Correlation of Decreased Survival and IL-18 in Bone Metastasis

Okamoto, Masaki; Azuma, Koichi; Hoshino, Tomoaki; Imaoka, Haruki; Ikeda, Jirō; Kinoshita, Takashi; Takamori, Shinzo; Ohshima, Koichi; Edakuni, Nobutaka; Kato, Seiya; Iwanaga, Tomoaki; Aizawa, Hisamichi

doi:10.2169/internalmedicine.48.1851

Cited by 17 publications

(15 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8 Nonetheless, IL-18 is not specific for ovarian cancer, since it has been found elevated in other neoplastic conditions, such as gastric, 22 head and neck, 23 breast, 24,25 renal 33 and lung 34 cancers. Here, we show that increased IL-18 serum levels are found in some EC patients, although the average IL-18 levels in a small cohort of these patients were not significantly elevated.…”

Section: Discussionmentioning

confidence: 99%

Interleukin (IL)‐18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor

Orengo

Fabbi

Miglietta

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

Interleukin (IL)-18 is a proinflammatory and immune-enhancing cytokine, which exerts antitumor effects in vivo, mediated by the induction of interferon (IFN)c. We previously reported that IL-18 processing is defective in epithelial ovarian carcinoma (EOC) cells, which secrete an inactive precursor (pro-IL-18) in vitro. In addition, IL-18 was reported as a potential biomarker of EOC. Here, we further investigated its role as a serological marker in human EOC and addressed its possible biological activity in vivo. Our data indicate that immunoreactive IL-18 is increased in EOC patients' sera at diagnosis as compared with age-matched healthy women. IL-18 levels were higher in the ascitic fluids than in sera, suggesting a local production in the peritoneal cavity. Indeed, immunohistochemical analysis of tumors showed IL-18 expression in cytokeratine-positive neoplastic cells, although also scattered histiocytes and some lymphoid cells stained for IL-18. The detection of human IL-18 in sera and ascitic fluids of immunodeficient mice, orthotopically implanted with human EOC cells, further suggested that circulating IL-18 is tumor-derived. However, IL-18 is not an EOC specific biomarker, as increased serum levels were found also in some endometrial cancer patients. By means of a new monoclonal antibody, we characterized IL-18 present in the ascitic fluid as pro-IL-18, which is biologically inactive. Accordingly, IFNc was not increased in EOC patients' sera and ascitic fluids and showed no correlation with IL-18 levels. Altogether these data indicate that IL-18 in EOC fluids is predominantly tumor-derived and that its lack of biological activity may represent a mechanism of tumor-escape.

show abstract

Section: Discussionmentioning

confidence: 99%

Interleukin (IL)‐18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor

Orengo

Fabbi

Miglietta

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Serum IL-18 negatively associated with overall survival in small cell lung cancer (NSCLC). Serum IL-18 levels were significantly higher in NSCLC with metastasis than in NSCLC without metastasis (Okamoto et al, 2009). …”

Section: Figure 1 Mechanism Of Immune Suppression By Il-18mentioning

confidence: 90%

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Kuppala¹,

Syed²,

Bandaru³

et al. 2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. It plays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidate in gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) in patients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individual cytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinational effects of cytokines with IL-18 in cancer progression. IL-18 is an important non-invasive marker suspected of contributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor of survival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applications for chemotherapy and prognostic or diagnostic significance.

show abstract

“…Still, serum IL-18 levels of breast cancer patients with bone metastases were statistically significantly higher, compared to those of breast cancer patients with other organ metastases. [7,9] Following the important discovery that primary osteoblasts can also secrete IL-18 receptor components, many authors have suggested that osteoblasts are target cells in IL-18 response and that IL-18 exerts a physiological effect on osteogenic cells. [10] IL-18 exerts its effects on osteoblasts, not via production of INF-y, but rather via production of granulocyte macrophage colony-stimulating factor (GM-CSF).…”

Section: Discussionmentioning

confidence: 99%

Relationship Between IL-18 and Bone Metastasis in Female Breast Cancer

Nayır¹

2016

TJ Oncol

View full text Add to dashboard Cite

OBJECTIVEBreast cancer is a metastatic disease that frequently (in approximately 70% of cases) affects the skeletal system. The aim of the present study was to compare serum IL-18 levels in breast cancer patients with and without bone metastases with healthy controls. METHODSIncluded were a total of 154 female breast cancer patients with bone metastases (n=53; Group 2) and without bone metastases (n=51; Group 1), as well as 50 healthy control subjects (Group 3). Serum IL-18 levels were compared among the groups. RESULTSMean serum IL-18 levels were significantly different between Groups 1 and 3 (p<0.001), Groups 2 and 3 (p<0.001), and Groups 2 and 1 (p=0.020). In receiver operating characteristic (ROC) curve analysis performed between Groups 1 and 2, sensitivity of serum IL-18 levels in patients with bone metastases was nearly 26 percent. CONCLUSIONLower rates of IL-18 sensitivity were detected in breast cancer patients with bone metastasis.

show abstract

Correlation of Decreased Survival and IL-18 in Bone Metastasis

Abstract: Objective Previous studies have reported that serum

Cited by 17 publications

References 38 publications

Interleukin (IL)‐18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor

Interleukin (IL)‐18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Relationship Between IL-18 and Bone Metastasis in Female Breast Cancer

Contact Info

Product

Resources

About