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H Akaza

Publications and source records attributed to H Akaza.

At least 91 records · Page 5Linked to original sources

Effects of soybean isoflavones on cell growth and apoptosis of the human prostatic cancer cell line LNCaP.

BACKGROUND: Epidemiological studies have suggested that soybean isoflavones are associated with a lower risk of prostate cancer. However, the mechanisms of prostate cancer prevention by soybean isoflavones have yet to be fully clarified. METHODS: Two soybean isoflavones (genistein and daidzein) and their glucosides (genistin and daidzin) were tested for their effects on cell growth and apoptosis of the LNCaP human prostatic cancer cell line. RESULTS: Among these isoflavones, genistein was found to inhibit the growth of LNCaP most effectively, with an IC50 value of 40 microM. The inhibition of cell growth by genistein was accompanied by the suppression of DNA synthesis and the induction of apoptosis. Expression of prostate-specific antigen (PSA) in LNCaP was also significantly reduced by the treatment with genistein. CONCLUSIONS: The results suggest that genistein might primarily influence human prostate cancer development by reducing tumor growth.

Apoptosis↗

Efficacy of dose-intensified MEC (methotrexate, epirubicin and cisplatin) chemotherapy for advanced urothelial carcinoma: a prospective randomized trial comparing MEC and M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin). Japanese Urothelial Cancer Research Group.

BACKGROUND: To evaluate the antitumor activity in patients with T3b, T4 or metastatic urothelial carcinoma treated with MEC or M-VAC chemotherapy, by performing a multi-center randomized prospective study. METHODS: From 1991 to 1995, 89 patients with T3b, T4 or metastatic urothelial carcinoma were randomly allocated to a methotrexate, epirubicin and cisplatin chemotherapy group (arm 1: S-MEC therapy; n = 29), a dose-intensified MEC therapy combined with G-CSF group (arm 2: I-MEC therapy; n = 30) or a methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy (arm 3: M-VAC therapy; n = 30). At the registration center, the patients were stratified into previously untreated patients and patients with recurrence after radical operation and then randomly allocated to the treatment groups. In each arm, two or more courses of chemotherapy (4-week cycles) were performed. RESULTS: Of the 88 eligible patients, four treated with S-MEC therapy and two treated with I-MEC therapy showed CR. The response rates (CR + PR) were 52% (15/29) with S-MEC therapy, 76% (22/29) with I-MEC therapy and 47% (14/30) with M-VAC therapy. The response rate with I-MEC therapy was significantly higher than that with M-VAC therapy (P = 0.02). Although the incidence of leukopenia was low with I-MEC therapy, the incidence of thrombocytopenia was high with this therapy. CONCLUSION: MEC therapy used in this study is promising in terms of the antitumor effects.

Adult↗

Serum creatinine level during chemotherapy for testicular cancer as a possible predictor of bleomycin-induced pulmonary toxicity.

BACKGROUND: Bleomycin is one of the key drugs used in induction chemotherapy for testicular cancer. Pulmonary toxicity is the major and potentially fatal adverse side-effect of this drug. METHODS: To evaluate the risk factors for bleomycin pulmonary toxicity, we retrospectively analyzed the cases of 20 men treated for metastatic testicular cancer at Tsukuba University Hospital between 1990 and 1996. All patients were treated with two to four cycles of a PVB regimen or BEP regimen. Recombinant human granulocyte colony-stimulating factor was used in all but one case. With a logistic procedure, we evaluated the age, total bleomycin dose, total cisplatin dose, renal injury, leukocytosis, smoking history, lung metastases and drug regimen as risk factors for a decrease in the diffusing capacity. RESULTS: Diffusing capacity was decreased to below 75% of the predicted values in nine patients. Elevation of the serum creatinine level was the most significant risk factor (P = 0.018) by the chi-squared test. A logistic regression analysis also indicated that the elevation of serum creatinine level was an independent risk factor for a decrease in the diffusing capacity (odds ratio 22.3, 95% Cl 1.02-487.3, P = 0.049). CONCLUSIONS: We recommend a pulmonary function assessment of patients receiving a relatively low dose of bleomycin, especially when an elevated serum creatinine level is seen during chemotherapy.

Antibiotics, Antineoplastic↗

Neutropenic colitis as a complication of high-dose chemotherapy for refractory testicular cancer.

A 44-year-old man received high-dose chemotherapy with carboplatin, etoposide and cyclophosphamide followed by autologous peripheral-blood stem-cell transplantation for treatment of refractory nonseminomatous testicular cancer (seminoma plus choriocarcinoma). The patient developed fever, watery diarrhea and abdominal pain at 10 days after the initiation of high-dose chemotherapy. Radiological examinations revealed adynamic ileus with thickened colon and small bowel wall and increasing ascites over the next 3 days. The patient subsequently suffered from disseminated intravascular coagulation, renal failure and hyperbilirubinemia despite systemic antibiotic therapy. Intensive medical care could barely avoid the fatal outcome. Neutropenic colitis has been recognized as a complication of acute leukemia or aplastic anemia. The present case indicates that this serious gastrointestinal complication can occur under profound neutropenic conditions induced by intensive chemotherapy for solid cancer.

Adult↗

High rate of induction of human autologous cytotoxic T lymphocytes against renal carcinoma cells cultured with an interleukin cocktail.

A high rate of induction (9 of 10 cases) of human autologous cytotoxic T lymphocytes (CTL) was achieved in vitro from peripheral blood mononuclear cells of renal carcinoma patients by applying an interleukin (IL)-cocktail consisting of IL-1, -2, -4, and -6. The CTL specifically lysed their own target carcinoma cells within 24 h but did not kill neighboring autologous normal kidney cells or allogeneic renal cancer cell lines. In the case of TUHR4TKB, for which autologous CTL were not induced, no expression of MHC class-I molecules was observed on the surface of these carcinoma cells, although they were sensitive to autologous natural killer cells. The results imply that adoptive immunotherapy for metastasized renal carcinoma will be feasible with autologous CTL in combination with natural killer cells.

Cell Survival↗

Bropirimine, an orally active anticancer agent for superficial bladder cancer.

OBJECTIVE: To investigate efficacy and safety of bropirimine, a new orally active interferon inducer, in patients with superficial bladder cancer. METHODS: Twenty patients with histologically confirmed recurrent superficial transitional cell carcinoma (Ta or T1) were studied. At least one marker lesion remained in all patients after transurethral resection. Bropirimine (750 mg) was given orally three times at 2-hour intervals (daily dose 2,250 mg) on 3 consecutive days weekly for 12 weeks. RESULTS: Of the 17 evaluable patients, 1 did not complete the treatment protocol. There were 5 responders, including 2 with a complete response (complete disappearance of the marker tumor) and 3 with a partial response (>50% reduction of the marker tumor). The objective response rate was 31.3% (5/16; 95% confidence interval 11.0-58.7%) for the 16 patients completing treatment and 29.4% (5/17; 95% confidence interval 10.3-56.0%) for the 17 evaluable patients. Adverse reactions occurred in 70.6% of the evaluable patients. Flu-like symptoms were most common, including malaise (23.5%), headache (23.5), and fever (11.8%), followed by gastrointestinal symptoms including less of appetite (23.5%). All of these reactions were tolerable. CONCLUSIONS: Bropirimine may be useful for the prophylaxis of recurrence following transurethral resection of superficial bladder cancer because it shows efficacy against marker tumors and has a good safety profile and oral activity.

Administration, Oral↗

Evaluation of nucleolar organizer regions in human bladder cancers by light- and electron-microscopic morphometry.

The number of nucleolar organizer regions (NOR) of human bladder cancers was evaluated at the light- and electron-microscopic level. The average number of argyrophilic NOR (AgNOR), stained by the one-step silver colloid method, was measured in benign and malignant urothelial cells in the human urinary bladder using a light microscope. The average number of nucleolar fibrillar centers (FC) per nucleus was also calculated by quantitative ultrastructural morphometry in the specimens from the same patients. Statistical evaluations revealed that the average number of AgNOR per nucleus was significantly correlated with the elevation of tumor grade and stage (p < 0.05). An average FC number per nucleus also increased in association with tumor grade and stage (p < 0.05). Although the average number of FC was 5.6 times higher than that of AgNOR, the correlation between the average number of FC and AgNOR was statistically significant. In conclusion, these results suggested that the silver staining method was a useful and convenient tool for the evaluation of the differentiation and invasive potential of bladder cancer cells at the light-microscopic level.

Biopsy, Needle↗

[A case of papillary cystadenoma of the epididymis].

We report a case of papillary cystadenoma of the right epididymis in a 48-year-old man. He consulted our hospital complaining of a small, painless mass at the upper pole of the right testis. There did not seem to be any remarkable problem of the mass. At 52 years old, the mass caused him pain, we diagnosed this case as chronic epididymitis, and performed right epididymectomy. On cut section, the tumor was multicystic and well encapsulated. The fluid within the cystic spaces was hemorrhagic. Microscopically, multimicrocysts were covered by tumor cells, which did not show any atypism or mitotic features. A papillary growth pattern was formed by vacuolated tumor cells around the capillaries in the microcysts, and a diagnosis of papillary cystadenoma of the epididymis was made. Papillary cystadenoma of the epididymis is considered a comparatively uncommon disease. To our knowledge, about 50 cases have been reported in the world literature, and this is the 17th case in Japan. Histologically, this tumor is similar in appearance to well-differentiated renal cell carcinoma, so it should be differentiated from metastatic renal cell carcinoma and multicystic papillary adenocarcinoma of the rete testis. The patient remains well with no evidence of recurrence or complication 8 months after excision. There is no evidence of renal cell carcinoma, nor features of von Hippel-Lindau's disease in this patient or his family.

Cystadenoma, Papillary↗

[Recurrent urological cancer--diagnose and treatment].

Clinical efforts to spare bladder function even in the case of muscle invasive recurrent bladder cancer is taking. Early detection of recurrence is essential for bladder sparing, and both urinary NMP22 and BTA are thought to have potency to detect recurrence of bladder cancer earlier than urinary cytology. Intravesical administration of BCG for superficial bladder cancer and intraarterial injection of chemoagents (Methotrexate and Cisplatin) with radiation for muscle invasive bladder cancer are thought to play important roles in sparing the bladder. Early detection of recurrent prostate cancer is becoming easier by ultrasensitive PSA assay. Though the value of early detection of recurrence is not proven since the benefits of early hormonal treatment have not yet been established, that should be a good indicator to evaluate new and coming treatments and play a important role to develop an effective treatment for recurrent prostate cancer.

Abdomen↗

[Effect of UFT on treatment of urological cancer--effect of UFT on treatment of invasive bladder cancer and advanced prostate cancer. Ibaraki Urological Cancer Chemotherapy Study Group].

A prospective randomized joint study was conducted to evaluate the usefulness of UFT 1) as a postoperative adjuvant therapy in patients with invasive bladder cancer who had undergone curative combination therapy with operation and/or chemotherapy and/or radiation therapy, 2) as an endocrine chemotherapy in patients with newly diagnosed stage C/D prostate cancer, for a period of 3 years from January, 1992. For bladder cancer, of 36 patients with invasive bladder cancer, clinically cured by combination therapy, 20 patients were treated with UFT as an adjuvant chemotherapy over 12 months, and they were compared to 16 patients with no adjuvant therapy. After excluding 10 inappropriate patients, 12 patients in the UFT treatment group and 14 patients with no adjuvant treatment group were observed. For prostate cancer, of 29 patients with clinically stage C/D prostate cancer, 13 were treated with endocrine therapy in combination with UFT, and 16 patients were treated with endocrine therapy alone. After excluding 7 inappropriate patients, 10 patients with endocrine chemotherapy and 12 patients with hormonal therapy were observed. The non-recurrence rate, survival rate and side effects of UFT were evaluated. In the study of bladder cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. In the study of prostate cancer, neither a significant difference of non-recurrent rate nor of survival rate was seen between the two groups. These findings suggest UFT is less useful as an adjuvant therapy for the invasive bladder cancer and as an endocrine chemotherapy for newly diagnosed advanced prostate cancer.

Administration, Oral↗

[Results of clinical study with epirubicin hydrochloride injectable solution for superficial bladder cancer. IMI28 Injectable Solution Study Group for Superficial Bladder Cancer].

A 7-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with superficial bladder carcinoma. Epirubicin-RTU at the dose of 60 mg/30 ml was administered by intravesical instillation once daily for three (3) consecutive days and a 4-day drug-free interval followed; then the above intravesical instillation of Epirubicin-RTU was repeated for three consecutive days. All 20 registered cases were eligible, and 18 cases completed the whole course of the study. In 18 completers, CR was observed in 12 cases and PR was observed in one (1) case, for an efficacy rate of 72.2%. The primary adverse reaction was bladder irritation including pollakiuria 85.0% (17/20), miction pain 85.0% (17/20), and hematuria 80.0% (16/20), which were all reversible and tolerable. In urinalysis, urinary sediment showed leukocytes and erythrocytes, and proteinuria was observed. All were reversible. From the above results, this new formulation of Epirubicin-RTU was considered useful for the treatment of superficial bladder carcinoma.

Administration, Intravesical↗

[Characteristics of screening-detected prostate cancer on health checkup].

Prostate cancer has the highest incidence and the second most common cause of death in U.S. men. In Japanese men, prostate cancer is not so common but is the most increasing neoplasm. Detection of early-stage cancer and early curative treatment are the most effective ways to reduce mortality from this disease. Therefore the mass screening system for prostate cancer to reduce mortality has become an important issue in recent years in Japan. The screening project for prostate cancer was conducted using only the prostate specific antigen (PSA) levels of primary screening with the cut off level of 4.0 ng/ml for candidates undergoing a medical checkup every 2 years. Totally, 20,338 men had health checkups every 2 years and 899 men requested the screening checkup for prostate cancer and their serum PSA level. Fifty (5.6%) men showed abnormal PSA level, 41 men had a second screening, 27 men underwent needle biopsy of prostate, and finally 14 cases of prostate cancer were detected. The detection rate calculated for prostate cancer was 1.56%. Thirteen cases out of 14 (92.9%) were clinically diagnosed as localized cancer. In 10 cases, total prostatectomy was performed and the pathological findings showed none of them to be clinically insignificant cancers. In conclusion, from our result the screening of prostate cancer using PSA only is considered to be very useful to detect early clinically significant prostate cancer.

Adult↗

[Percent free prostate-specific antigen: a marker for detection of prostate cancer].

We reviewed the use of percent free prostate specific antigen(PSA) to aid in the differentiation of benign and malignant prostate diseases. Percent free PSA may increase the sensitivity and specificity of PSA testing. There is evidence to suggest a benefit cost advantage to a tailored biopsy approach based on percent free PSA. However, differences in study designs and subject populations may account for the confusion in the current literature. Therefore, statistically valid multicenter clinical trials that take into account influencing factors are needed to set assay specific cut points and probability determinations.

Biomarkers, Tumor↗

[Recent advance in luteinizing hormone-releasing hormone analogue therapy in management of prostate cancer].

Luteinizing hormone-releasing hormone (LHRH) analogue therapy is one of the most widely used hormonal therapy for prostate cancer. LHRH analogue is effective and safety therapy for prostate cancer, when appropriate consideration is given to the disease flare. Recently, new long acting 3-month LHRH analogue depot has been developed and showed the therapeutic equivalence to the 1-month depot. In basic research, the expression of LHRH and its receptor has been demonstrated in some kinds of hormone depend cancer including prostate cancer. Although precise role of LHRH system in those cancers remains unclear, these findings suggests the presence of an autocrine system based on LHRH. More understanding of LHRH system might provide new treatment approaches to those cancer.

Antineoplastic Agents, Hormonal↗

Expression of cadherin-6 as a novel diagnostic tool to predict prognosis of patients with E-cadherin-absent renal cell carcinoma.

In many carcinomas, E-cadherin is considered to be a prognostic marker for patient survivals, and its decreased expression is associated with metastatic disease. Among renal cell carcinomas (RCCs), however, only 20% of tumors express E-cadherin, whereas a much higher percentage express other cadherins, e.g., N-cadherin and cadherin-6 (T. Shimazui et al, Cancer Res., 56: 3234-3237, 1996). Among these cadherins expressed in RCCs, cadherin-6 has been identified as a major cadherin in the renal proximal tubules and in the tumors themselves. Hence, we have investigated the relationship between prognosis and cadherin-6 expression in tumor cells in 43 patients with RCC. Expression of cadherin-6, E-cadherin, and alpha-catenin was detected immunohistochemically and evaluated microscopically as normal, heterogeneous, or absent. Normal, heterogeneous, and absent expression of cadherin-6 were observed in 19, 16, and 8 of 43 cases, respectively. Coexpression of E-cadherin and cadherin-6 was detected in only 10 cases. Among 30 tumors in which E-cadherin expression was absent, 24 expressed cadherin-6. In addition, the expression pattern of alpha-catenin correlated more highly with that of cadherin-6 than it did with E-cadherin (P = 0.0003 versus 0.025). In survival analyses, aberrant expression of cadherin-6 correlated with poor survivals both among all patients (P = 0.0009) and in those with E-cadherin-absent RCC (P = 0.0008). These results suggest that cadherin-6 is a major cadherin playing an essential role in cell-cell adhesion in E-cadherin-absent RCC.

Adolescent↗

[Clinical utility of the free prostate specific antigen (PSA), alpha 1-antichymotrypsin-complexed PSA, and free/total PSA ratio using the specific and sensitive enzyme-linked immunosorbent assay "E-plate EIKEN PSA"].

We studied the clinical significance of serum prostate specific antigen (PSA) ratio: free-PSA/total-PSA and free-PSA/complex-PSA to discriminate between prostate cancer (PC) and prostate benign disease (non-PCa) by using total-PSA, alpha 1-antichymotrypsin complexed (complex)-PSA and free-PSA enzyme-linked immunosorbent assay (ELISA) kits newly developed at EIKEN Chemical Co, Ltd. Fre-PSA and complex-PSA ELISA kits demonstrated high sensitivity and specificity. Total-PSA ELISA kit also demonstrated equimolarity for free-PSA and complex-PSA. On the total-PSA range of 4-10 ng/ml, free-PSA/total-PSA% (f/t%) and free-PSA/complex-PSA% (f/c%) were very useful to discriminate between PCa and non-PCa by receiver operating characteristic curve analysis as well as PSA density (PSA-D) but not free-PSA level. F/t% and f/c% were even useful to discriminate early stage PCa (i.e. A1 or B0) from non-PCa by the Mann-Whitney U-test.

Enzyme-Linked Immunosorbent Assay↗

Decreased expression of alpha-catenin is associated with poor prognosis of patients with localized renal cell carcinoma.

During the progression of many cancers, cell-cell adhesion molecules, e.g., E-cadherin (EC), may be down-regulated. In a number of carcinomas, EC has been described as an independent prognostic variable. We have studied the expression of adhesion molecules participating in cadherin-catenin complexes in renal cell carcinoma (RCC) specimens. Expression of EC, catenins and p120cas protein was examined in frozen tissue of 90 RCC specimens by immunohistochemistry, and these molecules were evaluated for their significance as prognostic markers. Staining was scored as normal (homogeneously positive at cell-cell borders) or abnormal (heterogeneous or absent). A significant correlation between poor survival and decreased expression of alpha-, beta- or gamma-catenin was observed, whereas no association between survival and EC or p120cas expression was seen. Cox's proportional hazard regression analysis showed that in patients with pT1-3N0M0 disease, reduced alpha-catenin expression correlated with poor survival, suggesting that alpha-catenin expression might be an independent prognostic indicator for patients of this group.

Adolescent↗

Protecting spermatogenesis from damage induced by doxorubicin using the luteinizing hormone-releasing hormone agonist leuprorelin: an image analysis study of a rat experimental model.

BACKGROUND: This study was performed to investigate the protective effect of a luteinizing hormone-releasing hormone (LHRH) agonist, leuprorelin, against spermatogenetic damage caused by doxorubicin in rats. METHODS: Sprague-Dawley rats were divided into 4 groups: (1) a control group, (2) a group given LHRH agonist (subcutaneous injections, total dose 9 mg/kg), (3) a group given doxorubicin (intraperitoneal injections, total dose 7.5 mg/kg), and (4) a group given both LHRH agonist (subcutaneous injections, total dose 9 mg/ kg) and doxorubicin (intraperitoneal injections, total dose 7.5 mg/kg). Evaluations were made by measuring body and testicular weights, determining Johnsen's score, and conducting DNA image analysis consisting of DNA content measurement (%1C, %2C, and %4C) by image cytometry. RESULTS: In the group given doxorubicin, the testicular weight was 1.47 +/- 0.24 mg, Johnsen's score was 4.4 +/- 1.2, and image analysis revealed %1C: 33.8 +/- 9.2, %2C: 43.9 +/- 16.3, and %4C: 5.0 +/- 4.4. In the group given both LHRH agonist and doxorubicin, the testicular weight was 1.32 + 0.23, Johnsen's score was 5.90 + 1.6, and image analysis revealed %1C: 46.9 +/- 15.0, %2C: 28.4 +/- 13.3, and %4C: 8.8 +/- 3.5. CONCLUSIONS: The significant prophylactic effect (P < 0.05) of the LHRH agonist against doxorubicin-induced spermatogenetic damage was demonstrated by Johnsen's score and image analysis (%1C, %2C, and %4C).

Animals↗