectal adenoma and cancer. The aim of this study was to investigate the shunting of arachidonic acid metabolism to the 5-LOX pathway by cyclooxygenase inhibition and to determine if this process antagonizes the anti-cancer effect in colorectal cancer cells. Methods: Three colorectal cancer cell lines (HCA7, HT-29 & LoVo) expressing 5-LOX and different levels of COX-2 expression were used. The effects of aspirin (a non-selective COX inhibitor) and rofecoxib (COX-2 selective) on prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) secretion were quantified by ELISA. Proliferation and viability were studied by quantifying double-stranded DNA (dsDNA) content and metabolic activity. Apoptosis was determined by annexin V and propidium iodide staining using confocal microscopy, and caspase-3/7 activity by fluorescent substrate assay. Results: COX inhibitors suppressed PGE2 production but enhanced LTB4 secretion in COX-2 expressing cell lines (P <0.001). The level of COX-2 expression in colorectal cancer cells did not significantly influence the anti-proliferative and pro-apoptotic effects of COX inhibitors due to the shunting mechanism. Conclusions: This study provides evidence of shunting between COX and 5-LOX pathways in the presence of unilateral inhibition, and may explain the conflicting anti-carcinogenic effects reported with use of COX inhibitors.
MeSH term(s)	Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Apoptosis/drug effects ; Arachidonate 5-Lipoxygenase/chemistry ; Arachidonate 5-Lipoxygenase/metabolism ; Arachidonic Acid/metabolism ; Blotting, Western ; Cell Proliferation/drug effects ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Cyclooxygenase 2/chemistry ; Cyclooxygenase 2/metabolism ; Cyclooxygenase 2 Inhibitors/pharmacology ; Dinoprostone/metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Leukotriene B4/metabolism ; Tumor Cells, Cultured
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Cyclooxygenase 2 Inhibitors ; Leukotriene B4 (1HGW4DR56D) ; Arachidonic Acid (27YG812J1I) ; Arachidonate 5-Lipoxygenase (EC 1.13.11.34) ; Cyclooxygenase 2 (EC 1.14.99.1) ; PTGS2 protein, human (EC 1.14.99.1) ; Dinoprostone (K7Q1JQR04M)
Language	English
Publishing date	2012-09-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2118383-1
ISSN	1477-7819 ; 1477-7819
ISSN (online)	1477-7819
ISSN	1477-7819
DOI	10.1186/1477-7819-10-200
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