scholarly journals POS0417 EXOGENOUS CXCL5 RESTORES ENDOGENOUS BLOOD-TISSUE CHEMOKINE GRADIENT TO IMPROVE SURVIVAL IN MURINE LUPUS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 437.2-438
Author(s):  
F. Lim ◽  
D. Guo ◽  
J. Chen ◽  
A. Law ◽  
Z. Y. Poon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Serum Levels ◽  
Disease Stage ◽  
Molecular Pathways ◽  
Beta Catenin ◽  
Angiogenic Growth Factors ◽  
Immune Profile ◽  
Complement 3 ◽  
Luminex Technology ◽  
Chemokine Gradient

Background:Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease that is potentially fatal. There is an unmet need to improve current therapies. In patients with SLE, we observed that serum CXCL5 levels were significantly lower than healthy control subjects and negatively correlated with disease activity(1-9).Objectives:The aim of this study is to elucidate the effect of supplemental serum CXCL5 in abrogating the pathological processes of SLE.Methods:Ten doses of exogenous CXCL5 (3µg/kg) was administered to 16-week-old Faslpr mice weekly by intravenous injection. Mice were monitored for 10 weeks. Splenic immune profile was measured by flow cytometry. Circulating cytokine and immunoglobulin profile were detected by Luminex technology. Renal function was evaluated by urinary spot albumin creatinine ratio. In situ renal immune cell infiltration and complement 3 deposition were detected by Haematoxylin and Eosin (H&E) and immunohistochemistry staining. The molecular pathways involved were examined by RNA sequencing.Results:In Faslpr mice, intravenous administration of exogenous CXCL5 significantly improved mouse survival with concomitant reduction of autoantibody secretion, proteinuria, complement 3 deposition, neutrophil infiltration and lupus nephritis classes. Through evaluating the changes of immune profile, cytokine profile and molecular pathways, we found that intravenous CXCL5 reduced inflammation via an orchestral effect of regulating neutrophil trafficking and modulating helper T cell-mediated immune response. Pharmacokinetic and real-time Polymerase Chain Reaction studies further demonstrated that this orchestration was triggered by a cascade reaction - restoring vascular under-expressed CXCL5 by an exogenous stimulation, re-establishing the normal serum levels of endogenous CXCL5 and reverting the CXCL5 chemokine gradient between inflamed tissues and blood circulation.Conclusion:Managing the dysregulation of CXCL5 by exogenous supplement may provide a new option for SLE therapy.References:[1]Dufies M, Grytsai O, Ronco C, et al. New CXCR1/CXCR2 inhibitors represent an effective treatment for kidney or head and neck cancers sensitive or refractory to reference treatments. Theranostics. 2019;9(18):5332-5346. doi:10.7150/thno.34681[2]Yildirim K, Colak E, Aktimur R, et al. Clinical Value of CXCL5 for Determining of Colorectal Cancer. Asian Pac J Cancer Prev. Sep 26 2018;19(9):2481-2484. doi:10.22034/apjcp.2018.19.9.2481[3]Wu K, Yu S, Liu Q, Bai X, Zheng X. The clinical significance of CXCL5 in non-small cell lung cancer. Onco Targets Ther. 2017;10:5561-5573. doi:10.2147/ott.s148772[4]Zhao J, Ou B, Han D, et al. Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3beta/beta-catenin pathways. Mol Cancer. Mar 29 2017;16(1):70. doi:10.1186/s12943-017-0629-4[5]Han KQ, Han H, He XQ, et al. Chemokine CXCL1 may serve as a potential molecular target for hepatocellular carcinoma. Cancer Med. Oct 2016;5(10):2861-2871. doi:10.1002/cam4.843[6]Pappa CA, Tsirakis G, Kanellou P, et al. Monitoring serum levels ELR+ CXC chemokines and the relationship between microvessel density and angiogenic growth factors in multiple myeloma. Cytokine. Dec 2011;56(3):616-20. doi:10.1016/j.cyto.2011.08.034[7]Zhang L, Li H, Ge C, et al. CXCL3 contributes to CD133(+) CSCs maintenance and forms a positive feedback regulation loop with CD133 in HCC via Erk1/2 phosphorylation. Sci Rep. Jun 3 2016;6:27426. doi:10.1038/srep27426[8]Matsubara J, Honda K, Ono M, et al. Reduced plasma level of CXC chemokine ligand 7 in patients with pancreatic cancer. Cancer Epidemiol Biomarkers Prev. Jan 2011;20(1):160-71. doi:10.1158/1055- 9965.epi-10-0397[9]Ma Y, Ren Y, Dai ZJ, Wu CJ, Ji YH, Xu J. IL-6, IL-8 and TNF-alpha levels correlate with disease stage in breast cancer patients. Adv Clin Exp Med. May-Jun 2017;26(3):421-426. doi:10.17219/acem/62120Disclosure of Interests:None declared

scholarly journals Evaluation of serum levels of malondialdehyde and endogenous non-enzymatic antioxidants in relation to colorectal cancer stage and intestinal wall infiltration

2021 ◽  
Author(s):  
Ismar Rašić ◽  
Sandin Holjan ◽  
Vedad Papović ◽  
Sanjin Glavaš ◽  
Adi Mulabdić ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Uric Acid ◽  
Surgical Treatment ◽  
Serum Albumin ◽  
Tumor Invasion ◽  
Serum Levels ◽  
Intestinal Wall ◽  
Disease Stage ◽  
Control Group ◽  
Enzymatic Antioxidants

Introduction: Oxidative stress and lipid peroxidation are pointed as possible factors in the development of colorectal cancer (CRC). The aim of this study was to assess the serum malondialdehyde (MDA) and non-enzymatic antioxidants concentration (albumin, bilirubin, uric acid, and ferritin) and their relation with the stage and histopathologic size (pT) of CRC. Methods: One hundred and twenty patients with clinically and histopathologically confirmed CRC and the need for surgical treatment were included in a cross-sectional study. All patients were divided into groups according to the disease stage and depth of tumor invasion. The control group included 30 subjects with no signs of malignant and inflammatory bowel disease. The patients and controls did not receive vitamin supplementation. Peripheral venous blood was sampled before the surgical treatment of CRC patients and on the day of the examination of control subjects for determination of serum MDA and the concentration of the non-enzymatic antioxidants. Results: The serum levels of MDA were progressively increased in CRC patients with the highest level in the fourth stage of disease and pT4 group. Ferritin levels increased significantly with the CRC stage and decreased with the depth of bowel wall invasion. Serum albumin concentration significantly decreased with increasing stage and increasing depth of tumor invasion of the intestinal wall, while serum bilirubin level showed no change compared to the control group. Serum uric acid concentration was significantly higher in CRC patients, but no difference was observed with CRC progression. It was confirmed that serum albumin significantly negatively correlated with the CRC stage (rho = −0.649, p < 0.001), while serum MDA significantly positively correlated with the CRC stage (rho = 0.750, p < 0.001). Conclusion: These results indicate that serum MDA concentrations are related to the progression of CRC, to which the imbalance in non-enzymatic antioxidants also contributes.

scholarly journals Interhospital referral of colorectal cancer patients: a Dutch population-based study

2021 ◽  
Author(s):  
A. K. Warps ◽  
◽  
M. P. M. de Neree tot Babberich ◽  
E. Dekker ◽  
M. W. J. M. Wouters ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Waiting Time ◽  
Secondary Care ◽  
Advanced Disease ◽  
Waiting Times ◽  
Tertiary Care ◽  
Disease Stage ◽  
Colorectal Cancer Patients ◽  
Tertiary Care Hospitals

Abstract Purpose Interhospital referral is a consequence of centralization of complex oncological care but might negatively impact waiting time, a quality indicator in the Netherlands. This study aims to evaluate characteristics and waiting times of patients with primary colorectal cancer who are referred between hospitals. Methods Data were extracted from the Dutch ColoRectal Audit (2015-2019). Waiting time between first tumor-positive biopsy until first treatment was compared between subgroups stratified for referral status, disease stage, and type of hospital. Results In total, 46,561 patients were included. Patients treated for colon or rectal cancer in secondary care hospitals were referred in 12.2% and 14.7%, respectively. In tertiary care hospitals, corresponding referral rates were 43.8% and 66.4%. Referred patients in tertiary care hospitals were younger, but had a more advanced disease stage, and underwent more often multivisceral resection and simultaneous metastasectomy than non-referred patients in secondary care hospitals (p<0.001). Referred patients were more often treated within national quality standards for waiting time compared to non-referred patients (p<0.001). For referred patients, longer waiting times prior to MDT were observed compared to non-referred patients within each hospital type, although most time was spent post-MDT. Conclusion A large proportion of colorectal cancer patients that are treated in tertiary care hospitals are referred from another hospital but mostly treated within standards for waiting time. These patients are younger but often have a more advanced disease. This suggests that these patients are willing to travel more but also reflects successful centralization of complex oncological patients in the Netherlands.

scholarly journals Clinical significance of circulating tumor cell related markers in patients with epithelial ovarian cancer before and after adjuvant chemotherapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meysam Yousefi ◽  
Sara Rajaie ◽  
Vahideh Keyvani ◽  
Somayeh Bolandi ◽  
Malihe Hasanzadeh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Clinical Significance ◽  
Therapy Response ◽  
Serum Levels ◽  
Circulating Tumor Cell ◽  
Tumor Stage ◽  
Disease Stage ◽  
Before And After

AbstractCirculating tumor cells (CTCs) have recently been considered as new prognostic and diagnostic markers for various human cancers; however, their significance in epithelial ovarian cancer (EOC) remains to be elucidated. In this study, using quantitative real-time PCR, we evaluated the expression of EPCAM, MUC1, CEA, HE4 and CA125 mRNAs, as putative markers of CTCs, in the blood of 51 EOC patients before and/or after adjuvant chemotherapy. Our results demonstrated that, before chemotherapy, the expression of EPCAM, MUC1, CEA and HE4 mRNAs were correlated to each other. CEA expression was correlated with tumor stage (r = 0.594, p = 0.000) before chemotherapy, whereas its expression after chemotherapy was correlated with serum levels of CA125 antigen (r = 0.658, p = 0.000). HE4 mRNA showed the highest sensitivity both before and after chemotherapy (82.98% and 85.19%, respectively) and the persistence of this marker after chemotherapy was associated with advanced disease stage. The expression of CA125 mRNA had negative correlation with the other markers and with tumor stage and therapy response (evaluated by the measurement of serum CA125 antigen). Collectively, our results indicated a better clinical significance of tumor-specific markers (CEA and HE4 mRNAs) compared to epithelial-specific markers (EPCAM and MUC1 mRNAs).

scholarly journals 427 The Effect of Malnutrition on Early Outcomes after Cancer Surgery: An International Prospective Cohort Study in 82 Countries

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
A Riad ◽  
S Knight ◽  
E Harrison
Keyword(s):  
Colorectal Cancer ◽  
Cohort Study ◽  
Elective Surgery ◽  
Final Analysis ◽  
Cancer Surgery ◽  
Postoperative Outcomes ◽  
Disease Stage ◽  
Severe Malnutrition ◽  
Colorectal Cancer Surgery ◽  
After Cancer

Abstract Background Malnutrition is a state linked to worse postoperative outcomes, and cancer patients are particularly vulnerable due to cachexia. We aimed to explore the effect of malnutrition on 30-day mortality following gastric and colorectal cancer surgery. Method GlobalSurg3 was multicentre international cohort study which collected data from consecutive patients undergoing emergency or elective surgery for gastric and colorectal cancer. Malnutrition was defined using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Multilevel variable regression approaches determined the relationship between malnutrition and early postoperative outcomes. Results 6438 patients were included in the final analysis (1184 gastric cancer; 5254 colorectal cancer). Severe malnutrition was common across all income-strata, affecting 1 in 4 patients overall, with a higher burden in low and lower-middle income countries (64%). In patients undergoing elective surgery (n = 5709), severe malnutrition was independently associated with increased mortality (aOR = 1.62 (1.07-2.48, P = 0.024) after accounting for patient factors, disease stage and country effects. Conclusions Severe malnutrition represents a high global burden in cancer surgery, particularly within lower income settings. Malnutrition is an independent risk-factor for 30-day mortality following elective surgery for gastric and colorectal cancer, suggesting perioperative nutritional interventions may improve outcomes after cancer surgery.

Serum Concentration of Reg IV in Patients with Colorectal Cancer: Overexpression and High Serum Levels of Reg IV Are Associated with Liver Metastasis

Oncology ◽  
2007 ◽  
Vol 72 (5-6) ◽  
pp. 371-380 ◽  
Author(s):  
Naohide Oue ◽  
Hiroki Kuniyasu ◽  
Tsuyoshi Noguchi ◽  
Kazuhiro Sentani ◽  
Masanori Ito ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Serum Concentration ◽  
Serum Levels ◽  
High Serum

scholarly journals Deciphering the molecular pathways disrupted in normal and neoplastic colonic tissue in inherited colorectal cancer syndromes

2011 ◽  
Vol 9 (Suppl 1) ◽  
pp. O6
Author(s):  
Deborah W Neklason ◽  
Michelle W Done ◽  
Brett Milash ◽  
Lewis Frey ◽  
Nykole Sargent ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Pathways ◽  
Colonic Tissue ◽  
Cancer Syndromes

scholarly journals Radix Tetrastigma hemsleyani flavone exhibits antitumor activity in colorectal cancer via Wnt/β-catenin signaling pathway

2018 ◽  
Vol Volume 11 ◽  
pp. 6437-6446 ◽  
Author(s):  
Xiaowei Wu ◽  
Na Yu ◽  
Yuping Zhang ◽  
Yuanning Ye ◽  
Wenrong Sun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Antitumor Activity ◽  
Signaling Pathway ◽  
Beta Catenin

scholarly journals Serum Levels of BDNF in Patients with Adenoma and Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Zhe Wang ◽  
Shuang Wang ◽  
Yu Liu ◽  
Shan Gao ◽  
Yunqing Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Diagnostic Performance ◽  
Serum Levels ◽  
Tnm Staging ◽  
Laboratory Method ◽  
Healthy Controls ◽  
Tumor Differentiation ◽  
Combined Detection ◽  
Control Study ◽  
Serum Bdnf

The present study is aimed at examining the serum levels of brain-derived neurotrophic factor (BDNF) and investigating its role in differential diagnosis of colorectal cancer (CRC). Materials and Methods. In a Chinese population, we conducted a case-control study to compare the diagnostic performance of serum levels of BDNF and carcinoembryonic antigen (CEA) for CRC. We enrolled 61 healthy controls, 31 patients with adenomas, and 81 patients with CRC. We explored the correlation between serum levels of BDNF and several pathological features, such as tumor differentiation and TNM staging. Results. The serum levels of BDNF were significantly ( p < 0.0001 ) higher in patients with CRC ( 10.64 ± 3.84 , n = 81 ) than in the healthy controls ( 4.69 ± 1.69   ng / mL , n = 61 ). Serum BDNF also correlated with tumor size, tumor differentiation, and TNM staging ( p < 0.05 ). For early diagnosis, the combination of BDNF (AUC 0.719; 95% CI, 0.621–0.816) and CEA (AUC 0.733; 95% CI, 0.632–0.909) slightly improved the diagnostic performance for CRC (AUC 0.823; 95% CI, 0.737-0.909). Conclusions. Combined detection of serum BDNF and CEA may thus have the potential to become a new laboratory method for the early clinical diagnosis of CRC.

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