Is inflammation related to any diseases? I asked this question when I read the Review and Original Articles in this issue.
Carcinogenesis as a result of inflammation has been noted in stomach cancer in relation to Helicobacter pylori, liver cancer as a result of hepatitis virus, and, in the urological field, squamous bladder cancer linked to schistosomiasis. The Review Article by Nakai and Nonomura (Osaka, Japan) described the inflammation in normal prostate and prostate cancer tissues in relation to the initiation of prostate cancer. Proliferative inflammatory atrophy (PIA) is known to be associated with acute or chronic inflammation in the peripheral zone where prostate cancer predominantly develops. PIA might link inflammation and cancer. In an epidemiological view, a fat-rich diet is a risk factor of prostate cancer. Grilled meats produce heterocyclic amine and polycyclic aromatic hydrocarbons. These compounds induce inflammation of prostate tissues. Xenobiotics have received attention because of their estrogenic effects that might cause hypospadias and other congenital abnormalities. The role of estrogen in the initiation and the progression of prostate cancer will be further investigated.
Does inflammation accelerate cancer progression? Patients with advanced cancer are associated with high fever and/or inflammatory reactions. Is inflammation the cause or the result of cancer progression? C-reactive protein (CRP) is widely used as a biomarker to monitor whole-body inflammation. Saito and Kihara (Tokyo, Japan) reviewed the role of CRP in urological cancers. CRP is a valuable prognosis factor that can be used in ordinary practice. CRP is generally produced by hepatocytes through the stimulation of cytokines including interleukin (IL)-6 and IL-1β. These cytokines play an important role, because they work as autocrine and/or paracrine growth factors in the cancer microenvironment. Therefore, CRP is not the cause of cancer progression, but the result of cytokines produced by cancer or immunological cells. Then, how are theses cytokines produced? For example, IL-6 is induced by the activation of transcription factors including NF-κB. However, the mechanism underlying NF-κB activation is diverse. Further investigation should be focused on why the inflammatory reaction is common in predicting the poor prognosis of all malignancies.
A cancer microenvironment composed of cancer and mesenchymal cells can be conceived as an inflammatory environment where hematological cells target or help cancer cells. Choi et al. (Ansan, Korea) have shown CD74 expression in the microenvironment. CD74 is part of a receptor complex for macrophage migration inhibitory factor (MIF). They found that CD74 expression is increased in high-grade invasive bladder cancer. This implicates the immunological escape of cancer cells. Indeed, CD74 expression was correlated with the absence of tumor-infiltrating inflammatory cells and the presence of tumor-associated inflammatory cells. Milatuzumab is a humanized anti-CD74 antibody being evaluated for hematological malignancies. This study might have opened the gate for molecular-targeted therapy for invasive bladder cancer where no such agents are available at present.
How do we treat inflammation? The answer depends on the disease that induced inflammation. Interstitial cystitis (IC) is a refractory inflammatory disease, the cause of which is unknown. Wada et al. (Hokkaido, Japan) have shown the effect of intrathecal administration of E-series prostaglandin 1 (EP1) receptor antagonist in a cyclophosphamide-induced cystitis rat model. EP-1 receptor antagonist is promising for future therapy. Another treatment strategy for IC comes from focusing on the defective urothelial lining in the bladder. The pathogenesis of IC involves the mucin glycosaminoglycan layer of the urothelium. Hyaluronic acid (HA) is a relevant component. Lai et al. (Taipei, Taiwan) showed the result of a comparative randomized trial to determine the optimization of the regimens, namely, four weekly intravesical instillations of 40 mg of HA followed by monthly instillations or 12 intravesical instillations every 2 weeks. Both groups had no differences in showing a significant improvement in symptom scores and Quality of Life Index.