Intra‐tumoral interleukin‐6 down‐regulation system and genetic mutations of tumor suppressor genes in colorectal carcinoma

Miki, Chikao; Tonouchi, Hitoshi; Wakuda, Reiko; Hatada, Tsuyoshi; Inoue, Yasuhiro; Minato, Eiji; Kobayashi, Minàko; Kusunoki, Masato

doi:10.1002/cncr.10324

Cited by 28 publications

(21 citation statements)

References 27 publications

(32 reference statements)

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“…In colorectal cancers, IL-6-IL-1ra network system is associated with the allelic loss of a portion of chromosome 18q, reflecting the genetic alteration of tumor suppressor genes. 21) This finding suggests that since an extensive rise of IL-6 levels in the tumor component leads to mutate the alleles in molecular components, tumor cells may continue to activate the growth of tumors in eternity.…”

Section: Discussionmentioning

confidence: 99%

Does Postoperative Serum Interleukin-6 Influence Early Recurrence after Curative Pulmonary Resection of Lung Cancer?

Kita

Shiraishi

Watanabe

et al. 2011

ATCS

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after the date of enrollment of the last patient, we investigated survival status of each patient and identified a group with recurrence. Results: Among 107 patients, 29 patients developed recurrence with a mean follow-up of 18.1 months (range 14 to 21). P-stage was significantly more advanced in the recurrence group than in the non-recurrence group (p = 0.005). Serum IL-6 levels on POD 1 were significantly higher in the recurrence group than in the non-recurrence group (p = 0.007). In Cox's proportional hazards regression, P-stage and serum IL-6 levels on POD 1 were significant independent predicting factors for postoperative early recurrence (p = 0.006, p = 0.003). Conclusions: The higher the serum IL-6 levels on POD 1, the higher the risk of early postoperative recurrence, even when curative pulmonary resection can be accomplished in lung cancer patients.

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Section: Discussionmentioning

confidence: 99%

Does Postoperative Serum Interleukin-6 Influence Early Recurrence after Curative Pulmonary Resection of Lung Cancer?

Kita

Shiraishi

Watanabe

et al. 2011

ATCS

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“…Malignant cells, including colorectal cancer tumor cells, have been found to produce IL-6. 22,[28][29][30] In colorectal carcinoma, IL-6 has been found localized in the tumor cytoplasm by immunohistochemical staining, indicating that these cells are capable of IL-6 production in situ. 22,30 The IL-6 concentration in tumor tissue was significantly higher than in normal mucosa and correlated with the serum IL-6 concentration.…”

Section: Discussionmentioning

confidence: 99%

“…22,[28][29][30] In colorectal carcinoma, IL-6 has been found localized in the tumor cytoplasm by immunohistochemical staining, indicating that these cells are capable of IL-6 production in situ. 22,30 The IL-6 concentration in tumor tissue was significantly higher than in normal mucosa and correlated with the serum IL-6 concentration. 22 In a study by Piancatelli et al 35 IL-6 mRNA was expressed in tumor tissue in 83% of patients with colorectal carcinoma.…”

Section: Discussionmentioning

confidence: 99%

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Preoperative interleukin‐6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma

Clinchy

Fransson

Druvefors

et al. 2007

Cancer

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BACKGROUND.Colorectal cancer is one of the most common forms of cancer in the Western world. Staging based on histopathology is currently the most accurate predictor of outcome after surgery. Colorectal cancer is curable if treated at an early stage (stage I‐III). However, for tumors in stages II and III there is a great need for tests giving more accurate prognostic information defining the patient population in need of closer follow‐up and/or adjuvant therapy. Furthermore, tests that provide prognostic information preoperatively could provide a guide both for preoperative oncologic treatment and the surgical procedure.METHODS.Peripheral blood mononuclear cells (PBMCs) were isolated preoperatively, within a week before primary surgery, from 39 patients undergoing surgery for colorectal cancer. The PBMCs were cultured in vitro for 24 hours in the presence of autologous serum and lipopolysaccharide (LPS). Interleukin‐6 (IL‐6) production was measured with enzyme‐linked immunosorbent assay (ELISA). Staging based on histopathology was performed in all patients. Patients were followed for at least 54 months.RESULTS.A production of >5000 pg/mL of IL‐6 identified colorectal cancer patients with a poor prognosis. Eight out of 13 patients with >5000 pg/mL IL‐6 died from cancer within the follow‐up period, whereas no cancer‐related deaths were recorded among 21 patients with 5000 pg/mL IL‐6 or less. A multivariate Cox regression analysis, stratified for T‐ and N‐stage, identified IL‐6 production as an independent prognostic factor.CONCLUSIONS.IL‐6 production in vitro by PBMC can predict survival after radical surgery for colorectal cancer. Cancer 2007. © 2007 American Cancer Society.

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“…These circumstances may imply a role for IL-17 in colorectal carcinogenesis. Elevation of proinflammatory cytokines, such as IL-1β and IL-6, is considered to be associated with colorectal cancer [59,60]. In an in vitro assay, IL-17 induced secretion of IL-1β from macrophages and has been shown to stimulate epithelial and fibroblastic cells to secrete IL-6 [52,61].…”

Section: Bmentioning

confidence: 99%

Interleukin-17 may be a valuable serum tumor marker in patients with colorectal carcinoma

Radosavljević

Ljujić²,

Jovanović³

et al. 2010

neo

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The promotion of tumor growth is due to a combination of several mechanisms, including angiogenesis and the abundance of cell-derived inflammatory cytokines. The aim of this study was to investigate the serum levels of interleukin 17 (IL-17) and the expression of p53 and Vascular Endothelial Growth Factor (VEGF), in order to determine the relationship between these markers and serum IL-17 levels in patients with colorectal carcinoma.Serum levels of the proinflammatory cytokine IL-17 in patients with colorectal carcinoma (CRC) (n=40) and in a healthy group (n=37) were analysed by ELISA. Surgically resected specimens of 59 colorectal carcinomas were studied by immunohistochemical staining for VEGF and p53.Analyses by ELISA showed significantly higher IL-17 serum levels in patients with colorectal carcinoma than in control subjects (IL-17; mean 128.52±47.62 pg/ml vs. mean 101.91±22.46 pg/ml; p=0.022). We also found an inverse correlation between p53 expression and the level of IL-17 in the serum of patients with CRC. In fact, the serum concentration of IL-17 was significantly higher in patients who did not express p53 (p=0.023). There was no significant correlation between the expression of p53 and VEGF. However, concomitant expression of VEGF and p53 showed a significant correlation with the histological and nuclear grade of the carcinoma.The data presented in our study indicate that IL-17 might act as a valuable tumor marker in patients with CRC and that combined analysis of p53 and VEGF expression might provide additional information about tumor features.

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Intra‐tumoral interleukin‐6 down‐regulation system and genetic mutations of tumor suppressor genes in colorectal carcinoma

Cited by 28 publications

References 27 publications

Does Postoperative Serum Interleukin-6 Influence Early Recurrence after Curative Pulmonary Resection of Lung Cancer?

Does Postoperative Serum Interleukin-6 Influence Early Recurrence after Curative Pulmonary Resection of Lung Cancer?

Preoperative interleukin‐6 production by mononuclear blood cells predicts survival after radical surgery for colorectal carcinoma

Interleukin-17 may be a valuable serum tumor marker in patients with colorectal carcinoma

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