Potential Role of Soluble CD40 Ligand as Inflammatory Biomarker in Colorectal Cancer Patients

2014 ◽  
Vol 29 (3) ◽  
pp. 261-267 ◽  
Author(s):  
Violetta Dymicka-Piekarska ◽  
Aleksandra Korniluk ◽  
Mariusz Gryko ◽  
Elzbieta Siergiejko ◽  
Halina Kemona
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
High Efficiency ◽  
Inflammatory Marker ◽  
Area Under The Curve ◽  
Distant Metastases ◽  
Cd40 Ligand ◽  
Soluble Cd40 Ligand ◽  
Inflammatory Biomarker

Platelet activation observed in cancer patients is associated with the release of various cytokines, including P-selectin and CD40 ligand (CD40L). We analyzed the plasma levels of sCD40L in association with adhesion molecules (sP-selectin and sVCAM-1) to check the hypothesis of a possible involvement in cancer progression. Blood samples were obtained from 59 patients with different stages of colorectal cancer (CRC) and 29 age and gender-matched control subjects. Plasma sCD40L, sP-selectin, and sVCAM-1 concentrations were measured with quantitative sandwich enzyme-linked immunoassay. All patients with CRC had significantly higher levels of sCD40L (p<0.001), sP-selectin (p<0.02), and sVCAM-1 (p<0.03), as compared to healthy subjects. The level of sCD40L significantly correlated with sP-selectin (p<0.05) in patients with distant metastases to the liver. We also observed a high negative correlation between sP-selectin and platelets count (p<0.02) in patients with lymph node metastasis. The receiver-operator curve for CRC patients indicated that the area under the curve for sCD40L was 0.915, which may indicate its high efficiency as an inflammatory marker. In our study, the sCD40L correlated with sP-selectin in patients with advanced stage of CRC, which might indicate its possible participation in metastasis formation.

472 Addressing the Quality of Hospital Care of Colorectal Cancer Patients Undergoing Surgery: What Did We Learn from the National Bowel Cancer Audit?

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
C Li ◽  
S Z Y Ooi ◽  
T Woo ◽  
P H M Chan
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
External Validation ◽  
Distant Metastases ◽  
Management Plan ◽  
Bowel Cancer ◽  
Clinical Factors ◽  
Quality Outcomes ◽  
Colorectal Cancer Patients

Abstract Aim To identify the most relevant clinical factors in the National Bowel Cancer Audit (NBOCA) that contribute to the variation in the quality of care provided in different hospitals for colorectal cancer patients undergoing surgery. Method Data from 36,116 patients with colorectal cancer who had undergone surgery were retrospectively collected from the NBOCA and analysed from 145 and 146 hospitals over two years. A validated multiple linear regression was performed to compare the identified clinical factors with various quality outcomes. The quality outcomes defined in this study were the length of hospitalisation, 2-year mortality, readmission rate, 90-day mortality, and 18-month stoma rate. Results Four clinical factors (laparoscopy rate, abdominal-perineal-resection-of-rectum (APER), pre-operative radiotherapy and patients with distant metastases) were shown to have a significant (p &lt; 0.05) impact on the length of hospitalisation and 18-month stoma rate. 18-month stoma rate was also significantly associated with 2-year mortality. External validation of the regression model demonstrated the Root-Mean-Square-Error of 0.811 and 4.62 for 18-month stoma rate and 2-year mortality respectively. Conclusions Hospitals should monitor the four clinical factors for patients with colorectal cancer during perioperative care. Clinicians should consider these factors along with the individual patients’ history when formulating a management plan for patients with colorectal cancer.

scholarly journals Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jiao Wu ◽  
Sai-Ching Jim Yeung ◽  
Sicheng Liu ◽  
Aiham Qdaisat ◽  
Dewei Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Weight Loss ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Colorectal Cancer Patient ◽  
Nutrition Support ◽  
Immunodeficient Mice ◽  
The Impact

AbstractWeight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

scholarly journals CXCL-8 in Preoperative Colorectal Cancer Patients: Significance for Diagnosis and Cancer Progression

2020 ◽  
Vol 21 (6) ◽  
pp. 2040 ◽  
Author(s):  
Sara Pączek ◽  
Marta Łukaszewicz-Zając ◽  
Mariusz Gryko ◽  
Piotr Mroczko ◽  
Agnieszka Kulczyńska-Przybik ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Marker ◽  
Cancer Progression ◽  
Characteristic Curve ◽  
Distant Metastases ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Predictive Values ◽  
Potential Biomarker ◽  
Tumor Stages

Introduction. Since colorectal cancer (CRC) is the second most commonly diagnosed malignancy in Europe and third worldwide, novel biomarkers for diagnosing the disease are critically needed. Objectives. According to our knowledge, the present study is the first to evaluate the clinical usefulness of serum CXCL-8 (C-X-C motif chemokine 8) in the diagnosis and progression of CRC compared to classical tumor marker CEA (carcinoembryonic antigen) and marker of inflammation CRP (C-reactive protein). Patients and Methods. The study included 59 CRC patients and 46 healthy volunteers. Serum levels of selected proteins were measured using ELISA (enzyme-linked immunosorbent assay), CMIA (chemiluminescent microparticle immunoassay), and immunoturbidimetric methods. Results. Serum concentrations of CXCL-8, similarly to those of the classical tumor marker CEA and inflammatory state marker CRP, were significantly higher in CRC patients than in healthy controls. There were statistically significant differences in CXCL-8 concentrations between tumor stages, as established by the Kruskal–Wallis test and confirmed by the post hoc Dwass–Steele–Critchlow–Fligner test. CXCL-8 levels were also significantly elevated in CRC patients with distant metastases compared to patients in the subgroup without metastases. Diagnostic sensitivity, predictive values for negative results (NPV), and AUC (area under the Receiver Operating Characteristic Curve—ROC curve) of CXCL-8 were higher than those of CEA, while diagnostic specificity and predictive values for positive results (PPV) of CXCL-8 were higher than those of CRP. Conclusions. Our findings indicate greater utility of CXCL-8 in comparison to the classical tumor marker CEA in the diagnosis of CRC. Moreover, serum CXCL-8 might be a potential biomarker of colorectal cancer progression.

scholarly journals Establishment of prognostic nomogram for elderly colorectal cancer patients: a SEER database analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Chaoran Yu ◽  
Yujie Zhang
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Area Under The Curve ◽  
Seer Database ◽  
Tumor Node Metastasis ◽  
Database Analysis ◽  
Cancer Specific Survival ◽  
Decision Curve Analysis ◽  
Node Metastasis ◽  
Colorectal Cancer Patients

Abstract Background This study aimed to establish nomogram models of overall survival (OS) and cancer-specific survival (CSS) in elderly colorectal cancer (ECRC) patients (Age ≥ 70). Methods The clinical variables of patients confirmed as ECRC between 2004 and 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analysis were performed, followed by the construction of nomograms in OS and CSS. Results A total of 44,761 cases were finally included in this study. Both C-index and calibration plots indicated noticeable performance of newly established nomograms. Moreover, nomograms also showed higher outcomes of decision curve analysis (DCA) and the area under the curve (AUC) compared to American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) stage and SEER stage. Conclusions This study established nomograms of elderly colorectal cancer patients with distinct clinical values compared to AJCC TNM and SEER stages regarding both OS and CSS.

5-fluorouracil (5FU) pharmacokinetic and hormonal status in female colorectal cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13576-13576
Author(s):  
A. Bononi ◽  
M. Gusella ◽  
G. Crepaldi ◽  
R. Padrini ◽  
E. Ferrazzi
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Plasma Levels ◽  
Elderly Women ◽  
Performance Status ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Hormonal Status ◽  
Significant Difference ◽  
Colorectal Cancer Patients

13576 Background: It is well known that females present a significantly reduced clearance of 5FU compared to males treated with the same doses.We tested the hypothesis that it may depend on the hormonal status, so that pre-menopausal women would have different 5FU pharmacokinetics compared with both postmenopausal women and elderly women. Methods: 48 colorectal cancer patients were prospectively studied: all of them were on adjuvant treatment based on 5FU repeated boluses. On the second day of the first cycle peripheral blood was drawn after drug administration. Plasma level were detected by HPLC analysis and pharmacokinetic parameters were calculated trough a one phase exponential decay model. Results: All patients had 100–90 Karnosky Performance status score. 12 were in pre-menopausal phase (age range : 40–55 years); among the others we distinguished a younger 19 people group (age lower than 70 years old) and an elderly 17 patient group (age equal or higher than 70 years old). They received a 5FU mean dose of 406 ± 15 mg/mq, not significantly different among the three groups. After intravenous bolus injection a high interindividual variability of 5-FU pharmacokinetics was detected: AUC0-∞ (area under the curve of drug plasma levels versus time) ranged between 368 and 1236 mg × min/L and the highest values (>1000) were found in two elderly patients, considered fit; anyway there was no significant difference among AUC of the three groups. 5FU total clearance ranged between 0.53 and 1.9 L/min and means were 1.07 ± 0.3, 1.02 ± 0.3 and 0.98 ± 0.3 L/min in pre-menopausal, postmenopausal and elderly women respectively; again 5FU clearance/ BSA (body surface area), half live elimination times and peak concentration plasma levels were not significantly different among the three groups. Conclusions: It seems that sexual hormonal status do not influence 5FU total body elimination capability, and that pharmacokinetic differences between genders should be related to other factors,as for example Body Composition. Funded by AIRC-Veneto No significant financial relationships to disclose.

Upregulation lnc-NEAT1 contributes to colorectal cancer progression through sponging miR-486-5p and activating NR4A1/Wnt/β-catenin pathway

2020 ◽  
pp. 1-11
Author(s):  
Zhining Liu ◽  
Yimei Gu ◽  
Xiaohu Cheng ◽  
Heng Jiang ◽  
Yang Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Colorectal Cancer Cells ◽  
Colorectal Cancer Progression ◽  
Colorectal Cancer Patients ◽  
Cancer Tissues

Colorectal cancer is a major public health problem and fourth guiding cause of cancer-induced mortality worldwide. The five-year survival rate for patients with colorectal cancer remains poor, and almost half of colorectal cancer patients present recurrence and die within five years. The increasing studies showed that long non-coding RNA (lncRNA) was involved in colorectal cancer. Therefore, this study was used to explore molecular mechanisms of nuclear paraspeckle assembly transcript 1 (NEAT1) in colorectal cancer. The real-time quantitative polymerase chain reaction (RT-qPCR) was employed to estimate the expression levels of NEAT1, Nuclear receptor 4 A1 (NR4A1), and miR-486-5p in colorectal cancer tissues and cells. Kaplan-Meier curve was conducted to analyze relationship between survival time of colorectal cancer patients and level of NEAT1. The protein levels of NR4A1, β-catenin, c-Myc, and cyclinD1 were assessed with western blot assay. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and flow cytometry assays were performed to evaluate proliferation and apoptosis of colorectal cancer cells, respectively. The migration and invasion abilities of cells were examined by transwell assay. The relationship between miR-486-5p and NEAT1 or NR4A1 was confirmed by dual-luciferase reporter assay. We found NEAT1 and NR4A1 were highly expressed in colorectal cancer tissues and cell lines compared with controls. Loss-functional experiments revealed that knockdown of NEAT1 or NR4A1 repressed proliferation and motility, while inducing apoptosis of colorectal cancer cells. The gain of NR4A1 could abolish NEAT1 silencing-induced effects in colorectal cancer cells. In addition, NEAT1 contributed to colorectal cancer progression through mediating NR4A1/Wnt/β-catenin signaling pathway. In conclusion, NEAT1 stimulated colorectal cancer progression via acting as competing endogenous RNA to sponge miR-486-5p and regulate NR4A1/Wnt/β-catenin signaling pathway.

Evaluating variability in fluorouracil (FU) exposure in obese and non-obese patients with colorectal cancer using full weight-based dosing.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 409-409
Author(s):  
Jai Narendra Patel ◽  
Allison Mary Deal ◽  
Howard L. McLeod ◽  
Bert H. O'Neil ◽  
Christine Marie Walko
Keyword(s):  
Colorectal Cancer ◽  
Body Weight ◽  
Cancer Patients ◽  
Drug Exposure ◽  
Pearson Correlation ◽  
Area Under The Curve ◽  
Primary Objective ◽  
Obese Patients ◽  
Optimal Drug ◽  
Significant Difference

409 Background: Approximately 30% of cancer patients are obese. Controversy exists on how to best use body weight to safely and effectively dose chemotherapy. Additionally, body surface area (BSA)-based dosing is associated with high pharmacokinetic (PK) variability and is a poor indicator of optimal drug exposure. Methods: We estimated FU exposure post cycle 1, as indicated by area under the curve (AUC), in 58 colorectal cancer patients receiving mFOLFOX6 (FU 2400 mg/m2 [BSA calculated using actual body weight (ABW)] over 46 hours) +/- bevacizumab. AUCs were determined using an immunoassay at Myriad Laboratories. The primary objective was to identify variability in FU exposure in obese and non-obese patients using body mass index (BMI), BSA, and ABW. Groups were compared using two group t-tests. Results: No significant difference in AUC was observed between obese (BMI ≥ 30 kg/m2) and non-obese (< 30 kg/m2) patients. A significantly lower AUC was observed in patients with a BSA ≥ 2.0 m2 compared to those < 2.0 m2 (p=0.02). The AUC for obese and non-obese patients ranged from 7-34 and 12-38 mg*hr/L, respectively. Only 32% and 28% of obese and non-obese patients, respectively, were within the previously reported therapeutic target AUC 20-25 mg*hr/L. Males had significantly lower AUCs compared to females (mean 18.7 v 22.4, p=0.03). FU AUC was not strongly correlated with BMI, BSA, or ABW (Pearson correlation of -0.03, -0.26, and -0.15, respectively). Conclusions: BSA-based dosing is associated with variable FU exposure. Lower AUCs in patients with a BSA ≥ 2.0 m2 supports both ASCO recommendations for full-weight-based dosing in obese patients and the value of dosing assessment across patient populations. Further study of AUC-based dosing is warranted as our data do not support a reduction in variable exposure based on BMI, BSA, or ABW dosing. [Table: see text]

Predictive Role of the UGT1A1, UGT1A7, and UGT1A9 Genetic Variants and Their Haplotypes on the Outcome of Metastatic Colorectal Cancer Patients Treated With Fluorouracil, Leucovorin, and Irinotecan

2009 ◽  
Vol 27 (15) ◽  
pp. 2457-2465 ◽  
Author(s):  
Erika Cecchin ◽  
Federico Innocenti ◽  
Mario D'Andrea ◽  
Giuseppe Corona ◽  
Elena De Mattia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Objective Response ◽  
Area Under The Curve ◽  
Reference Sequence ◽  
Hematologic Toxicity ◽  
Pharmacokinetic Data ◽  
Severe Toxicity ◽  
Colorectal Cancer Patients

Purpose UGT1A1★28 is considered the main pharmacogenetic predictor of the toxicity outcome of irinotecan-treated patients. We evaluated the effect of other UGT1A variants and haplotypes involved in 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronidation on severe toxicity and efficacy of fluorouracil, leucovorin, and irinotecan (FOLFIRI). Patients and Methods In addition to UGT1A1★28, UGT1A1★60, UGT1A1★93, UGT1A7★3, and UGT1A9★22 were genotyped in 250 metastatic colorectal cancer patients, and associations with severe hematologic and nonhematologic toxicity, objective response, time to progression (TTP), and overall survival were evaluated. In a subset of 71 patients, pharmacokinetic data were also available. Results UGT1A7★3 was the only marker of severe hematologic toxicity after the first cycle (odds ratio [OR], 3.94; 95% CI, 1.05 to 14.82; P = .04) in a multivariate analysis. It was also associated with glucuronidation ratio (SN-38G area under the curve [AUC]/SN-38 AUC) and biliary index (irinotecan AUC) × (SN-38 AUC/SN-38G AUC). Haplotype I (all the reference sequence alleles but UGT1A9★22) was a predictor of severe hematologic toxicity during the entire course of therapy (OR, 0.39; 95% CI, 0.19 to 0.82; P = .01), together with sex (OR, 2.08; 95% CI, 1.01 to 4.28; P = .05). In addition to UGT1A1★28, haplotype II (all the variant alleles but UGT1A9★22) was associated with a response rate (OR, 8.61; 95% CI, 1.75 to 42.38; P = .01). UGT1A1★28 was the only marker associated with TTP. Conclusion We propose that UGT1A variants additional to UGT1A1★28 might improve the prediction of the outcome of colorectal cancer patients treated with FOLFIRI. A UGT1A haplotype-based approach might be an efficacious strategy to achieve treatment individualization of FOLFIRI.

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