Search

Objective: Genetic factors are thought to be one of the causes of individual variability in the adverse reactions observed in cancer patients who received gemcitabine therapy. However, genetic factors determining the risk of adverse reactions of gemcitabine are not fully understood., Patients and Methods: To identify a genetic factor(s) determining the risk of gemcitabine-induced leukopenia/neutropenia, we conducted a genome-wide association study, by genotyping over 610 000 single nucleotide polymorphisms (SNPs), and a replication study in a total of 174 patients, including 54 patients with at least grade 3 leukopenia/neutropenia and 120 patients without any toxicities., Results: We identified four loci possibly associated with gemcitabine-induced leukopenia/neutropenia [rs11141915 in DAPK1 on chromosome 9q21, combined P=1.27×10, odds ratio (OR)=4.10; rs1901440 on chromosome 2q12, combined P=3.11×10, OR=34.00; rs12046844 in PDE4B on chromosome 1p31, combined P=4.56×10, OR=4.13; rs11719165 on chromosome 3q29, combined P=5.98×10, OR=2.60]. When we examined the combined effects of these four SNPs, by classifying patients into four groups on the basis of the total number of risk genotypes of these four SNPs, significantly higher risks of gemcitabine-induced leukopenia/neutropenia were observed in the patients having two and three risk genotypes (P=6.25×10, OR=11.97 and P=4.13×10, OR=50.00, respectively) relative to patients with zero or one risk genotype., Conclusion: We identified four novel SNPs associated with gemcitabine-induced severe leukopenia/neutropenia. These SNPs might be applicable in predicting the risk of hematological toxicity in patients receiving gemcitabine therapy.

A 70% EtOH extract from the bark of Syringareticulata has shown significant antioxidant activity. Chemical study on the extract resulted in the isolation of seventeen compounds (1-17), including a novel oleoside-type secoiridoid glucoside, reticuloside (1), and the structures were elucidated on the basis of extensive spectroscopic analyses. Among the isolated compounds, jaspolyoside (2), oleuropein (4) and 2-(3,4-dihydroxy)-phenylethyl-β-d-glucopyranoside (17), showed the most potent superoxide anion scavenging activity with the EC(50) values of 4.97, 2.57 and 4.97μM, respectively. The structure-activity relationship indicated that the presence of 2-(3,4-dihydroxyphenyl)-ethoxy group is important for exhibiting the activity., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Hyperacute humoral rejection of ABO-incompatible kidney transplants limits the application of this procedure. We evaluated the effect of 4-week treatment with mycophenolate mofetil (MMF), a compound that inhibits antibody production by B cells, before ABO-incompatible living-donor kidney transplantation with tacrolimus as the primary immunosuppressant. In contrast with cases without MMF pretreatment, we did not observe any graft loss caused by hyperacute humoral rejection in the 18 patients who received MMF. Overall, the incidence of adverse events was comparable in the MMF-treated and -untreated groups. The administration of MMF 4 weeks before kidney transplant effectively inhibits B-cell function, suggesting a potential role for MMF in the prevention of humoral rejection.

Three cases of bladder stones at the ureterovesical anastomotic site after renal transplantation (RT) are reported. The three patients were successfully treated with kidney grafts. The method used for the ureter bladder anastomosis in all patients was the extravesical technique with polyglyconate (Maxon) for case 1 and a polydioxanone suture (PDSII) for cases 2 and 3. Calculi formation was found between 3 to 15 months after RT. Endoscopic vesicolithotripsy was performed and the stones adherent to the ureterovesical anastomotic site were removed successfully in all cases. Stone analysis revealed uric acid (case 1), CaOx and CaP (case 2). Stone analysis was not done in case 3. The patients' symptoms improved and no bladder stones could be discerned postoperatively.

A 43-year-old man visited our clinic with gross hematuria. Ultrasonography and computed tomography demonstrated a tumor at the bladder dome. Cold punch biopsy revealed well-differentiated adenocarcinoma and stage III A urachal carcinoma was diagnosed. Neoadjuvant intra-arterial chemotherapy with cisplatin, adriamycin and angiotensin II was performed and 40% reduction of tumor size was noted 3 weeks after this therapy. En bloc segmental resection was performed. Augmentation ilealcystoplasty was subsequently performed to secure bladder capacity. Adjuvant chemotherapy (UFT) was given for 1 year. Cystolithotomy and closure of ventral hernia were required 10 years after radical surgery for postoperative complications. The patient has survived 12 years with no evidence of local recurrence or distant metastasis.

We describe 4 cases of bilateral synchronous renal cell carcinoma and 3 of renal tumor in solitary kidney. One of the 3 patients with renal tumor in solitary kidney underwent partial nephrectomy. The remaining 2 patients, who had renal tumors greater than 7 cm located in the central region, underwent extracorporeal surgery. Development of acute renal failure and renal bleeding after ex vivo surgery occurred in 1 female patient, who required autograftectomy and temporary dialysis but subsequently underwent a re-operative procedure for renal transplantation with a kidney donated by her 82-year-old mother. Two of the 4 patients underwent partial nephrectomy, 1 with multiple bone and lung metastases had all carcinoma foci extracted at the second stage and was administered UFT and IFN alpha, and the remaining 2 patients, who both had hereditary renal cell carcinoma with multiple tumors in both kidneys, received living-donor related renal transplantation soon after bilateral nephrectomy. In the period of follow-up, ranging from 2 to 14 years, all the patients are well with no relapse and have good renal function. These results indicate kidney transplant procedures may have been linked with the options of bilateral synchronous renal cell carcinoma and renal tumor in solitary kidney.

Ten patients with hormone relapsing metastatic prostate cancer who had been previously treated with extensive radiotherapy for metastasis and chemotherapy including docetaxel and platinum compounds were evaluated to determine the safety and efficacy of docetaxel with high-dose calcitriol and platinum compound combination intra-arterial chemotherapy. Nine patients with ECOG performance status 3 or greater, and 9 with 12-month survival probability less than 0.5 in the CALGB prognostic model, including 3 aged over 80, were assessable for therapeutic results, adverse events and clinical benefit response. Improvement of QOL and relief of the bone pain were seen immediately after the intra-arterial chemotherapy treatment. Considering that high-dose calcitriol and platinum compound combination intra-arterial chemotherapy is easily administered without major toxic events even to outpatients, it will be a treatment option for the clinical benefit of relapsing prostate cancer patients with poor prognoses.

The patient was a 63-year-old woman who had been diagnosed with advanced bladder cancer with renal dysfunction and bilateral bulky pulmonary metastasis. Initially, the primary lesion was resected and the implantation of an infusion catheter and port system was performed. Following surgery, she received intermittent intra-arterial (IA) low-dose CDDP chemotherapy via the infusion port and concurrent bronchial arterial infusion and radiation (40 Gy for the left lung). About 3 months later, the right and left lung metastases were reduced 63% and 91%, respectively, and a right lower lobectomy was performed. CDDP was administered through the outpatient clinic ever since. From January 2001, we began to use docetaxel (TXT) for CDDP because of continuous grade 2 nausea and appetite loss. There were no adverse effects by TXT. Repeated IA chemotherapy was discontinued from June 2001 because of neurological symptoms. In September 2001, a left skull base metastasis was detected and was treated by radiation 40 Gy. In November 2002, a left patella metastasis appeared and was treated by IA chemotherapy with angiotensin II and radiation 30 Gy. We confirmed that multidisciplinary treatment contributed to her approximately 3-year survival with good QOL. The cancers in both lungs could be kept under control until her death.

Between 1986 and 1995, 218 patients with primary carcinoma of the bladder were treated with radical cystectomy at our hospitals. Clinicopathological specimens and the relative value of prognostic factors were analyzed with both the univariate and multivariate method. Univariate analysis indicated that age, sex, pathological tumor stage, grade, vessel involvement, tumor infiltrating type and positive nodes were predictive of poor cancer-specific survival. Multivariate analysis demonstrated that female patients were predictive of poor cancer-specific survival. As for the risk ratio, the prognostic factors in lymphatics involvement and tumor infiltrating type were 2.77 and 2.47, respectively.

Background: Renal artery aneurysms (RAAs), once considered rare, are being recognized with increasing frequency. The treatment of aneurysms of the first ramification of the main renal artery is still controversial., Methods: From November 1984 to May 1992, we treated 8 patients with RAA at the first ramification. All the patients were treated with an ex vivo technique and autotransplantation., Results: The results, evaluated with intravenous pyelogram and arteriography were satisfactory. No operative deaths and no complications were noted., Conclusion: We concluded that surgery with an ex vivo technique and autotransplantation is an excellent method of treating this type of lesion.

Computer processed adrenal imaging using dual-radioisotopes, 6 beta-iodomethyl-19-nor-cholest-5(10)-en-3 beta-ol-131I and 99mTc-phytate was performed in 12 patients with primary aldosteronism and 4 with Cushing's syndrome due to adrenocortical tumor. Adreno-photoscanning and hepato-photoscanning were performed in the same position 2-4 days following intravenous administration of radiocholesterol. The scintigraphic information was stored on cassettes and scan subtraction and a digital-computer method for data smoothing were performed on an oscilloscope. The tumor site could be determined in all cases until day 4 by this computer processed image.

Intracarotid CDDP infusion in combination with angiotensin II was performed in two patients with metastatic brain tumor, lung carcinoma (LC) and ovarian carcinoma (OC). The patient with OC received 40 mg/m2 CDDP while the other patient with LC was administered intra-arterially with 50 mg/m2 CDDP, 30 mg/m2 ADM and 2.5 mg/m2 MMC. 50% or greater reduction in the size of metastatic lesions was observed in both patients in whom no neurological toxicities developed. Intra-arterial infusion of CDDP either alone or in combination with ADM or MMC seems to present an aggressive approach in dealing with other metastatic neoplasms without increasing toxicity, especially if intra-arterial angiotensin II is infused concomitantly.

Endogenous androgen levels of prostatic tissues in patients with benign prostatic hypertrophy (BPH) and untreated prostatic cancer (PC) were determined by radioimmunoassay using sephadex LH-20 column chromatography. By this assay procedure, it was possible to measure tissue androgen levels with only 30 approximately 40 mg weight of tissues. In BPH (n=20) the concentrations of steroids (mean +/- standard deviation, ng/g. tissue weight) were 5 alpha-androstane 3 alpha, 17 beta diol (A-diol), 2.31 +/- 1.29; dihydrotestosterone (DHT), 4.97 +/- 2.17; testosterone (T), 0.62 +/- 0.33. In PC (n=17) the concentrations were 5.51 +/- 3.23; 3.94 +/- 3.16; and 0.93 +/- 0.38; respectively. The concentrations of DHT were raised and the levels of A-diol were reduced significantly (P less than 0.01) in BPH compared with PC. Tissue DHT levels of PC were variable, but they could be classified in to two groups. One was below 2 ng levels (n=8) similar to those of non-androgen target tissues and the other was over 2 ng (n=19). The relationships between histological differentiation and tissue DHT levels in prostatic cancer were examined. In poorly differentiated cancer (n=4), DHT levels were low in all cases, furthermore even in well differentiated ones there were 4 cases with levels below 2 ng. Thus, the measurement of endogenous DHT levels of prostatic tissues was considered to be valuable for the judgment of androgen dependency in prostatic cancer.

R 1881 binding receptor and DHT concentrations in human prostatic cytosol were assayed in surgically removed prostatic tissues of benign prostatic hyperplasia (BPH) and of the normal prostate. The normal prostates were obtained from totally cystectomized male patients with bladder cancer. Cytosols were incubated with 0.25--8.0 nM (6 points) of 3H-R 1881 in the presence or absence of excess radioinert R 1881 at 4 degrees C for 20 hours, thereafter treated with 0.5% dextran coated charcoal. Specific bindings were analysed in the form of scatchard plot analysis. Cytosol DHT levels were determined by radioimmunoassay reported previously. Steroid specificity studies revealed that R 1881 binding receptor was inhibited not only by androgens but also by progesterone, however, an addition of 1000 fold excess triamcinolone acetonide (TCA) reduced the inhibition by progesterone. As R 1881-receptor complex was eluted at the void volume of sephacryl S-200 chromatography, the receptor was considered to be 8-9S protein. Cytosol DHT levels were 35.5 +/- 13.6 pg/mg cytosol protein in BPH and 18.9 +/- 7.1 pg/mg protein in the normal prostates, showing a significantly higher value in the former (p less than 0.01). Kd and NBS of R 1881 receptor in BPH were 0.73 +/- 0.21 nM and 30.1 +/- 9.0 fmol/mg cytosol protein and those in normal prostate were 0.68 +/- 0.28 nM, 10.2 +/- 4.2 fmol/mg protein, respectively. NBS were also higher in BPH compared to the normal prostate (p less than 0.001). Moreover, DHT levels (y) and NBS (x) showed a significant correlation (y = 0.631 X + 15.764, r = 0.506).(ABSTRACT TRUNCATED AT 250 WORDS)

A combination of 50 to 80 mg. per m.2 cis-platinum and 30 to 50 mg. per m.2 doxorubicin or 30 to 50 mg. per m.2 tetrahydropyranyl-doxorubicin instead of doxorubicin was infused into the bilateral internal iliac artery for the treatment of 20 patients with T3 or T4 advanced bladder cancer. Angiotensin II was administered together with these chemotherapeutic agents by means of an infusion pump at a rate of 1.5 to 2.0 micrograms. per minute for 20 minutes for both sides. Among the 20 patients complete (9) and partial (8) responses were obtained after only 1 or 2 courses of this intra-arterial treatment. Histological examination showed severe tumor destruction with no viable cells in 6 and no tumor in 4 of the 15 evaluable cases. Selective enhancement of regional blood flow in the tumor region after intra-arterial infusion of angiotensin II was observed by continuous target arterial 81mkrypton infusion. Intra-arterial chemotherapy with combined angiotensin II may be clinically useful for treatment of primary or metastatic bladder carcinoma.

A radioimmunoassay procedure for plasma 11-deoxycortisol (S) was developed using an antiserum prepared by immunizing rabbits with S-21-hemisuccinate bovine serum albumin and S-3-oxime-bovine serum albumin. Thereafter plasma S, cortisol (F) and adrenocorticotropic hormone (ACTH) responses to metyrapone were investigated in 13 normal adult males and 39 patients with prostatic cancer. The results were as follows: 1) The antiserum against S-3-oxime-bovine serum albumin had less cross reactivity (less than 10%) with other steroids than that against S-21-hemisuccinate bovine serum albumin and obtained a good standard curve. The intra-assay variance and interassay variance of this method using the former antiserum (N = 10) were 12.4% asd 14.9% respectively, and the blank value was 3.7 +/- 1.6 pg. 2) Basal levels of S. F and ACTH in plasma from 13 normal adult males, ranged 21 approximately 80 years, old, were 98.4 +/- 15.7 ng/dl (mean value +/- S.E.), 12.7 +/- 0.78 micrograms/dl and 30.6 +/- 3.02 pg/ml respectively. Those level increased to 7060 +/- 598 ng/dl, 24.3 +/- 1.69 micrograms/dl and 24.3 +/- 1.6 pg/ml at 9 a.m. following oral administration of metyrapone (30 mg/kg b.w.) at midnight. 3) Both basal levels and responses of plasma S and F to metyrapone increased remarkably, while those of ACTH were within the normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and AC normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and AC normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and ACTH responses to metyrapone were unchanged compared to normal adult males 2 approximately 4 weeks after discontinuation of the therapy, and this data suggested that estrogens had no inhibitory effect on the pituitary-adrenal axis. However, in cases treated with progestational agents over a long-term period, plasma S and ACTH responses to metyrapone decreased slightly but returned to the normal range 2 approximately 4 weeks after discontinuation of the therapy. This suggested that the inhibitory effect of these agents on the pituitary-adrenal axis was mild and reversible.

A case of prostatic phyllodes tumor which developed in a 78-yr-old man is reported. Histologically, the tumor comprised myxomatous and cellular portions with a proliferation of atypical stromal cells. Multinucleated giant cells were occasionally present, but mitoses were rare. Fibroblastic differentiation of the tumor cells was confirmed by numerous rough endoplasmic reticulums and free ribosomes, and by immunoreactivity for vimentin. Approximately one-third of the tumor cells showed estrogen-receptor immunoreactivity at their nuclei. The patient is well, with no evidence of tumor recurrence, five years after the resection. The tumor was diagnosed as being a benign prostatic phyllodes tumor showing fibroblastic differentiation, and of an estrogen-dependent nature.

Twenty-four patients, each with advanced bladder cancer (BC) or brain tumor (BT), were treated by intraarterial infusion of angiotensin II in combination with DDP as the main drug together with other anticancer drugs. As for the frequency of treatment by the intraarterial therapy, only one course was given in 15 cases, two courses in 9 (BC), one course in 21 cases, and two courses in 3 (BT). CR was obtained in ten of 24 evaluable patients with BC and PR in eleven. Of 20 evaluable patients with BT, 3CRs and 7PRs were attained. The selective enhancement of tumoral blood flow induced by regionally infused angiotensin II was observed using continuous intraarterial infusion of krypton-81 m.

Intra-arterial infusion chemotherapy in combination with angiotensin II was performed in 5 patients with advanced bladder cancer (all T3M0). The infusion catheter was inserted from a femoral artery into the internal iliac artery. The basic dosage was 70 mg/m2 of Cis-diammine-dichloroplatinum (CDDP) and 40 mg/m2 of Adriamycin (ADM) or 4'-0-tetrahydropyranyl-ADM (THP) in combination with 20-40 micrograms angiotensin II over a total duration of 20 minutes for both sides. Of the 5 patients, 3 CR and 2 PR were obtained by only one or two courses of intra-arterial infusion chemotherapy. Histological examination showed no viable cells in the three CR cases. Intra-arterial infusion chemotherapy in combination with angiotensin II may thus be clinically useful for advanced bladder cancer.