Clinical implications of expression of interleukin-8 related to myometrial invasion with angiogenesis in uterine endometrial cancers

Fujimoto, Jiro; Aoki, Ikumi; Khatun, Sufia; Toyoki, Hiroshi; Tamaya, Teruhiko

doi:10.1093/annonc/mdf078

Cited by 126 publications

(135 citation statements)

References 18 publications

Supporting

Mentioning

129

Contrasting

Order By: Relevance

“…In other clinical studies, resistin have been associated with inflammatory markers apparently independent on BMI, but related to risk factors of atherosclerosis [31,32]. Together with facts that up-regulated pro-inflammatory cytokines and chemokines in tumors [33][34][35] and inflammation itself is recently recognized as risk factor contributing on cancer development and progression [36][37][38][39], resistin seems to be a novel secreted protein in relation to inflammation in humans and may present molecular link between inflammation and carcinogenesis.…”

Section: Discussionmentioning

confidence: 81%

Relationship of resistin levels with endometrial cancer risk

Hlavna

Kohut²,

Lipková³

et al. 2011

neo

View full text Add to dashboard Cite

Cancer of endometrium (CAE) is the most common gynecologic malignancy in industrialized nations. Increased resistin levels, an adipocytokine produced by adipose tissue and macrophages, have been considered as a risk factor in gastric, colon and breast cancer, recently. No studies associating resistin levels with endometrial cancer have been done so far. The purpose of this case-control study was to determine the relationship between serum circulating resistin levels and resistin gene -420C>G (rs3219175) variant in endometrial cancer patients. 37 Caucasian female patients and 39 healthy controls were enrolled in this study. Difference in resistin levels between age and BMI matched patients group (mean 24.2 ng/ml) and control subjects (mean 10.1 ng/ml) were statistically significant (p < 0.01). We also determined single nucleotide polymorphism -420C>G (rs3219175) within resistin gene and no significant association between resistin levels and investigated polymorphism was found. Furthermore, no significant association between higher resistin levels and diabetes mellitus 2, body mass index, smoking or age have been observed within studied groups. To our knowledge, this is the first study examining the relationship between serum resistin levels and endometrial cancer and our results show, that patients with endometrial cancer have significantly increased circulating levels of resistin compared to control subjects.

show abstract

Section: Discussionmentioning

confidence: 81%

Relationship of resistin levels with endometrial cancer risk

Hlavna

Kohut²,

Lipková³

et al. 2011

neo

View full text Add to dashboard Cite

show abstract

“…It has been shown to correlate with poor prognosis in carcinomas of the breast (37,38), cervix (39,40), and bladder (41), confirming to some extent the protumorigenic role of macrophages. On the other hand, macrophages in stomach cancer were associated with good prognosis of the disease (42), and there has been varying results with lung cancer (43,44).…”

Section: Discussionmentioning

confidence: 88%

Effects of cytokine-induced macrophages on the response of tumor cells to banoxantrone (AQ4N)

Mehibel

Singh

Chinje

et al. 2009

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Tumor-associated macrophages (TAMs) are found in many solid tumors and have often been shown to accumulate in the hypoxic regions surrounding areas of necrosis. TAMs are the major site of expression of nitric oxide synthase (NOS), a heme-containing homodimeric enzyme consisting of oxygenase and reductase domains. The latter has a high degree of sequence homology to cytochrome P450 reductase and a functional consequence of this is the ability of NOS, under hypoxic conditions, to activate the bioreductive drugs tirapazamine and RSU1069. Banoxantrone (AQ4N) is a bioreductive prodrug activated in hypoxia by an oxygen-dependent two-electron reductive process to yield the topoisomerase II inhibitor AQ4. A feature of this process is that the final product could potentially show bystander cell killing. Thus, in this study, we investigated the ability of inducible NOS (iNOS)-expressing TAMs to activate AQ4N and elicit toxicity in cocultured human tumor cells. Murine macrophages were induced to overexpress iNOS by treatment with a combination of cytokines, mixed with HT1080 and HCT116 human tumor cells, and the toxicity of AQ4N was determined under aerobic or hypoxic conditions. The aerobic toxicity of AQ4N toward tumor cells was not affected through coculturing with macrophages. However, under hypoxic conditions, the induction of iNOS activity in the macrophages was associated with an increase in AQ4N metabolism and a substantial increase in tumor cell toxicity, which was dependent on the proportion of macrophages in the culture. This study is the first demonstration of TAM-mediated prodrug activation to result in bystander killing of human tumor cells.

show abstract

“…The prognosis of the 20 patients with high IL-8 in uterine cervical cancers was extremely poor, whereas the 24-month survival rate of the other 60 patients with low IL-8 was 67%. Therefore, this indicates that IL-8 is a prognostic indicator as an angiogenic factor supplied from macrophages within and around the tumor [12]. Basic FGF levels were higher in advanced primary uterine cervical cancers, regardless of histological type.…”

Section: Introductionmentioning

confidence: 80%

“…Specific angiogenic factors produce specific angiogenesis in each tumor. The angiogenic factors vascular endothelial growth factor (VEGF) [2][3][4][5][6], thymidine phosphorylase (TP) identified with platelet-derived endothelial cell growth factor [7][8][9][10][11], interleukin (IL)-8 [12,13], and basic fibroblast growth factor (bFGF) [14][15][16] along with the angiogenic transcription factor ETS-1 [17][18][19][20] work on angiogenesis in gynecological cancers, especially in uterine cervical cancer [2, 3, 7-9, 12, 14, 17] as follows.…”

Section: Introductionmentioning

confidence: 99%