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Hideyuki Akaza

Publications and source records attributed to Hideyuki Akaza.

At least 55 records · Page 3Linked to original sources
PubMed2005

Lectin-reactive alpha-fetoprotein as a marker for testicular tumor activity.

BACKGROUND: Lens culinaris agglutin (LCA)-affinity electrophoresis resolves serum alpha-fetoprotein (AFP) into three isoforms, AFP-L1, -L2 and -L3. The ratio of AFP-L3 to total AFP (AFP-L3%) is frequently high in hepatocellular carcinoma (HCC) patients, and thus, it is widely used for early diagnosis of HCC. In the present study, we used the subfraction profile of LCA-binding AFP to diagnose and monitor testicular tumor activity. METHODS: Serum samples were collected from 21 testicular tumor patients, and the LCA-reactive fractions were determined by LCA-affinity electrophoresis coupled with antibody-affinity blotting. The histological diagnosis was non-seminomatous germ cell tumor (NSGCT) in 15 patients and pure seminoma in six patients. RESULTS: Serum AFP levels were abnormally elevated (>20 ng/mL) in 10 of 15 NSGCT patients. One NSGCT patient and two seminoma patients showed borderline AFP levels between 10 and 20 ng/mL. LCA-reactive AFP was detected in all 11 NSGCT patients with serum AFP levels above 10 ng/mL, but not in the two seminoma patients with serum AFP levels above 10 ng/mL. In testicular tumor patients, the broad band of AFP-L2 could not be completely separated from AFP-L3. The mean ratio of AFP-L3 plus AFP-L2 (AFP-L2 + 3%) was as high as 94% (range 80-99%) in these patients. Serial determinations of LCA-reactive fractions were performed in eight of the 11 LCA-reactive AFP-positive patients. They included five patients who received chemotherapy, and three patients who underwent orchiectomy for stage I NSGCT. In three of eight patients, LCA-reactive AFP was detected even after normalization of total AFP levels. All three patients relapsed, with elevation of serum AFP within several months. CONCLUSION: Determination of LCA-reactive AFP might be a useful marker for testicular tumor activity in patients with lower AFP levels.

Adult↗
PubMed2005

Serum creatinine and cholesterol levels of testicular cancer patients in long-term follow up.

PURPOSE: Most patients with advanced testicular cancer can be cured with cisplatin-based chemotherapy. Therefore, the long-term effects of the treatment are clinically important. In the present study, we evaluated the serum creatinine and cholesterol levels of long-term survivors of testicular cancer. METHODS: Serum creatinine and cholesterol levels were determined in 23 testicular cancer patients who had received cisplatin-based chemotherapy more than 5 years earlier. They were compared with a control group of 16 patients who did not receive chemotherapy. In addition, follow-up data of beyond 10 years after the initial treatment was obtained from 17 patients. We also analysed the trends of both serum creatinine and cholesterol determinations over 10 or more years using a generalized linear model. RESULTS: There was no significant difference in the serum creatinine and cholesterol levels 5 years after the treatment between the chemotherapy and control groups. Analysis using a generalized linear model showed a significant trend toward an increase in serum creatinine in patients who had developed renal dysfunction during chemotherapy (P = 0.0024). The elevation of the serum creatinine level was mainly observed during the first 5 years. In addition, a significant trend toward an increase in serum cholesterol was revealed in both the chemotherapy and control groups. CONCLUSION: Patients who have developed renal dysfunction during chemotherapy may be at risk of gradually increasing serum creatinine levels even after it has become normal. Although further analysis is needed, we recommend long-term follow up in the survivors of metastatic testicular cancer patients treated with cisplatin-based chemotherapy.

Adult↗
PubMed2005

Retroperitoneal extragonadal germ cell tumor in a patient with Klinefelter's syndrome.

A 22-year-old man was diagnosed with retroperitoneal seminoma associated with Klinefelter's syndrome. The tumor was 14 x 12 cm in size and surrounded the superior mesenteric artery. He received induction chemotherapy with bleomycin, etoposide and cisplatin (BEP) followed by salvage chemotherapy with paclitaxel, ifosfamide and cisplatin (TIP). The tumor considerably decreased in size and remains as a poorly defined plaque. At the time of writing, he is being followed closely and is free from progression.

Adult↗
PubMed2005

Acute multifocal bacterial nephritis complicated with acute renal failure and thrombocytopenia.

A 50-year-old woman was transferred to our hospital because of acute renal failure and thrombocytopenia. Due to rapid enlargement of the kidney, we first suspected that she had diffuse renal invasion of anaplastic carcinoma or lymphoma of the kidney. Anti-bacterial treatment for complicated urinary tract infection and hemodialysis treatment resulted in recovery of both renal function and thrombocytopenia. Serial CT study demonstrated disappearance of kidney swelling and multiple masses within the kidney. We finally made a diagnosis of acute multifocal bacterial nephritis. Timely initiation of dialysis therapy and appropriate anti-bacterial treatment was essential to rescue this case.

Acute Disease↗
PubMed2005

Gene expression profiles correlate with the morphology and metastasis characteristics of renal cell carcinoma cells.

Renal cell carcinoma (RCC) shows various clinical behaviors, and currently surgical modalities are the only effective therapy against this cancer. To discern the genomic background affecting clinical characteristics such as metastasis, we analyzed the gene expression profiles of the RCCs by DNA microarray using cell lines originating from primary or metastatic lesions. RNA was extracted from ten SKRC RCC cell lines and gene expression profiling was performed using a cDNA microarray of nearly 4,000 human cDNA clones. We compared the gene expression profiles between these SKRC cell lines and the normal renal proximal tubular cell line and among SKRC cell lines that showed different characteristics. The clustering of the selected 62 genes revealed similar profiling patterns between SKRC-17 and SKRC-29 cells that were derived from metastatic RCC lesions. Another cell line from a metastatic lesion, SKRC-52, with a unique spindle-shaped morphology, had a different pattern of expression profiling from the other cell lines. We found several genes up-regulated in the cell lines from metastatic lesions; transgelin, which is reportedly involved in cell proliferation and migration, was up-regulated in SKRC-52. The unique profiling pattern of gene expression clearly correlated with cell morphology and metastatic potential. Such profiling might contribute to identifying the genes involved in the clinical characteristics of RCC.

Carcinoma, Renal Cell↗
PubMed2005

[Cancer screening].

The purpose of cancer screening is to widen the difference between morbidity and mortality of the target cancer. Since 1983 cancer screening has been supported by the Japanese government. Initially it covered gastric and cervical cancer with lung, breast and endometrial cancers supported from 1987 and colorectal cancer in 1992. Since 1998 support for cancer screening has been transferred to local government. It is generally accepted that the uptake of screening services is too low. Estimates for Japan suggest that at best 30% of the eligible population accept the services. In other parts of the world screening is more widely accepted, for example, 67% for breast cancer and 79% for cervical screening in the USA. Barriers within Japan for increasing screening are complex and include, legal, ethical, financial, technical infrastructure, data related matters and the level of understanding and education of the general public. In 2000 the MHLW conducted an evaluation of cancer screening in terms of usefulness and effectiveness. It concluded that fair or better evidence for reduction in mortality existed for cervical cancer (cytology), breast cancer (mammography with clinical examination for women aged > or = 50 years), colorectal cancer (faecal occult blood test), gastric cancer, lung cancer and liver cancer. As a step towards improving screening services and their uptake by the general public a new Research Centre for Cancer Prevention and Screening was established at the National Cancer Centre in October 2003. This and other initiatives will build on the progress of the past 20 years but it is generally agreed that there is still have a long way to go.

Adult↗
PubMed2005

[Recent advancement in diagnosis and treatment of prostate cancer--general concepts].

Prostate cancers which are diagnosed during PSA screening include a significant number of clinically insignificant cancers. Useful strategy for needle biopsy is warranted. In addition, useful strategy for the timing of radical therapy for localized prostate cancer is warranted to be established. These strategies are essential to avoid over-diagnosis and over-treatment.

Androgen Receptor Antagonists↗
PubMed2005

Effectiveness of Maximal Androgen Blockade (MAB): illusion or reality?

Two decades have passed since the concept of Maximal Androgen Blockade (MAB) was first applied to the clinical treatment of prostate cancer. The theory is that by cutting off the supply of androgen from the adrenal gland, androgen blockade of the prostate could be made more complete. However, to date the clinical benefit of MAB has failed to live up to the theoretically expected effect. Having said that, fundamental research and clinical trials in recent years do indicate that the benefit of MAB is not merely an illusion.

Aged↗
PubMed2005

[Cancer prevention].

The 12 th Oncology Forum discussed the progress and future strategy of cancer prevention in Japan. The National Cancer Center has established a research center for screening focusing on the most common six cancer, stomach, lung, liver, colon, breast and uterus cancer. The program so far had a cumulative detection rate of 3.3%, which is high,and may reflect the selection of subjects. Screening and chemoprevention is also being investigated in prostate cancer, but the issues centre on how to make this widely available. High risk subjects can also be identified for breast cancer. Obesity and family history are especially important. In colorectal cancer studies are evaluating different diets, but general application is not yet possible and the infrastructure to implement any general screening and prevention does not exist. Development of pharmaceutical treatments for prevention is difficult because of the need for very safe treatments, and also because of the length of time needed to carry out studies. Overall, cancer prevention is still in evolution. New approaches are needed, and new infrastructure will be needed at a government level to implement this.

Breast Neoplasms↗
PubMed2005

[Usefulness and positioning of MAB therapy for prostate cancer].

Prostate cancer is a relatively slow-growing disease compared to other cancers, and the patients tend to be older. Taking into consideration therefore life expectancy of the patients and risks of recurrence and progression, conservative treatments (mainly hormonal therapy) are often applied for early cases, as well as radical treatments (total prostatectomy and radiotherapy). Particularly in Japan, many patients start treatment with hormonal therapy alone, in both early and advanced cases. Hence, Maximal Androgen Blockade (MAB) therapy, in which surgical or medical castration (such as LH-RH agonist treatment) and anti-androgen treatment are combined, is widely exercised with the hope to enhance treatment effects. The usefulness of MAB therapy has been assessed in a number of randomized comparative studies, covering mainly metastatic cases. The efficacy of the therapy with the use of flutamide as non-steroidal anti-androgen has been confirmed in some of the studies, although the magnitude of the efficacy cannot be said major. In Phase III clinical studies of MAB therapy with bicalutamide being conducted in Japan for patients in Stages C and D, however, the patient group treated with MAB therapy demonstrated more favorable results compared to the group treated with LH-RH agonist alone, particularly in terms of time to progression (TTP) of the patients in Stage C. These are relatively new findings on the usefulness and adaptability of MAB therapy. In this Panel Discussion, views and experiences are exchanged on a wide variety of topics covering the real usefulness of MAB therapy, its adaptability, possible outcomes of hormonal therapy in early cases, and the future of MAB therapy, taking into account the prevailing opinions and current practices on prostate cancer in both the United States and Japan.

Androgen Antagonists↗
PubMed2004

HPC2/ELAC2 polymorphism associated with Japanese sporadic prostate cancer.

BACKGROUND: HPC2/ELAC2 gene was identified by linkage analysis from familial prostate cancer (Pca) patients in USA. To determine the association of HPC2/ELAC2 gene with Japanese sporadic Pca, we performed a case-control study focused on two missense polymorphisms. METHODS: We genotyped the two polymorphic sites of Ser217Leu and Ala541Thr in sporadic Japanese Pca patients (n = 285) and matched controls (n = 233). Controls were unrelated Japanese outpatients who had no history of any cancer and normal PSA level (less than 4.0 ng/ml). Statistical analyses were performed by Mann-Whitney's U-test, Fisher's exact test, and logistic regression analysis. RESULTS: We observed a significantly higher frequency of the Thr allele at 541 polymorphic site in Pca patients (8.4%) compared to the control group (2.1%) (P = 0.0030, Odds Ratio (OR) = 4.02, 95% CI = 1.50-10.8). However, this SNP does not correlate with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. No association was identified at Ser217Leu polymorphic site. CONCLUSIONS: Our results indicate that Thr allele at 541 in HPC2/ELAC2 has strong significance in the predisposition of sporadic Pca in Japan. This polymorphism can be useful to predict the personal Pca risk, which lead the effective screening of Pca.

Aged↗
PubMed2004

Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis.

The induction of phase 2 detoxifying enzymes, such as UDP-glucuronosyltransferases (UGTs), in response to an array of naturally occurring and synthetic agents, such as oltipraz (4-methyl-5-[2-pyrazinyl]-1,2-dithiole-3-thione), provides an effective means of protection against a variety of carcinogens. Transcription factor Nrf2 is an essential regulator of the inducible expression of detoxifying enzyme genes by chemopreventive agents. In this study, we investigated in Nrf2-deficient mice the susceptibility to the urinary bladder-specific carcinogen N-nitrosobutyl(4-hydroxybutyl)amine (BBN) and the chemopreventive efficacy of oltipraz. The incidence of urinary bladder carcinoma by BBN was significantly higher in Nrf2-/- mice than in wild-type mice; invasive carcinoma was found in 24.0 and 38.5% of wild-type and Nrf2-/- mice, respectively. Oltipraz induced the phase 2 enzymes responsible for BBN detoxification in the liver and urinary bladder in an Nrf2-dependent manner. As expected, therefore, oltipraz decreased the incidence of urinary bladder carcinoma by BBN in wild-type mice but had little effect in Nrf2-/- mice. In wild-type mouse liver, oltipraz significantly induced BBN glucuronidation and decreased the urinary concentration of N-nitrosobutyl(3-carboxypropyl)amine, a proximate carcinogen of BBN. Importantly, BBN was found to suppress the expression of UGT1A specifically in the urinary bladder. This suppression was counteracted by oltipraz in wild-type mice but not in Nrf2-/- mice. These results show that Nrf2 and its downstream target genes are responsible for BBN detoxification. Furthermore, oltipraz prevents carcinogenesis by BBN by enhancing detoxification of this carcinogen in the liver and urinary bladder.

Animals↗
PubMed2004

The level of cadherin-6 mRNA in peripheral blood is associated with the site of metastasis and with the subsequent occurrence of metastases in renal cell carcinoma.

BACKGROUND: To evaluate the significance of the presence of circulating renal cell carcinoma (RCC) cells in the development of metastases, the authors extended a previous study to quantify cadherin-6 mRNA levels in association with the pattern of metastasis. METHODS: Cadherin-6 mRNA levels were measured in peripheral blood samples from 66 patients with RCC, including 55 patients who had newly diagnosed RCC (43 without metastases and 12 with metastases) and 11 patients who had recurrent RCC. For quantitative polymerase chain reaction analysis, a cutoff value was determined in blood samples from 25 healthy volunteers and was verified in samples from 5 healthy controls and from 10 patients who had other malignancies. The correlation between the site of metastases and the cadherin-6 mRNA level was analyzed, and a follow-up study (median, 39 months) to track subsequent metastases was performed after patients underwent nephrectomy. RESULTS: Cadherin-6 was found in 69.9% of patients with metastases and in 34.9% of patients without apparent metastases (P = 0.0099). In the group of patients with recurrent RCC, patients who had only pulmonary metastases had a significantly lower positivity rate (25.0%) compared with patients who had distant metastases (85.7%; P = 0.044). Among 43 patients with newly diagnosed RCC, 5 of 15 patients who were positive for cadherin-6 had metastases after nephrectomy, whereas only 2 of the 28 patients with negative cadherin-6 status had recurrent disease (P = 0.0398). In addition, the recurrence-free survival of patients who were positive for cadherin-6 was poorer compared with the survival of patients who were negative for cadherin-6 (P = 0.062). CONCLUSIONS: The quantification of cadherin-6 mRNA in peripheral blood may be a significant predictive marker for current and future metastases. However, subsequent metastases did not always correlate with levels of cadherin-6 mRNA. This may have been due either to the small numbers of circulating tumor cells or to the low levels cadherin-6 mRNA in circulating tumor cells.

Biomarkers, Tumor↗
PubMed2004

Phase I/II clinical trials of carbon ion therapy for prostate cancer.

BACKGROUND: Heavy ion beams possess high linear energy transfer components and a prominent Bragg peak in the human body, resulting in higher relative biological effectiveness and improved dose distribution. To establish heavy ion therapy techniques for the treatment of prostate cancer, phase I/II clinical trials were initiated. METHODS: For 96 patients with T1b-T3 prostate cancer, three carbon ion beams were used to irradiate the prostate and seminal vesicles (20 times/5 weeks) with or without endocrine therapy. Radiation dose was expressed in GyE which was initially thought to be equivalent to photon dose. Total dose was gradually increased from 54 to 72 GyE. RESULTS: Carbon ion therapy was completed in 20 cases of T1b/T1c/T2aN0M0 as monotherapy, in 8 cases of T2b/T3pN0M0 with neoadjuvant endocrine therapy, and in 68 cases of T2b/T3N0/pN1M0 with neoadjuvant and adjuvant endocrine therapy. Median observation period was 47 months. Grade 3 late radiation morbidity of rectum and/or bladder/urethra developed in one and five cases who received 66 and 72 GyE of radiation, respectively. After these adverse effects were observed, total dose was decreased to 66 GyE and the radiation field was coned down during the treatment course. At 5 years, overall, cause-specific, clinical recurrence-free, and biochemical recurrence-free survival rates were 87.7, 94.9, 90.0, and 82.6%, respectively. Local control was achieved in all patients except one patient who received 54 GyE of radiation. CONCLUSIONS: The therapeutic techniques of carbon ion therapy have been established for patients with prostate cancer. Carbon ion therapy may exert excellent effect to the tissues of prostate cancer.

Carbon↗
PubMed2004

Reiter's syndrome following intravesical bacille biliE de Calmette-GuErin treatment for superficial bladder carcinoma: report of six cases.

We report the cases of six patients who developed acute Reiter's syndrome following intravesical bacille biliE de Calmette-GuErin (BCG) immunotherapy for superficial bladder cancer. After the third to eighth BCG intravesical injection, the patients developed conjunctivitis, aseptic urethritis, and polyarthritis consistent with a diagnosis of Reiter's syndrome. HLA-B27 antigen was negative in five of the patients examined. Two of the patients responded to nonsteroidal anti-inflammatory drugs for polyarthritis, and the other four responded to steroids (prednisolone 5-10 mg/day). The frequent use of intracavitary BCG may increase the incidence of BCG-induced Reiter's syndrome. Further analysis of the relationship between HLA-B and -DR alleles and arthritis should shed light on the mechanism of BCG-induced Reiter's syndrome.

Journal Article↗
PubMed2004

Effect of prophylactic treatment with intravesical epirubicin on recurrence of superficial bladder cancer--The 6th Trial of the Japanese Urological Cancer Research Group (JUCRG): a randomized trial of intravesical epirubicin at dose of 20mg/40ml, 30mg/40ml, 40mg/40ml.

OBJECTIVES: We compared the prophylactic efficacy and safety of epirubicin (EPI) in primary superficial bladder cancer. METHODS: The major inclusion criteria were primary superficial bladder tumour (Ta, T1, G1, G2) and new cases of primary multiple tumours, or recurrent cases. The major exclusion criteria were Tis or G3 tumours. Group A received 17 doses of EPI 20mg/40ml over a period of 12 months for a total dose of 340mg. In contrast, Group B received 12 doses of EPI 30mg/40ml over a period of 7 months, while Group C received 9 doses of EPI 40mg/40ml over a period of 4 months, both for a total dose of 360mg. This study enrolled a total of 622 patients diagnosed as having primary superficial bladder cancer during the period from June 1994 through November 1996 at the 118 institutions. Follow-up of the patients was conducted through October 1999. RESULTS: The relationship between the EPI concentration and the recurrence-free rate was evaluated by Tarone's test, and it was found that the recurrence-free rate became significantly higher as the drug concentration increased (p=0.0375). In the safety evaluation, with regard to adverse drug reactions, pollakiuria and pain on urination occurred at significantly higher incidences as the concentration of the EPI solution increased. CONCLUSIONS: The greatest effect of intravesical instillation of EPI after TUR-BT was shown by the regimen using the highest concentration of the drug solution which was administered during a short period of time.

Administration, Intravesical↗
PubMed2004

Phase I study of autologous tumor vaccines transduced with the GM-CSF gene in four patients with stage IV renal cell cancer in Japan: clinical and immunological findings.

We produced lethally irradiated retrovirally GM-CSF-transduced autologous renal tumor cell vaccines (GVAX) from six Japanese patients with stage IV renal cell cancer (RCC). Four patients received GVAX ranging from 1.4 x 10(8) to 3.7 x 10(8) cells on 6-17 occasions. Throughout a total of 48 vaccinations, there were no severe adverse events. After vaccination, DTH skin tests became positive to autologous RCC (auto-RCC) in all patients. The vaccination sites showed significant infiltration by CD4(+) T cells, eosinophils, and HLA-DR-positive cells. The kinetic analyses of cellular immune responses using peripheral blood lymphocytes revealed an enhanced proliferative response against auto-RCC in four patients, and cytotoxicity against auto-RCC was augmented in three patients. T cell receptor beta-chain analysis revealed oligoclonal expansion of T cells in the peripheral blood, skin biopsy specimens from DTH sites, and tumors. Western blot analysis demonstrated the induction of a humoral immune response against auto-RCC. Two of the four patients are currently alive 58 and 40 months after the initial vaccination with low-dose interleukin-2. Our results suggest that GVAX substantially enhanced the antitumor cellular and humoral immune responses, which might have contributed to the relatively long survival times of our patients in the present study.

Aged↗