Go Kimura

Expression of insulin-like growth factor (IGF)-II in human prostate, breast, bladder, and paraganglioma tumors.

Abstract Insulin-like growth factors (IGFs) are potent mitogens for a variety of cancer cells in vitro. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. Information on cell-type-specific IGF-II expression in vivo in the breast and prostate is, however, limited. Thus, cell types expressing IGF-II mRNA and protein in tumors were identified by in situ hybridization and immunohistochemistry. Of 36 prostate, 17 breast, and 10 bladder cancers, and 9 paraganglioma tissues examined, IGF-II was expressed in more than 50% of prostate, breast, and bladder tumors, and in 100% of paraganglioma tumors. Expression levels of IGF-II were highest in the paraganglioma and bladder followed by prostate and breast tumors. In all the tumors expressing IGF-II, both mRNA and protein were localized to malignant cells, expression in the stroma being minimal. Since previous studies had indicated that an incompletely processed form of 15-kDa IGF-II exhibited higher mitogenic potency than the completely processed 7.5-kDa IGF-II form, the quantity and size of IGF-II proteins expressed in these tumors were analyzed by Western immunoblotting. Greater expression of 15-kDa IGF-II relative to the 7.5-kDa IGF-II form was clearly demonstrated in all six prostate cancers and in half of the two breast and four bladder cancers examined. The results are consistent with the hypothesis that the 15-kDa form of IGF-II expressed in cancerous cells contributes to autocrine cancer cell growth in vivo.

Clinical evaluation of soluble cytokeratin 19 fragments (cyfra 21-1) in serum and urine of patients with bladder cancer

OBJECTIVES CYFRA 21-1 is a new tumor marker that measures cytokeratin 19 (CK-19) fragments by a sandwich enzyme-linked immunosorbent assay (ELISA). In this study, we evaluated the usefulness of serum and urine CYFRA 21-1 as a tumor marker for bladder cancers. METHODS We measured serum and urine CYFRA 21-1 levels in a group of patients with bladder cancer (n = 58) and a group without bladder cancer (n = 220). The latter group was divided into five subgroups of patients (those with cystitis, benign prostatic hyperplasia (BPH), urolithiasis, or renal dysfunction, and a group of healthy, controls). In the bladder cancer group, we measured CYFRA 21-1 levels after transurethral resection of bladder tumor (TUR-Bt), and we also analyzed the relationship between serum and urine CYFRA 21-1 levels and tumor-related factors. RESULTS Serum and urine CYFRA 21-1 levels were significantly higher in the bladder cancer group than in each of the non-bladder cancer subgroups. However, urine CYFRA 21-1 levels did not differ significantly between the bladder cancer group and the cystitis subgroup. In the bladder cancer group, serum CYFRA 21-1 levels were significantly higher in patients with local advanced-stage tumors and in those who had metastases. Urine CYFRA 21-1 levels decreased as a function of time after TUR-Bt. These levels were strongly correlated with tumor volume and were significantly better than urine cytology for the detection of bladder cancers of grades 1 and 2. CONCLUSIONS These results suggest that urine CYFRA 21-1 is a useful tumor marker in screening for bladder cancer, and that serum CYFRA 21-1 may be a tumor marker for advanced bladder cancers.

Prevalence of renal cell carcinoma: A nation-wide survey in Japan, 2002

Objective:  To investigate the incidence of renal cell carcinoma, classified by sex, age group and region in Japan, following a 5‐year interval after a previous survey performed in 1997.

Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer : Extended Analysis of the Phase 3 PREVAIL Study

Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28-0.37; p<0.0001) and the risk of death by 23% (HR 0.77, 95% CI 0.67-0.88; p=0.0002). Median investigator-assessed rPFS was 20.0 mo (95% CI 18.9-22.1) in the enzalutamide arm and 5.4 mo (95% CI 4.1-5.6) in the placebo arm. Median OS was 35.3 mo (95% CI 32.2-not yet reached) in the enzalutamide arm and 31.3 mo (95% CI 28.8-34.2) in the placebo arm. At the time of the OS analysis, 167 patients in the placebo arm had crossed over to receive enzalutamide. The most common adverse events in the enzalutamide arm were fatigue, back pain, constipation, and arthralgia. This final analysis of PREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PREVAIL is registered on ClinicalTrials.gov as NCT01212991. PATIENT SUMMARY According to data from longer follow-up, enzalutamide continued to provide benefit over placebo in patients with metastatic castration-resistant prostate cancer.

Tumor progression and expression of matrix metalloproteinase-2 (MMP-2) mRNA by human urinary bladder cancer cells

Abstract Tumor cells at the stage of tumor progression build up a high tolerance to intrinsic and extrinsic defence systems and/or therapeutic procedures, and the cells deeply infiltrate the adjacent tissue, which is followed by tumor metastasis to remote organs and tissues. This study was designed to investigate the relationship between expression of matrix metalloproteinase-2 (MMP-2) and invasiveness of human bladder cancer cells, using cell lines derived from a parental human urinary bladder tumor cell line, T24. Two subpopulations of the human bladder cancer cell line T24, Hi-T24 and Lo-T24, were selected using an invasion assay and then expression of MMP-2 mRNA and protein was analyzed by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme immunoassay (EIA). The gross morphology, cell growth rate, and adhesion activity to a basement membrane extract (matrigel) of the high-invasive Hi-T24 cells were similar to those of the low-invasive Lo-T24 cells, but the Hi-T24 cells were 3.8-fold more haptotactic through matrigel than the Lo-T24 cells. The haptotactic activity of the Hi-T24 cells was suppressed by the addition of an anti-MMP-2 antibody, and the amounts of MMP-2 protein secreted into the spent medium by the Hi-T24 and Lo-T24 cells were 7.8 ± 0.2 and 3.8 ± 0.3 ng/ml (P < 0.05), respectively. The quantities of tissue inhibitor of metalloproteinase-2 (TIMP-2) protein secreted by Hi-T24 and Lo-T24 cells were 133.2 ± 4.3 and 168.7 ± 5.6 ng/ml, respectively (P < 0.05). The levels of transcription of the genes encoding MMP-2 and the transmembrane MMP, MT-MMP, evaluated by RT-PCR, were higher in the Hi-T24 cells than in the Lo-T24 cells. Expression of the TIMP-2 gene was slightly lower in the Hi-T24 cells than in the Lo-T24 cells. These results indicate that expression of the metalloproteinases are imbalanced at the gene level in human urinary bladder cancer cells at the stage of tumor progression.

High-frequency endoluminal ultrasonography for staging transitional cell carcinoma of the bladder

OBJECTIVES To assess the feasibility and limitations of endoluminal ultrasound (ELUS) for clinical staging of bladder tumors. METHODS From 1998 to 1999, 32 patients with transitional cell carcinoma of the bladder were evaluated by high-frequency ELUS using miniature ultrasound transducers (20 MHz, 5.1F or 7.2F) before transurethral resection. Clinical staging using ELUS was compared with the results of pathologic staging. RESULTS Seventeen (94%) of the 18 patients with superficial tumors on ELUS were confirmed by pathologic examination to have Stage pTa (n = 12) or Stage pT1 (n = 5) disease, and 11 (63%) of the 14 patients with muscle-invasive tumors on ELUS were confirmed by pathologic evaluation to have Stage pT2a (n = 2) or Stage pT2b (n = 9) disease. In all of the misdiagnosed patients, the tumor lacked a well-defined base and was larger than 2 cm in size. It was difficult to distinguish between Stage Ta and Stage T1 tumors because of the limited resolution of ELUS and between Stage T2a and Stage T2b tumors because of its low penetration. CONCLUSIONS ELUS using a high-frequency (20 MHz), miniature ultrasound transducer is able to distinguish superficial tumors from those with muscle invasion. However, the lack of penetration of the sonographic beam places major limitations on the evaluation of the depth of the invasion in large (greater than 2 cm) tumors with a broad base.

Comparison of urine cytology between the ileal conduit and Indiana pouch

OBJECTIVE To compare the cytomorphologic features of urine obtained from two different kinds of urinary diversions constructed after total bladder resection. STUDY DESIGN The smears of urine from 11 ileal conduits and 6 Indiana pouches were evaluated. All patients underwent total bladder resection due to transitional cell carcinoma (TCC) or other kinds of cancer before urine diversion. RESULTS The cytologic features of Indiana pouch urine include degenerated, small, round cells without columnar cells derived from intestinal epithelium. In ileal conduit urine, well-preserved columnar cells and degenerated, small, round cells were frequently observed. The columnar cells in ileal conduit urine exhibited cytologic features that should be distinguished from TCC cells. CONCLUSION The method of reconstructing the urinary tract is important in urine cytology from urine diversions because the cytomorphologic features of urine are different between the two kinds of urinary diversions. Since columnar cells in ileal conduit urine might lead to misdiagnosis as TCC, special consideration is required to examine ileal conduit urine.

Renal masses detected by general health checkup.

Abstract Background A total of 60 604 persons underwent a general health checkup at Toma Hospital, Saitama, Japan, between January 1993 and June 1997, and transabdominal ultrasonography (US) was performed on all persons. We investigated the usefulness of transabdominal US in detecting renal tumors during general health checkups.

Antitumour effects of the angiogenesis inhibitor AGM-1470 on rat urinary bladder tumours induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.

To examine the antitumour effects of the angiogenesis inhibitor AGM‐1470 (TNP‐470) on rat urinary bladder tumours induced by N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine (BBN).

Use of Targeted Therapies for Advanced Renal Cell Carcinoma in the Asia-Pacific Region: Opinion Statement From China, Japan, Taiwan, Korea, and Australia

Rates of renal cell carcinoma (RCC) morbidity and mortality vary widely by geography, with increasing incidence in most countries. Interestingly, RCC incidence is significantly lower in Asian countries relative to other regions, which is attributed to environmental and genetic influences. Additionally, it has been demonstrated that different ethnic groups differ in their RCC characteristics which might lead to varied responses to therapy. In this review, physicians drawn from countries across the Asia-Pacific region--China, Japan, Taiwan, Republic of Korea, and Australia--take all available data into consideration to develop the first opinion statement on treatment of advanced RCC in the region. We have sought to determine what factors influence treatment patterns and availability of therapeutic agents in our respective countries, discussed whether these factors are fully justified or should be modified, and considered what additional efforts should be undertaken to optimize treatment outcomes in RCC. Additionally, we have addressed the limitations on treatment of RCC in the region, capturing the restrictive situations of targeted therapy use in the Asia-Pacific region, mainly because of drug availability and treatment reimbursement. Often this illustrates the gap between Western and regional or even among local guidelines, the opinions of leading physicians regarding the treatment, and the realistic access to agents for most patients. Proposals made in this document are based on clinical experience and data from clinical trials of RCC therapies in which Asian patients have been included.