The expression and prognostic impact of CXC-chemokines in stage II and III colorectal cancer epithelial and stromal tissue

Oladipo, O.; Conlon, Susan; O’Grady, Anthony; Purcell, Colin; Wilson, Catherine; Maxwell, Pamela; Johnston, Patrick G.; Stevenson, Michael; Kay, Elaine W.; Wilson, Richard H.; Waugh, David J.

doi:10.1038/sj.bjc.6606055

Cited by 71 publications

(64 citation statements)

References 43 publications

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“…In addition to the previously identified 47 integrin-MADCAM1 axis, this study revealed a number of interesting targets for antiadhesion therapy, including PECAM1, CXCL8, and CCL20, suggesting that anti-TNF-α therapy may work, at least in part, by downregulating certain CAMs [179] . Upregulation of CXCL1, CXCR1 and CXCR2 was reported by Oladipo et al [180] in tumor epithelium compared to normal adjacent tissue collected from patients with stage Ⅱ and Ⅲ CRC. In their analysis, no overall association between CXCL1, CXCR1 or CXCR2 expression and prognostic endpoints was found, although survival analysis demonstrated an inverse association between CXCL1 and recurrence-free survival in stage Ⅲ patients.…”

Section: Small and Large Intestinementioning

confidence: 99%

“…In their analysis, no overall association between CXCL1, CXCR1 or CXCR2 expression and prognostic endpoints was found, although survival analysis demonstrated an inverse association between CXCL1 and recurrence-free survival in stage Ⅲ patients. Interestingly, CXCL8 positivity in the tumor infiltrate correlated with earlier disease stage and improved relapse-free survival in multivariate Cox regression analysis [180] . Schroepf et al [181] screened samples collected from 501 German patients with IBD (336 CD, 165 UC) including 258 children and 243 adults as well as 231 controls.…”

Section: Small and Large Intestinementioning

confidence: 99%

“…Synergistic upregulation with CXCL8 by diverse stimuli, induction by ERK2 and PI-3K/AKT pathway via PAR2 [175,178] CCL20, CXCL1/2, CXCL8 Remains high even after the treatment with anti-TNF antibody [179] CXCL1, CXCR1/2 Upregulation in stage II and III CRC, upregulation in stage Ⅱ and Ⅲ CRC [180] CXCR3 pathway CXCL9-pediatric Crohn's disease, CXCL11-UC in all age groups [181] Other chemokines IL-17 affects CXCL8, CXCL1, CCL20, CXCL10, CXCL11 and CCR5 in colon cancer cells [182] CXCL …”

Section: Cxcl10 Cxcl41mentioning

confidence: 99%

“…Upregulation along with the development of Crohn's disease, affecting biological responses of human intestinal microvascular endothelial cells in colitis model, positvely correlated with earlier disease stage and improved relapse-free survival [164,175,180] …”

Section: Cxcl8mentioning

confidence: 99%

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Chemokines, chemokine receptors and the gastrointestinal system

Miyazaki¹,

Takabe²,

Yeudall³

2013

WJG

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Core tip: The chemokine network makes an attractive target for therapeutic intervention in many tumor types, including those of the gastrointestinal tract. However, we need to define more selective and specific targets, to minimize systemic side effects during treatment. INTRODUCTION Cancer development and progression in the gastrointestinal tractCancer is a disease in which normal cells acquire genetic and epigenetic abnormalities [1,2] , leading to disorientation of conventional processes for the maintenance of normal cell physiology. These aberrant genetic and epigenetic modifications to the normal cell induce abnormal cell motility, proliferation, and survival, eventually enabling these cells to invade into adjacent tissues and even to migrate to regional or distant organs where they may grow continuously as metastatic lesions [3] . For many cancer patients, metastasis is generally the major cause of disease-related death [4,5] . Therefore, it is indispensable to elucidate the basic molecular mechanisms of tumor development to identify effective therapeutic targets, which can possibly reduce the side-effects of treatment, and define useful molecular markers for early detection and prediction of disease course. Especially, the newly emerged concept of personalized medicine may require in-depth assessment of potential therapeutic molecular target(s) in each individual case through analysis of sig- REVIEW Chemokines, chemokine receptors and the gastrointestinal system AbstractThe biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors, which include epidermal growth factor receptor agonists and members of the transforming growth factor β family. Furthermore, the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small, immunomodulatory proteins also play key roles in carcinogenesis and may, therefore, be potential targets for novel therapeutic approaches. In this review, we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.

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Section: Small and Large Intestinementioning

confidence: 99%

Section: Small and Large Intestinementioning

confidence: 99%

Section: Cxcl10 Cxcl41mentioning

confidence: 99%

Section: Cxcl8mentioning

confidence: 99%

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Chemokines, chemokine receptors and the gastrointestinal system

Miyazaki¹,

Takabe²,

Yeudall³

2013

WJG

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“…More than half a million people in the world annually are victims of it (Oladipo et al, 2011;Peddareddigari et al, 2010). This is also the third most common cancer among Asian men and women and its prevalence is increasing (Pourhoseingholi, 2012).…”

Section: Introductionmentioning

confidence: 99%

Evaluating the Expression of CD34 Marker in Colorectal Adenocarcinoma and its Relationship with Clinicopathologic Factors

Behbehani¹,

Ranjbari²,

Rahim³

et al. 2015

Asian J. of Cell Biology

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Colorectal cancer is known as one of the most common types of cancer which the prevalence is increasing. According to reports, malignancies of the large intestine have highly broken out in Iran. Several studies have shown the correlation between the CD34 cell surface markers and some cancers. In the present study, the relationship between the protein expression and clinico-pathologic characteristics was evaluated. In this study, 40 paraffin blocks belonged to patients with colorectal cancer referring to Imam Khomeini Hospital in Ahvaz during [2003][2004][2005][2006][2007][2008][2009][2010][2011][2012][2013] were studied by immunohistochemistry method. From 40 samples, 22 were males and 18 females. Their mean age was 56±17.9 years and ranging from 22-87 years. The mean tumor size was 5.1 cm ranging 11-1.5 cm. The most common site of involvement was in the right colon (45%) and the rarest site in the transverse colon (10%) and 75% was in poorly-differentiated state in terms of tumor grade. Generally, marker expression was positive in 13 cases and negative in 27 cases. The CD34 expression was significantly correlated with tumor size, tumor depth, degree of differentiation as well as lymphatic, vascular and neural invasions. A positive correlation was observed between the marker expression and pathological characteristics. Therefore, CD34 marker expression can be effective as a marker in the diagnosis of pathological characteristics of colorectal cancer. However, further studies with a large population are recommended.

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High CerS5 expression levels associate with reduced patient survival and transition from apoptotic to autophagy signalling pathways in colorectal cancer

Fitzgerald

Sheehan

Espina

et al. 2014

The Journal of Pathology CR

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Ceramide synthase 5 is involved in the de novo synthesis of ceramide, a sphingolipid involved in cell death and proliferation. In this study, we investigated the role of ceramide synthase 5 in colorectal cancer by examining ceramide synthase 5 expression, clinico‐pathological parameters and association with survival/death signalling pathways in cancer. Immunohistochemical analysis of CerS5 was performed on 102 colorectal cancer samples using tissue microarrays constructed from formalin‐fixed and paraffin‐embedded tissues. We found strong membranous ceramide synthase 5 staining in 57 of 102 (56%) colorectal cancers. A multivariate Cox regression analysis of ceramide synthase 5 expression adjusted for disease stage, differentiation and lymphovascular invasion revealed reduced 5‐year overall survival (p = 0.001) and 5‐year recurrence‐free survival (p = 0.002), with hazard ratios of 4.712 and 4.322, respectively. The effect of ceramide synthase 5 expression on tumourigenic processes was further characterised by reverse phase protein array analysis. Reverse phase protein arrays were generated from laser capture microdissection‐enriched carcinoma cells from 19 fresh‐frozen colorectal cancer tissues. Measurements of phosphorylation and total levels of signalling proteins involved in apoptosis, autophagy and other cancer‐related pathways revealed two distinct signalling networks; weak membranous ceramide synthase 5 intensity was associated with a proteomic network dominated by signalling proteins linked to apoptosis, whereas strong ceramide synthase 5 intensity was associated with a proteomic sub‐network mostly composed of proteins linked to autophagy. In conclusion, high ceramide synthase 5 expression was found in colorectal cancer tissue and was associated with poorer patient outcomes. Our findings suggest that this may be mediated by a transition from apoptotic to autophagy signalling pathways in ceramide synthase 5 High expressing tumours, thus implicating ceramide synthase 5 in the progression of colorectal cancer.

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The expression and prognostic impact of CXC-chemokines in stage II and III colorectal cancer epithelial and stromal tissue

Cited by 71 publications

References 43 publications

Chemokines, chemokine receptors and the gastrointestinal system

Chemokines, chemokine receptors and the gastrointestinal system

Evaluating the Expression of CD34 Marker in Colorectal Adenocarcinoma and its Relationship with Clinicopathologic Factors

High CerS5 expression levels associate with reduced patient survival and transition from apoptotic to autophagy signalling pathways in colorectal cancer

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