Anemia of inflammation in patients with colorectal cancer: Correlation with Interleukin-1, Interleukin-33 and Galectin-1

Journal of Medical Biochemistry ◽

10.5937/jomb0-30135 ◽

2021 ◽

Author(s):

Miodrag Jocic

Keyword(s):

Colorectal Cancer ◽

Interleukin 1 ◽

Roc Curves ◽

Microcytic Anemia ◽

Blood Vessel Invasion ◽

Range Analysis ◽

Mutual Correlation ◽

Interleukin 33 ◽

Colorectal Cancer Patients ◽

Anemia Of Inflammation

Purpose: Patients with colorectal cancer (CRC) have anemia often present as a consequence of chronic bleeding from tumor. The exact role of lL-33, Galectin-l and IL-l in the pathological genesis of anemia in colorectal cancer patients has not been elucidated yet. The main goal of this research was to analyze Gal-l, IL-l and lL-33 systemic values in anemic and non-anemic CRC patients. Methods: Concentrations of IL-33, Galectin-1 and IL-1 have been studied in blood samples of 55 CRC patients (27 without anemia and 28 with anemia). Results: CRC patients with anemia had more severe and local advanced disease compared to CRC non-anemic patients. Anemia positively correlated with higher nuclear grade, lymph and blood vessel invasion, as well as with higher TNM stage, detectable metastatic lesions in lung and liver and peritoneal carcinomatosis. Significantly higher IL-33, Gal-1 and IL-1 concentration have been found in sera of patients with CRC and detected anemia. CRC patients mostly had microcytic anemia, while ferritin values were in normal range. Analysis revealed positive mutual correlation between serum values of galectin-1, IL-1 and IL-33 in CRC patients. Level of hemoglobin negatively correlated with serum IL-33, Gal-1 and IL-1. We have analyzed the Receiver Operating Characteristic (ROC) curves of serum IL-33, Gal-1 and IL-1 showed that these cytokines can be treated as additional markers for anemia of inflammation in CRC patients. Conclusions: Predomination of Galectin-1, IL-1 and IL-33 in anemic CRC patients implicates on their potential role in anemia genesis and further development.

Download Full-text

MABp1 to improve clinical outcomes of patients with symptomatic refractory metastatic colorectal cancer patients: Per-protocol population analysis of phase III study (PT026).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3530 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3530-3530

Author(s):

Lucjan Wyrwicz ◽

Mark P. Saunders ◽

Thierry Andre ◽

Tomasz Sarosiek ◽

Radim Nemecek ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Primary Endpoint ◽

Population Analysis ◽

Interleukin 1 ◽

Phase Iii ◽

Protocol Population ◽

Toxic Agents ◽

Phase Iii Study ◽

Colorectal Cancer Patients

3530 Background: Refractory metastatic colorectal cancer (mCRC) patients derive minimal benefit from further exposure to toxic agents. MABp1 is an anti-interleukin 1 alpha antibody that is shown to prolong survival (NCT01767857) and improves outcomes when assessed with a primary endpoint based on a constellation of objective and patient self-reported measures (NCT02138422) (Hickish T. et al Lancet Oncology 2017). In the latter study, clinically advanced patients were enrolled (symptomatic, ECOG 1,2), and 18% of patients progressed prior to reaching the endpoint assessments. Here we present the outcomes in per-protocol population (PP), those patients completing week 8 assessments. Methods: 309 patients randomized 2:1 to receive MABp1 versus placebo. Patients were ECOG 1-2, with mCRC refractory to chemotherapy, any degree of weight loss, and cancer-associated symptoms. The composite primary endpoint assessed the rate of patients achieving stabilization or improvement in lean body mass (LBM) and two of three symptom measures (pain, fatigue, appetite loss) from screening to the week 8 assessment. The study was designed for placebo cross-over, thus OS analysis for MABp1 vs placebo was not possible. Results: 57 patients (38 MABp1 [18%] and 19 placebo [19%]) discontinued study prior to the week 8 assessment due to disease progression, including 17 (8%) and 11 (11%) deaths in MABp1 and placebo respectively. 62% of placebo patients received MABp1 after 8 weeks. 252 patients, 40% in MABp1 (68/169) vs 23% in placebo (19/83) met the primary endpoint (p = 0.003). 139 patients were available for PP survival analysis (90 MABp1 vs 49 Placebo). Median OS of those achieving the primary endpoint was 11.7 months vs 5.7 months for those that did not (HR 0.39; p < 0.0001). Radiographic stable disease was improved (42% vs 12%; p < 0.001) and incidence of SAEs (6% vs 15%; p = 0.11) reduced in those achieving the primary endpoint. Conclusions: Achieving the primary endpoint was associated with improvement in outcomes, RECIST stabilization, SAEs and survival. Further study should confirm the effect of MABp1 on survival in this population. Clinical trial information: NCT02138422.

Download Full-text

Profile of Circulating Levels of Interleukin-1 Receptor Antagonist and Interleukin-6 in Colorectal Cancer Patients

Scandinavian Journal of Gastroenterology ◽

10.1080/003655299750024959 ◽

1999 ◽

Vol 34 (11) ◽

pp. 1139-1143 ◽

Cited By ~ 35

Author(s):

H. Ito, C. Miki

Keyword(s):

Colorectal Cancer ◽

Receptor Antagonist ◽

Cancer Patients ◽

Interleukin 6 ◽

Interleukin 1 ◽

Interleukin 1 Receptor Antagonist ◽

Colorectal Cancer Patients ◽

Circulating Levels

Download Full-text

Interleukin-1 Receptor Antagonists and Other Markers in Colorectal Cancer Patients

Scandinavian Journal of Gastroenterology ◽

10.3109/00365529709025103 ◽

1997 ◽

Vol 32 (6) ◽

pp. 577-581 ◽

Cited By ~ 11

Author(s):

H. Iwagaki ◽

A. Hizuta ◽

N. Tanaka

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Interleukin 1 ◽

Receptor Antagonists ◽

Colorectal Cancer Patients

Download Full-text

Fecal galectin-1 as a potential marker for colorectal cancer and disease severity

Vojnosanitetski pregled ◽

10.2298/vsp171201007j ◽

2019 ◽

Vol 76 (10) ◽

pp. 1037-1044 ◽

Cited By ~ 1

Author(s):

Milan Jovanovic ◽

Nevena Gajovic ◽

Natasa Zdravkovic ◽

Marina Jovanovic ◽

Milena Jurisevic ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Tissue ◽

Liquid Fraction ◽

Interleukin 1 ◽

Blood Vessel Invasion ◽

Enzyme Linked Immunosorbent Assay ◽

Specific Marker ◽

Histological Differentiation ◽

Potential Marker ◽

Advanced Tumor

Background/Aim. Colorectal cancer (CRC) represents one of the most common cancers worldwide. CRC is frequently diagnosed at advanced stages with poor prognosis, indicating the need for new diagnostic and prognostic markers. The aim of this study was to determine systemic and fecal values of galectin- 1 (gal-1) and ratios between gal-1 and proinflammatory cytokines: tumor necrosis factor-alpha (TNF-?), interleukin-1 beta (IL-1?) and interferon gamma (IFN-?), in the patients with CRC and the relationship with clinicopathological aspects of the disease. Methods. The blood samples and feces liquid fraction of 58 patients with CRC were analyzed. The serum and fecal levels of TNF-?, IL-1? and IFN-? and gal-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Results. The fecal level of gal-1 was increased in the CRC patients with higher nuclear grade and poor tumor tissue differentiation. The gal-1/TNF-? ratio in the serum and feces had a higher trend in the patients with the advanced tumor-nodemetastasis (TNM) stage as well as the detectable lymphatic and blood vessel invasion. The gal-1/TNF-? and gal-1/IFN-? ratios were increased in the serum of patients with presence of lung/liver metastasis or peritoneal carcinomatosis, while the enhanced gal-1/IL-1 ratio was detected only in the serum of patients with lung metastasis. A positive correlation between the gal-1 value in feces and histological differentiation of tumor and biomarkers alpha-fetoprotein (AFP) and cancer antigen- 19-9 (CA 19-9), respectively, was also observed. The fecal values of gal-1 higher than 13,708.29 pg/g presented a highly sensitive and specific marker for histological differentiation of tumor tissue. Conclusion. We believe that the predomination of gal-1 over pro-inflammatory cytokines TNF-?, IL-1? and IFN- ? in the patients with advanced and progressive CRC may implicate on an immunomodulatory role of gal-1 in the limiting ongoing proinflammatory processes. The fecal values of gal-1 can be used as a valuable marker for the severity of CRC.

Download Full-text