Jiro Honda

Enhancement of Human Cancer Cell Motility and Invasiveness by Anaphylatoxin C5a via Aberrantly Expressed C5a Receptor (CD88)

Purpose: The anaphylatoxin C5a is a chemoattractant that induces leukocyte migration via C5a receptor (C5aR). There is emerging evidence that C5a is generated in the cancer microenvironment. We therefore sought C5aR expression and a direct influence of the C5a–C5aR axis on cancer cells. Experimental Design: C5aR expression was investigated in human cancer tissues and cell lines. Effects of C5a stimulation on cancer cells were studied by cytoskeletal rearrangement, time-lapse analysis, Matrigel chamber assay, and invasion in nude mouse in a comparison of C5aR-expressing cancer cells with control cells. Results: C5aR was aberrantly expressed in various human cancers. Several cancer cell lines also expressed C5aR. C5a triggered cytoskeletal rearrangement and enhanced cell motility three-fold and invasiveness 13-fold of C5aR-expressing cancer cells. Such enhancement by C5a was not observed in control cells. Cancer cell invasion was still enhanced in the absence of C5a concentration gradient and even after the removal of C5a stimulation, suggesting that random cell locomotion plays an important role in C5a-triggered cancer cell invasion. C5a increased the release of matrix metalloproteinases (MMP) from cancer cells by two- to 11-fold, and inhibition of MMP activity abolished the C5a-enhancing effect on cancer cell invasion. Compared with control cells, C5aR-expressing cells spread 1.8-fold more broadly at implanted nude mouse skin sites only when stimulated with C5a. Conclusions: These results illustrate a novel activity of the C5a–C5aR axis that promotes cancer cell invasion through motility activation and MMP release. Targeting this signaling pathway may provide a useful therapeutic option for cancer treatment. Clin Cancer Res; 19(8); 2004–13. ©2013 AACR.

Mass screening for prostate cancer in patients with end‐stage renal disease: a comparative study

To determine the usefulness of prostate‐specific antigen (PSA) screening for prostate cancer in patients with end‐stage renal disease (ESRD), as although serum PSA is effective in the early detection of this cancer in the general population, there are few reports of its utility in patients with ESRD.

Severe bleeding tendency caused by a rare complication of excessive fibrinolysis with disseminated intravascular coagulation in a 51-year-old Japanese man with prostate cancer: a case report

IntroductionDisseminated intravascular coagulation causes thrombotic tendency leading to multiple organ failure and occurs in a wide variety of diseases including malignancy. Disseminated intravascular coagulation is a latent complication in people with prostate cancer.Case presentationA 51-year-old Japanese man with advanced castration-resistant prostate cancer was admitted to our hospital because of extensive purpura and severe anemia. Prolonged plasma coagulation time, hypofibrinogenemia and normal platelet count suggested that a decrease in fibrinogen induced a bleeding tendency causing purpura. However, elevated plasma levels of thrombin-antithrombin complex, fibrin and/or fibrinogen degradation products and D-dimers, with positive fibrin monomer test, manifested disseminated intravascular coagulation and subsequent fibrinolysis. Plasma levels of thrombin-antithrombin complex, fibrin and/or fibrinogen degradation products and D-dimers decreased after administration of low-molecular-weight heparin. However, low fibrinogen and α2-antiplasmin levels were not improved and plasmin-antiplasmin complex did not decrease, which revealed excessive fibrinolysis complicated with disseminated intravascular coagulation. We suspected that prostate cancer cell-derived urokinase-type plasminogen activator caused excessive fibrinolysis. Administration of tranexamic acid for fibrinogenolysis was added together with high-dose anti-androgen therapy (fosfestrol) for prostate cancer. Thereafter, prostate-specific antigen and plasmin-antiplasmin complex decreased, followed by normalized fibrinogen and α2-antiplasmin levels, and the patient eventually recovered from the bleeding tendency. Immunohistochemical staining of the biopsied prostate tissue exhibited that the prostate cancer cells produced tissue factor, the coagulation initiator, and urokinase-type plasminogen activator.ConclusionThis patient with rare complications of disseminated intravascular coagulation and excessive fibrinolysis is a warning case of potential coagulation disorder onset in patients with prostate cancer. We propose that combined administration of tranexamic acid and low-molecular-weight heparin together with high-dose anti-androgen therapy is a useful therapeutic option for patients with this complicated coagulation disorder.

Lower urinary tract dysfunction in type 1 familial amyloidotic polyneuropathy in Kumamoto, Japan.

Objective: To evaluate lower urinary tract dysfunction of type 1 familial amyloidotic polyneuropathy (FAP) patients in Kumamoto, Japan.

Regional differences in the functional and biochemical properties of endothelin receptor subtypes in the rabbit prostatic urethra.

To examine the regional differences in the functional (pharmacological) and biochemical properties of endothelin (ET) receptors in the rabbit prostatic urethra.

Neurologic toxicity associated with interferon α therapy for renal cell carcinoma

Abstract  A 67‐year‐old man received interferon α (IFN α) therapy for lung metastases of renal cell carcinoma (RCC). Multiple pulmonary metastases disappeared completely. However, neurological toxicity was detected by magnetic resonance imaging (MRI) as abnormal brain lesions. After discontinuation of IFN α therapy, his neurological symptoms and abnormal lesions on MRI disappeared completely. Complete remission of RCC has continued, and results of neurological study have remained normal for 5 years after discontinuation of IFN α therapy.

Renal Carcinoma Surveillance Counterpoint: Japan

Huang et al. provide an excellent summary of contemporary renal cell carcinoma management, including the epidemiology, diagnosis, surgical treatment, systemic therapy, and strategies for follow-up [1]. We present our opinion, which slightly differs from that of Huang et al., based on recent reports and our experience at Kyushu University, Japan.