Terukazu Nakamura

Quantitative analysis of macrophage inhibitory cytokine-1 (MIC-1) gene expression in human prostatic tissues

Macrophage inhibitory cytokine-1 (MIC-1) gene is a member of transforming growth factor-β superfamily and was reported to be highly overexpressed in human prostate cancer using microarray technology. The aim of this study was to evaluate the quantitative expression of MIC-1 in malignant and benign prostate tissues and to associate expression levels with clinicopathological parameters of prostate cancer. Matched (paired) prostatic tissue samples from the cancerous and noncancerous parts of the same prostates were obtained from 66 patients who underwent radical prostatectomy. Quantitative RT–PCR was performed using SYBR Green I on the Roche LightCyclerTM system. Macrophage inhibitory cytokine-1 gene overexpression in cancerous tissues was observed in 88% of cases, compared to noncancerous tissues (P<0.001). The expression level of MIC-1 in cancerous tissues was significantly higher than in noncancerous tissue (P<0.001). Higher expression of MIC-1 gene was significantly associated with higher Gleason score (P=0.004). The expression of the MIC-1 gene in prostate cancer is significantly higher than in noncancerous tissues, especially in more aggressive forms of the disease (Gleason score>5). This is in contrast to prostate-specific antigen that is downregulated in higher-grade tumours. The upregulation of MIC-1 in prostate cancer and in advanced and more aggressive prostatic tumours suggests that MIC-1 protein should be evaluated as a potential diagnostic and prognostic biomarker.

Quantitative Analysis of Kallikrein 15 Gene Expression in Prostate Tissue

PURPOSE The newly discovered human kallikrein 15 gene KLK15 has been shown in preliminary analysis to be associated with more aggressive types of prostate cancer. We quantitatively measured and compared gene expression of KLK15 in malignant and benign prostate tissues. MATERIALS AND METHODS Matched prostate tissue samples from the cancerous and noncancerous parts of the same prostates were obtained from 90 patients who underwent radical prostatectomy. Quantitative reverse transcriptase-polymerase chain reaction using SYBR Green I and the LightCycler system (Roche Applied Science, Mannheim, Germany) was performed. Associations of KLK15 expression with clinicopathological parameters were analyzed. RESULTS KLK15 over expression in cancerous versus noncancerous tissue was found in 76 of the 90 patient samples (84.4%, p <0.001). The ratio of cancerous-to-noncancerous KLK15 expression tended to be higher in patients with stage pT3/4 versus pT2 tumors (p = 0.1). KLK15 expression tended to be higher in grade 3 than in grade 2 tumors and in Gleason score 7 or greater than in Gleason score less than 7 tumors (p = 0.18 and 0.23, respectively). A 1.7 cutoff at the 40th percentile provided a significant difference in stages pT2 and pT3/4 tumors (p = 0.029). CONCLUSIONS On quantitative real-time polymerase chain reaction KLK15 expression was significantly higher in cancerous than in noncancerous tissue. Up-regulation of the KLK15 gene in advanced and more aggressive tumors may indicate a possible role for KLK15 protein as future serum marker for prostate cancer and for distinguishing tumor aggressiveness.

Quantitative analysis of hippostasin/KLK11 gene expression in cancerous and noncancerous prostatic tissues

OBJECTIVES Hippostasin/kallikrein 11 (KLK11) is a member of the human kallikrein gene family, which includes prostate-specific antigen (PSA), human kallikrein 2 (hK2), and another 12 members, all localized on chromosome 19q13.4. Hippostasin has two alternative splicing isoforms, known as the brain type and prostate type. We have previously reported that the prostate-type isoform is not expressed in human prostate cancer cell lines. METHODS We compared the expression of hippostasin/KLK11 isoforms in 76 matched pairs of human normal and prostate cancer tissues by quantitative reverse transcriptase-polymerase chain reaction. RESULTS The expression of both isoforms of KLK11 was 25% to 45% higher in cancer tissues compared with their normal counterparts. Regarding prostate-type KLK11, we identified a significant association between lower expression and higher tumor stage, Gleason score, and tumor grade. No such association was seen with the brain-type isoform. CONCLUSIONS : The expression of the prostate-type isoform of KLK11 is increased in prostate cancer. This parameter should be examined further as a new prognostic indicator of prostate cancer.

Serum human glandular kallikrein 2 (hK2) for distinguishing stage and grade of prostate cancer

Background:  Human glandular kallikrein (hK2) has been shown to add important information regarding the early detection and staging of prostate cancer. Preliminary analysis pointed out that hK2 may discriminate between pT2 and pT3 tumors, and that hK2 may predict Gleason grade 4/5 cancer volume, better than prostate‐specific antigen (PSA) or percent free PSA (% fPSA). We investigated the role of hK2 serum values for predicting pathological stage, grade and Gleason score.

Radio‐frequency ablation of renal cell carcinoma in patients who were at significant risk

Abstract  Objective:  Although radio‐frequency ablation (RFA) has been recently applied as a minimally invasive treatment option for renal cell carcinoma (RCC), indication of this modality remains a critical issue due to the lack of complete tumor destruction as well as the uncertainty of its long‐term efficacy. We report the efficacy of RFA for nine carefully selected patients with RCC who had significant reason to avoid invasive surgical treatment under general anesthesia.

Radiofrequency ablation for renal tumors : Our experience

Objectives:  To report our results of percutaneous radiofrequency ablation (RFA) for renal tumors and to assess predictors of therapeutic efficacy.

Improved prostate cancer detection with a human kallikrein 11 and percentage free PSA-based artificial neural network

Abstract Human kallikrein 11 (hK11) was evaluated in a percentage free PSA-based artificial neural network (ANN) to reduce unnecessary prostate biopsies. Serum samples from 357 patients with (n=132) and without (n=225) prostate cancer (PCa) were analyzed and ANN models were constructed and compared to all parameters. The discriminatory power of hK11 was lower than that of PSA, but receiver operator characteristic (ROC) analyses demonstrated significantly larger areas under the curves for the ANN compared to all other parameters. ANNs with hK11 may lead to a further reduction in unnecessary prostate biopsies, especially when analyzing patients with less than 15% free PSA.

Brain metastases from testicular germ cell tumors: A retrospective analysis

Objectives:  To review our series of testicular germ cell tumors with brain metastases and to establish an optimal treatment strategy for them.

Recent strategy for the management of advanced testicular cancer

Testicular cancer is the most common cancer in young men and the cure rate has been approximately 80% since the introduction of cisplatin in the 1970s. BEP therapy (including bleomycin, etoposide and cisplatin) has become a standard induction therapy instead of PVB therapy (cisplatin, vinblastin and bleomycin). However, the patients with incomplete responses to cisplatin‐based first‐line therapy or with relapsed disease have an extremely poor prognosis. For such difficult‐to‐treat patients, there are some proposed treatment options such as ifosfamide‐containing salvage chemotherapy or high‐dose chemotherapy (HDCT). HDCT with bone marrow rescue has been carried out as salvage or induction chemotherapy. However, a randomized control trial did not show the superiority to conventional first line therapy or salvage therapy. Therefore, a new anticancer agent was tested for cisplatin‐refractory or resistant testicular cancer. The development of combination therapy with new anticancer agents such as paclitaxel and irinotecan seems to be effective for these patients. TIP therapy including paclitaxel, ifosfamide and cisplatin would be a standard second line therapy for the patients with BEP failure. Residual tumor resection including retroperitoneal lymph node dissection integrated with induction and salvage chemotherapy still remains to play an important role to achieving a cure for advanced testicular cancer because there is no modality to predict residual viable cancer cells or teratoma element in the residual tumors. In the present review, we discuss and focus on the recent treatment strategy of advanced testicular cancer.

Efficacy of Goshajinkigan for Oxaliplatin-Induced Peripheral Neuropathy in Colorectal Cancer Patients

Objective. To evaluate the efficacy of Goshajinkigan for oxaliplatin-induced peripheral neuropathy in colorectal cancer patients. Patients. Colorectal cancer patients (N = 29) who received ≥4 weeks of Goshajinkigan for oxaliplatin-induced peripheral neuropathy during chemotherapy at Kyoto Prefectural University of Medicine were (Goshajinkigan group) compared to 44 patients who had not received Goshajinkigan during the same period (non-Goshajinkigan group). Main Outcome Measures. The effect of Goshajinkigan was graded as curative, effective, stabilizing, or deleterious. The relationships between the grade of peripheral neuropathy and the dose of oxaliplatin in the Goshajinkigan and non-Goshajinkigan groups were evaluated. Results. The effect of Goshajinkigan on peripheral neuropathy in the Goshajinkigan group was curative, effective, stabilizing, and deleterious in 3.4, 20.7, 69.0, and 6.9% of patients, compared to the effect in the non-Goshajinkigan group (4.5, 15.9, 45.5, and 34.1%). The ratio of deleterious effects was significantly different between these two groups (P = 0.04). A Kaplan-Meier analysis in relation to the cumulative dose of oxaliplatin showed that the incidence of grade 3 peripheral neuropathy tended to be less in the Goshajinkigan group (P = 0.05). There were no significant differences in time to treatment failure and severe adverse events between these two groups. Conclusions. Goshajinkigan prevented exacerbation of oxaliplatin-induced peripheral neuropathy. This trial is registered with UMIN000009956