Biomedical subjects

J Nakashima

Publications and source records attributed to J Nakashima.

At least 19 recordsLinked to original sources

PubMed1997

Effects of endocrine therapy on the primary lesion in patients with prostate carcinoma as evaluated by endorectal magnetic resonance imaging.

BACKGROUND: Little effort has been made at the quantitative and qualitative evaluation of patients with prostate carcinoma, including downsizing and downstaging of the primary lesion, after conservative therapy. The current study was undertaken to investigate the qualitative and quantitative effects of endocrine therapy on the primary prostate carcinoma using magnetic resonance imaging (MRI). METHODS: The primary prostate carcinoma was evaluated by endorectal MRI approximately 4 months after the initiation of endocrine therapy in 48 patients with histologically confirmed prostate carcinoma detected by endorectal MRI before therapy. RESULTS: The volumes of the prostate gland, the carcinoma, and the noncarcinomatous components were reduced to 60.2 +/- 2.7%, 25.5 +/- 2.9%, and 83.2 +/- 6.3% of their pretreatment volumes respectively after endocrine therapy, indicating that the tumors are more susceptible to endocrine therapy than the nontumorous components. The number of prostate carcinomas that demonstrated low signal intensity compared with the normal peripheral zone on T2-weighted images decreased after endocrine therapy and the number of carcinomas with enhancement of T1-weighted contrast-enhanced images increased after therapy. Seven of the 48 patients underwent downstaging after endocrine therapy, based on the endorectal MRI evaluation. CONCLUSIONS: The results of the current study suggest that downsizing and occasionally downstaging of the carcinoma may occur after endocrine therapy in patients with prostate carcinoma. In addition, the androgen sensitivity of the prostate carcinoma tissue is relatively high compared with the residual noncancerous prostate gland.

Antineoplastic Agents, Hormonal↗

PubMed1997

Constitutive production of multiple cytokines and a human chorionic gonadotrophin beta-subunit by a human bladder cancer cell line (KU-19-19): possible demonstration of totipotential differentiation.

Bladder cancer cells have been shown to secrete a variety of factors that are not related to cells of urothelial origin. The histogenesis of these tumour developments is uncertain, and a variety of theories have been previously reported. In the present manuscript, we identify the factors constitutively produced by a human bladder cancer cell line (KU-19-19) that was found to produce beta human chorionic gonadotrophin (beta-hCG), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1alpha (IL-1alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). The cells were obtained from a case of metastatic carcinoma that was originally diagnosed to be a grade 3 (WHO classification), invasive transitional cell carcinoma of the bladder. On microscopic observation, the cultured cells exhibited an epithelial appearance with vacuole formation in their cytoplasm. Ultrastructural observations revealed relatively marked microvilli and a tight junction. Significant amounts of beta-hCG, G-CSF, GM-CSF, IL-1alpha, IL-6 and IL-8 concentrations in the supernatant from cultured cells were demonstrated by enzyme-linked immunosorbent assays, while the expression of mRNA of these marker proteins in cancer cells was also significantly exhibited by reverse transcription polymerase chain reaction (RT-PCR). In addition, the expression of G-CSF receptor and IL-6 receptor mRNA was also shown by RT-PCR. Xenograft transplantability using nude mice was observed in association with the presence of severe neutrophilia in the peripheral blood. These results indicate that this cell line appears to be an effective model for the study of transitional cell carcinoma of the bladder with multipotent differentiation potentials.

Aged↗

PubMed1997

Role of reactive oxygen species in cis-dichlorodiammineplatinum-induced cytotoxicity on bladder cancer cells.

This study was undertaken to investigate the intracellular induction of reactive oxygen species (ROS) by cis-dichlorodiammineplatinum (CDDP) and the augmentation of their cytotoxicity in bladder cancer cells (KU7) by enhancement of ROS generation by the glutathione (GSH) depletors buthionine sulphoximine (BSO) and diethylmaleate (DEM). CDDP-induced cytotoxicity in KU7 cells and its modulation by GSH depletors were determined using spectrophotometric measurement with crystal violet staining. The effects of GSH depletors on intracellular GSH levels were confirmed using the GSH reductase-DTNB recycling method. Intracellular ROS generation induced by CDDP with or without GSH depletors was estimated from the amount of intracellular dichlorofluorescein (DCF), an oxidized product of dichlorofluorescein (DCFH), which was measured with an anchored cell analysis and sorting system. The cytotoxic effects of CDDP (IC50 15.0 +/- 2.5 microM) were significantly enhanced by BSO (IC50 9.3 +/- 2.6 microM, P < 0.01) and DEM (IC50 10.3 +/- 0.3 microM, P <0.01). BSO and DEM produced a significant depletion in intracellular GSH levels (9.6 +/- 0.4 nmol 10(-6) cells, 17.9 +/- 1.0 nmol 10(-6) cells) compared with the controls (30.5 +/- 0.6 nmol 10(-6) cells). Intracellular DCF production in KU7 cells treated with CDDP (1.35 +/- 0.33 microM) was significantly enhanced by the addition of BSO (4.43 +/- 0.33 microM) or DEM (3.12 +/- 0.22 microM) at 150 min. These results suggest that ROS may play a substantial role in CDDP-induced cytotoxicity and that GSH depletors augment its cytotoxicity through an enhancement of ROS generation in bladder cancer cells.

Antimetabolites↗

PubMed1997

A transient increase in serum procollagen 1 carboxyterminal peptide following effective treatment in prostate cancer patients with bone metastases.

Procollagen 1 carboxyterminal peptide (P1CP) is thought to be an indicator of new bone formation. The present report demonstrates that effective endocrine therapy induced an initial increase followed by a delayed decrease in serum levels of P1CP and alkaline phosphatase in spite of an immediate decrease in serum PSA and PAP and improvement of clinical symptoms in prostate cancer patients with bone metastases. The transient increase in P1CP and alkaline phosphatase is a healing reaction and is followed by apparent improvement. Short-term effects of endocrine therapy on prostate cancer patients with bone metastases should be comprehensively evaluated based upon the entire spectrum of clinical and laboratory findings including serial changes of serum prostate markers and bone markers as well.

Adenocarcinoma↗

PubMed1997

ACTH-independent bilateral macronodular adrenocortical hyperplasia caused Cushing's syndrome.

A 53-year-old man who had been followed up for the treatment of hypertension presented with a bilateral adrenal mass during a screening CT scan. Other imaging studies and biochemical tests suggested Cushing's syndrome caused by a pituitary-independent and adrenal-dependent bilateral adrenal tumor. A total adrenalectomy was performed and the pathological appearance of the surgical specimen showed adrenal hyperplasia. Therefore, these findings were considered to be consistent with ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH). This tumor is quite rare and its etiology still remains controversial. We herein report this incidentally found AIMAH and also review the pertinent literature.

Adrenal Glands↗

PubMed1997

Clinical experience with incidentally discovered pheochromocytoma.

PURPOSE: We reviewed 17 resected pheochromocytomas comprising 7 from symptomatic patients, and 10 unsuspected and incidentally discovered tumors. We compared various parameters concerning these 2 groups and investigated the features of the incidentally discovered pheochromocytoma. MATERIALS AND METHODS: Patient gender and age, clinical symptoms and signs, tumor localization, detection methods, findings on imaging studies, urinary catecholamine concentrations, results of metoclopramide stimulation tests, treatments at operation and tumor size were evaluated. Furthermore, we compared the clinically diverse aspects arising between the symptomatic and incidentally discovered pheochromocytomas. RESULTS: The 24-hour urinary noradrenaline and vanillylmandelic acid levels in the incidental cases tended to be lower than those in the symptomatic cases, while 24-hour urinary dopamine was significantly less (468 +/- 221 compared to 1,558 +/- 899 microg./day, respectively). Typical symptoms of pheochromocytoma were noted in 6 patients (60%) in the incidental tumor group. The incidental cases had a markedly high false-negative rate (71%) as noted by the metoclopramide stimulation test, although the symptomatic cases had a 100% positive rate. On the other hand, the average diameter of incidental tumors was significantly larger than that of the symptomatic lesions (55.5 +/- 19.1 versus 35.9 +/- 12.1 mm., respectively). CONCLUSIONS: Clinical signs and findings in patients with incidental tumors were weaker than those with symptomatic disease although most incidental tumors functioned. Lower urinary catecholamine values in the incidental tumors were consistent with these results. However, the surgical risk for incidental tumors was the same as that for symptomatic lesions. Therefore, patients with incidentally discovered pheochromocytomas scheduled to undergo surgery should be treated accordingly.

Adolescent↗

PubMed1997

The value of serum carboxyterminal propeptide of type 1 procollagen in predicting bone metastases in prostate cancer.

PURPOSE: Carboxyterminal propeptide of type 1 procollagen (P1CP) is believed to be a marker of new bone formation. We investigated the possible application of serum P1CP as a biochemical marker for bone metastases in patients with prostate cancer. MATERIALS AND METHODS: Prostate specific antigen (PSA), prostatic acid phosphatase (PAP), P1CP and alkaline phosphatase were measured in 136 serum samples from 79 patients with untreated prostate cancer, 29 with stage D2 disease in remission and 28 with progressive stage D2 carcinoma. RESULTS: Serum P1CP and alkaline phosphatase were significantly elevated in untreated patients with a positive bone scan (278.9 +/- 61.9 ng./ml. and 826.5 +/- 176.3 international units per 1., respectively) compared to those with a negative bone scan (104.2 +/- 4.2 and 200.8 +/- 9.1, respectively, p <0.05). The areas under receiver operating characteristics curves were 0.86 for P1CP, 0.87 for alkaline phosphatase, 0.88 for PSA and 0.85 for PAP. The best accuracy rates for P1CP, alkaline phosphatase, PSA and PAP to predict bone lesions were 84, 87, 86 and 84%, respectively. P1CP provided a greater specificity and positive predictive value. These serum markers correlated significantly with the extent of disease on bone scan (p <0.05). The incidence of positive serum P1CP and alkaline phosphatase decreased significantly in response to endocrine therapy in patients with bone metastasis, and increased progressively in association with progression of the tumor (p <0.05) parallel to PSA and PAP. CONCLUSIONS: These findings suggest that serum P1CP is a useful indicator for predicting bone metastases.

Aged↗

PubMed1996

Client self-determination and professional intervention: striking a balance.

Social workers find themselves caught in the cross fire between two imperatives: (1) outcome-oriented and competency-based practice requisites and (2) the principle of client self-determination. In this context, the authors hypothesize that social workers use a wide range of gradations along a continuum of practice directiveness. Furthermore, there is ethical justification for this diverse role repertoire. Directiveness modalities are influenced by specific conditional factors that guide practitioner behavior. A study is described that empirically explores and amplifies these hypotheses.

Adult↗

PubMed1995

Tumor necrosis factor and coagulopathy in patients with prostate cancer.

This study was undertaken to evaluate the relationship between serum tumor necrosis factor (TNF) and coagulopathy in patients with prostate cancer. TNF levels in 104 sera obtained from 101 prostate cancer patients were determined using an enzyme immunoassay. Serum levels of fibrin/fibrinogen degradation product E fragment (FDP) and plasma levels of fibrin degradation product D-dimer in patients with elevated serum TNF levels were 1221.95 +/- 375.94 ng/ml and 27.34 +/- 9.81 micrograms/ml, which were significantly higher than those (FDP, 94.35 +/- 13.17 ng/ml; D-dimer, 1.03 +/- 0.20 micrograms/ml) in patients with undetectable serum TNF levels (P < 0.01). In addition, patients with elevated serum TNF levels showed significant increases in plasma levels of thrombin-antithrombin-III complex and plasmin-alpha 2-antiplasmin inhibitor complex and a significantly higher incidence of positive plasma soluble fibrin monomer complex than did those with undetectable serum TNF levels. The percentage of prothrombin time was significantly decreased in the group with elevated serum levels of TNF. Serum levels of TNF were significantly elevated in patients with serum FDP levels of > or = 200 ng/ml than in those with serum FDP levels of < 200 ng/ml (3.91 +/- 0.45 versus 2.17 +/- 0.08 units/ml) and in patients with plasma D-dimer levels of > or = 2 micrograms/ml than in those with plasma D-dimer levels of < 2 micrograms/ml (3.82 +/- 0.48 versus 2.10 +/- 0.06 units/ml). These results suggest that TNF may be one of the pathogenetic factors that could explain the occurrence of coagulopathy in patients with prostate cancer.

Adenocarcinoma↗

PubMed1995

MRI evaluation of cavitation induced by laser prostatectomy.

Magnetic resonance images obtained by endorectal surface coils have shown histopathological changes in the prostate. In patients who underwent laser prostatectomy, MR imaging demonstrated how deeply the laser energy penetrated and how different changes were induced by the coagulation and vaporization techniques. Cavitation effects were quantitatively analyzed, and the processes of reepithelization after sloughing of necrotic tissues were observed in gadolinium-enhanced T1-weighted images.

Aged↗

PubMed1995

Establishment of a human cell line secreting neuron-specific enolase from a primitive neuroectodermal tumor of the retroperitoneal cavity.

Primitive neuroectodermal tumor (PNET) is one of the small round cell malignancies of presumed neural crest origin for which an effective treatment has not yet been established. In the present study, a human cell line, designated KU-9, was established from a 27-year-old male patient with PNET of the retroperitoneal cavity and has been successfully maintained in nude mice and in culture. On histological examination, the primary tumor was composed of poorly differentiated small round cells arranged in clusters showing a variety of mitotic changes, and contained Homer-Wright rosettes. The histopathological appearance of the KU-9 xenografts was similar to that of the primary tumor. Electron microscopy revealed neurosecretory granules and cytoplasmic processes in the xenograft. No significant amplification of N-myc gene was observed in the KU-9 cells. The KU-9 cells showed chromosome numbers ranging from 56 to 61 with consistent structural abnormalities being add(2)(q31), +add(11)(p11.2), +add(13)(p11.1), and +del(22)(q12). Cultured KU-9 cells grew exponentially with a doubling time of about 50 h and a time-dependent increase in medium levels of neuron-specific enolase (NSE) was noted. Serum levels of NSE in KU-9 tumor-bearing nude mice were significantly elevated and a linear relationship between the serum NSE levels and the tumor NSE content or tumor volume was observed, suggesting that serum levels of NSE may reflect the PNET tumor burden and tumor extent. These results indicate that the KU-9 cell line provides a reproducible model system which could be useful in gaining some insight into the histogenesis and oncogenesis of PNET and in establishing an effective treatment for PNET.

Adult↗

PubMed1995

Retroperitoneal Ewing's sarcoma.

We report a case of extraskeletal Ewing's sarcoma arising in the retroperitoneal cavity. The tumor was excised en bloc with the left kidney and infiltrated portion of the left ureter. Histological diagnosis was confirmed by both electron micrography and immunohistochemical staining using a newly developed mouse monoclonal antibody 5C11, which specifically reacts with Ewing's sarcoma. An adjuvant chemotherapy T-11 regimen has been successfully preventing the recurrence.

Adult↗

PubMed1995

[Clinical efficacy of methotrexate, vinblastine, doxorubicin and cisplatin adjuvant chemotherapy following radical surgery for locally invasive urothelial cancers: long-term results].

Determined were long-term results of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) adjuvant chemotherapy following radical surgery for locally invasive urothelial cancers. All cases at least histologically exhibited one of the following findings, a stage beyond pT3b (bladder cancer) or pT3 (upper tract urothelial cancer), lymph duct tumor involvement (ly +), venous involvement (V +), and/or regional lymph node involvement (N1) without any evidence of distant metastasis and/or residual tumors. Two cycles of M-VAC chemotherapy were given after radical surgery for each case. A total of 33 cases comprising 21 bladder cancers and 12 upper tract urothelial cancers following cystectomy and/or nephroureterectomy with partial cystectomy who had a mean follow-up period of 56.7 +/- 9.2 months could be analyzed. Overall actuarial survival rates of three- and five-years estimated by Kaplan-Meier method were respectively 41.9% and 31.6%. These results indicate that the postoperative outcome was extremely poor in patients with locally advanced urothelial cancer even after extensive adjuvant chemotherapy. Therefore, more effective modalities including optimal dose and scheduling of chemotherapy are needed to assure therapeutic improvement of locally invasive urothelial cancers.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Magnetic resonance imaging following microwave thermotherapy, laser ablation and transurethral resection in patients with BPH.

Morphologic changes in hyperplastic prostate tissue following three different treatments were analysed by MRI using an endorectal surface coil. In cases treated by TUMT, the MRI findings of the prostate showed hemorrhagic necrosis, which was absorbed in 12 weeks, and a widened prostatic urethra. In cases treated by laser ablation, the thermal effect went deep, causing necrotic changes, and it took more than 8 weeks for the tissue to be shed and re-epithelization completed. In TURP, degenerative changes were seen only near the surface following mass reduction of the hyperplastic tissue, and the capsule shrinkage resulted in normalization of the prostatic urethra. It is suggested that improvement of the other parameters, such as IPSS and peak flow, in patients with obstructive BPH basically depends on these morphologic changes shown by MRI.

Aged↗

PubMed1995

Enhancement of erythropoietin production by selective adenosine A2 receptor agonists in response to hypoxia.

The purpose of this study was to characterize the effects of two new adenosine A2 agonists, 2-(p-(2-carboxyethyl)phenethyl amino)-5'-N-ethylcarboxamidoadenosine (CGS-21680) and N6-(2(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl)-adenosine (DPMA), on erythropoietin (EPO) production in vivo and in vitro. Intravenous injections of CGS-21680 (100 to 500 nmol/kg mouse/day) and DPMA (50 to 500 nmol/kg mouse/day) for 4 days produced significant increases in serum levels of EPO in exhypoxic polycythemic mice. CGS-21680 (10(-7) to 10(-6) mol/L) and DPMA (10(-8) to 10(-5) mol/L) also produced significant increases in medium levels of EPO in a cloned EPO-producing Hep3B hepatocellular carcinoma cell line after 18 hours of incubation in 1% O2. Both compounds also increased cellular cAMP levels significantly in a dose-dependent manner after 1 hour of incubation. A2 receptor binding assays with tritiated CGS-21680 revealed a single type of adenosine receptor binding site on Hep3B cell membranes with a dissociation constant of 132.9 nmol/L and a binding capacity of 270.6 fmol/mg protein. The Ki competition binding values versus tritiated CGS-21680 were 217 nmol/L for CGS-21680 and 86.8 nmol/L for DPMA. These results indicate that adenosine A2 receptor activation amplifies EPO production in response to hypoxia, both in vivo and in vitro.

Adenosine↗

PubMed1994

Adenosine A2 receptor modulation of erythropoietin secretion in hepatocellular carcinoma cells.

The present studies were undertaken using a cloned erythropoietin (Ep) producing hepatocellular carcinoma cell line (Hep3B) to attempt to correlate the receptor binding properties and biological activities of 5'-N-ethylcarboxamideadenosine (NECA), N6-cyclohexyladenosine (CHA) and N6-cyclopentyldenosine (CPA). Ep and cAMP levels in cultures of Hep3B cells in response to these adenosine analogues were measured by radioimmunoassay. Receptor binding affinities of the adenosine analogues were determined by measuring inhibition of binding of [3H] NECA to Hep3B cell membranes. Scatchard analysis of [3H]NECA to Hep3B cell membranes. Scatchard analysis of [3H]NECA binding to Hep3B cell membranes indicates a single class of binding sites with a dissociation constant of 431 nM and a binding capacity of 573 fmol/mg protein. The adenosine analogues tested produced a significant increase in Ep secretion and cAMP accumulation (ED50 for cAMP accumulation, NECA = 3.3 x 10(-7) M, CHA = 4.2 x 10(-6) M, CPA = 2.2 x 10(-6) M). In addition, NECA showed a higher binding affinity (Ki, 3.8 x 10(-7) M) for Hep3B cell membranes in comparison with CHA (Ki, 6.3 x 10(-6) M) and CPA (Ki, 3.9 x 10(-6) M). These results indicate that the rank order for potency for NECA, CHA and CPA in their binding to Hep3B cell membrane receptors correlates very well with their biological effects on Ep secretion and cAMP accumulation in Hep3B cells.

Adenosine↗

PubMed1994

Flow cytometric bromodeoxyuridine/deoxyribonucleic acid bivariate analysis for predicting tumor invasiveness of upper tract urothelial cancer.

We previously reported that flow cytometric bromodeoxyuridine/deoxyribonucleic acid (DNA) bivariate analysis can provide important information on the malignant potential of bladder cancer. Therefore, in the current study we further evaluated upper tract urothelial tumors to clarify whether DNA/bromodeoxyuridine bivariate analysis can provide additional prognostic information on patients with upper tract urothelial tumor. A total of 43 upper tract urothelial tumors that were resected by nephroureterectomy was analyzed. Flow cytometric DNA ploidy and bromodeoxyuridine labeling were determined by an in vitro bromodeoxyuridine labeling method. DNA diploid tumors were associated with an 85.9% 3-year survival rate compared to 36.5% for DNA aneuploid tumors. On the other hand, 11 high bromodeoxyuridine labeled tumors demonstrated a 16.4% 3-year survival rate compared to 82.4% for those with low bromodeoxyuridine labeled tumors. Multivariate survival analysis using the Cox proportional regression model was performed to identify the most informative factors for prognosis, with the single most important factor being histological tumor stage. Nearly as important and the next factor to be chosen was tumor grade, followed by bromodeoxyuridine labeling index status. DNA ploidy status did not influence clinical outcome. Thereafter, when actuarial 3-year survival rates according to the bromodeoxyuridine labeling index status in grade 3 tumors were estimated, 68.4% and 16.7% 3-year survival rates were observed in cases of low and high bromodeoxyuridine labeling index tumors, respectively. These results indicate that flow cytometric bromodeoxyuridine/DNA bivariate analysis may be useful in dividing patients with grade 3 upper tract urothelial carcinoma into 2 different prognosis groups.

Bromodeoxyuridine↗

PubMed1994

Primitive neuroectodermal tumor of the retroperitoneal cavity.

We report a case of primitive neuroectodermal tumor (PNET) arising from the retroperitoneal cavity. Because of infiltration, the tumor was excised en bloc with the left kidney. Despite postoperative adjuvant chemotherapy and local radiation therapy, the tumor recurred and the patient died of the disease 3 months postoperatively. Serum levels of neuron-specific enolase (NSE) correlated with those of lactate dehydrogenase (LDH), and it is suggested that monitoring NSE and LDH is useful in evaluating tumor recurrence. The clinical course and the treatment of this aggressive tumor are reviewed.

Adult↗