[A case of liver metastasis of the non-functioning islet cell tumor of the pancreas treated by percutaneous ethanol injection therapy].
Explore the source record for details and available documents.
Adenoma, Islet Cell↗
Biomedical subjects
T Tominaga
Publications and source records attributed to T Tominaga.
Circulating soluble Fas concentration in breast cancer patients.
Fas/Fas ligand (FasL) system, a major regulator of apoptosis, is involved in cancer cell death induced by the immune system and anticancer drugs. Fas is a cell-surface receptor that exists in two forms, transmembrane and soluble. The former induces apoptosis by ligation of FasL or agonistic anti-Fas antibody, whereas the latter inhibits Fas-mediated apoptosis by neutralizing its ligand. In this study, we examined circulating soluble Fas (sFas) concentration in 118 healthy people, 162 primary and 71 recurrent breast cancer patients by ELISA. In the healthy group, men showed higher sFas concentrations than women (P<0.001). In both sexes, sFas levels increased with age, and the age-matched cutoff value was determined. The median sFas concentration in primary and recurrent cancer patients was 0.815 and 1.510 ng/ml, both of which were higher than in normal female controls (0.580 ng/ml; P = 0.024 and P<0.001, respectively). Among primary cancer patients, although no significant correlation was found between sFas concentration and clinical parameters other than menopausal status, high-sFas patients had a worse prognosis than low-sFas patients for both overall and disease-free survival (P = 0.013 and P = 0.032, respectively). The multivariate analysis confirmed that circulating sFas concentration was an independent prognostic indicator (P = 0.020 for overall survival, P = 0.025 for disease-free survival). We looked at the recurrent cancer patients, and sFas levels were higher in patients with liver metastasis compared with those with other recurrent sites (P = 0.010), and high-sFas patients showed a worse prognosis than low-sFas patients (P = 0.037). Our data demonstrate that, compared with healthy female controls, breast cancer patients, especially those with liver metastases, have higher circulating sFas levels. sFas may be useful once these results are confirmed by larger studies.
Adult↗
p160ROCK mediates RhoA activation of Na-H exchange.
The ubiquitously expressed Na-H exchanger, NHE1, acts downstream of RhoA in a pathway regulating focal adhesion and actin stress fiber formation. p160ROCK, a serine/threonine protein kinase, is a direct RhoA target mediating RhoA-induced assembly of focal adhesions and stress fibers. Here, stress fiber formation induced by p160ROCK was inhibited by the addition of a specific NHE1 inhibitor, ethylisopropylamiloride, in CCL39 fibroblasts, and was absent in PS120 mutant fibroblasts lacking NHE1. In CCL39 cells, NHE1 activity was stimulated by expression of mutationally active p160ROCK, but not by mutationally active protein kinase N, another RhoA target kinase. Expression of a dominant interfering p160ROCK inhibited RhoA-, but not Cdc42- or Rac-activation of NEH1. In addition, the p160ROCK-specific inhibitor Y-27632 inhibited increases in NHE1 activity in response to RhoA, and to lysophosphatidic acid (LPA), which stimulates RhoA, and it also inhibited LPA-increased phosphorylation of NHE1. A C-terminal truncation of NHE1 abolished both LPA-induced phosphorylation and activation of the exchanger. Furthermore, mutationally active p160ROCK phosphorylated an NHE1 C-terminal fusion protein in vitro, and this was inhibited in the presence of Y-27632. Phosphopeptide maps indicated that identical residues in NHE1 were phosphorylated by p160ROCK in vivo and in vitro. These findings identify p160ROCK as an upstream, possibly direct, activator of NHE1, and suggest that NHE1 activity and phosphorylation are necessary for actin stress fiber assembly induced by p160ROCK.
Actins↗
Solitary plasmacytoma in the thoracic spine. Two case reports.
Plasmacytoma of the spine is rather common, but solitary occurrence is not. We report two cases of solitary plasmacytomas in the thoracic spine. A 72 year old male and a 77 year old male presented with progressive paraparesis. In both cases, magnetic resonance images revealed tumors in the thoracic spine which predominantly occupied the posterior elements of the spine with compression of the spinal cord. Abnormal proteinuria and proteinemia were not detected. The tumors were removed and patients' symptoms improved, the tumors were diagnosed by histopathology to be plasmacytomas. Further neuroradiological studies suggested them to be single lesions, so that the final diagnosis was solitary plasmacytomas. Solitary plasmacytoma should be considered for diagnosis of single spinal lesion even without abnormal proteinemia or proteinuria.
Aged↗
Distribution and concentration of urocortin, and effect of adrenalectomy on its content in rat hypothalamus.
We developed a specific and sensitive radioimmunoassay (RIA) for rat urocortin (rUcn) and investigated the tissue distribution and concentration of immunoreactive (IR-)Ucn in rats. Antiserum was obtained by immunizing rabbits with synthetic rUcn21-35 coupled with bovine thyroglobulin. 125I-[Tyr]18-rUcn19-37 was used as the tracer. The RIA detected synthetic rUcn1-40 as low as 0.4 fmol/tube, and did not cross-react with other corticotropin-releasing factor-related peptides. IR-Ucn was widely distributed in central nervous system, endocrine organs, and digestive system. Its concentration was highest in pituitary (11.0 +/- 1.36 pmol/g.w.w., mean +/- SEM, n=4). Reverse-phase HPLC revealed that hypothalamic IR-Ucn had similar chromatographic mobility to synthetic rUcn1-40. However, bilateral adrenalectomy did not influence the hypothalamic IR-Ucn content. Our results suggest that Ucn may play important roles in various tissues in normal rats, but not behave as a hypothalamic hypophysiotropic factor in mediating adrenocorticotropin secretion in adrenalectomized rats.
Adrenal Glands↗
Effect of TYB-2285 on peritoneal anaphylaxis in passively sensitized rats.
1. The effect of TYB-2285, a novel anti-inflammatory drug, was investigated on passive peritoneal anaphylaxis in rats, and compared with disodium cromoglycate (DSCG), amlexanox, ketotifen fumarate and tranilast. 2. As parameters of passive peritoneal anaphylaxis, histamine release into the peritoneal cavity and capillary permeability elicited by ascitis were measured. 3. TYB-2285 (10 mg/kg), when given intraperitoneally at 0.5, 1 and 2 min before antigen challenge, inhibited anaphylactic histamine release by 36.2%, 57.5% and 52.6%, respectively. TYB-2285 also inhibited capillary permeability by 20.9%, 57.6% and 49.0%, respectively. 4. DSCG (10 mg/kg), given intraperitoneally 0.5 min before challenge, inhibited histamine release and capillary permeability by 79.6% and 57.6%, respectively. 5. Amlexanox (10 mg/kg), given intraperitoneally 0.5 min before challenge, inhibited histamine release and capillary permeability by 85.6% and 74.8%, respectively. 6. A time-course study showed that TYB-2285 (30 mg/kg) was effective for 30 min after oral administration. A dose-response study suggested that the inhibitory effect of TYB-22585 (postoperatively) on histamine release during PPA reached a plateau at 10 mg/kg. 7. In passive peritoneal anaphylaxis in vitro, TC-1121 and TC-1122, metabolites of TYB-2285, inhibited antigen-induced histamine release at 10(-7) to 10(-5) M in a dose-dependent manner, whereas TYB-2285 itself and other major metabolites of TYB-2285, TC-286 and TC-326, did not inhibit histamine release, even at 10(-4) M.
Anaphylaxis↗
Novel antiallergic and antiinflammatory agents. Part I: Synthesis and pharmacology of glycolic amide derivatives.
A series of mono-glycoloylamino derivatives was synthesized by treatment of the corresponding aromatic monoamine derivatives with glycoloyl chloride derivatives in pyridine or dichloromethane, in the presence of a base such as triethylamine or pyridine. Hydrolysis of acetoxy compounds in aqueous ammonia and methanol solution produced hydroxy derivatives with ease. These compounds were tested in the rat PCA (passive cutaneous anaphylaxis) assay by oral administration. Thiazole and thiadiazole derivatives showed moderate inhibition in this assay. In contrast, benzothiazole and benzonitrile derivatives exhibited marked inhibition. In particular, compound 5t also showed marked inhibition of eosinophil adhesion to TNF (tumor necrosis factor) -alpha-treated HUVEC (human umbilical vein endothelial cells) in the range of 10(-8)-10(-5) M.
Administration, Oral↗
Novel antiallergic and antiinflammatory agents. Part II: Synthesis and pharmacology of TYB-2285 and its related compounds.
A series of m-bis(glycoloylamino)benzene derivatives was synthesized by treatment of the corresponding m-diaminobenzene derivatives with glycoloyl chloride derivatives in pyridine. Hydrolysis of acetyl compounds gave hydroxy derivatives, from which other acyl derivatives could be synthesized. These compounds were tested in the rat PCA (passive cutaneous anaphylaxis) assay by oral administration. Benzonitrile derivatives (4c, 5c, 6c, 4h, 5h) exhibited notable inhibition in this assay. Compounds 5c and 6c also showed remarkable inhibition of eosinophil adhesion to TNF- (tumor necrosis factor) alpha-treated HUVEC (human umbilical vein endothelial cells) in the range of 10(-8)-10(-5) M. Compound 5c is now under investigation in Japan as TYB-2285 (Figure 1) for asthma and atopic dermatitis in phase II clinical studies.
Administration, Oral↗
Phase II study of paclitaxel (BMS-181339) intravenously infused over 3 hours for advanced or metastatic breast cancer in Japan. BMS-181339 Breast Cancer Study Group.
A Phase II study of paclitaxel in patients with primary advanced or metastatic breast cancer was conducted by a cooperative study group consisting of 16 institutions in Japan. Paclitaxel at a dose of 210 mg/m2 was intravenously infused over 3 hours, along with premedication to prevent hypersensitivity reactions. The course was repeated at 21-day intervals. Of 62 eligible patients, 60 were evaluable for toxicity and 59 were evaluable for efficacy. Forty-five patients were previously treated with anthracyclines. Twenty-one of 59 patients (35.6%) had a major objective response including 2 CRs and 19 PRs (95% confidence interval, 23.6-49.1%). A response rate of 35.5% (CR1, PR10) was observed in 31 patients refractory to the anthracyclines containing prior metastatic chemotherapy. Median (range) time was 41 (6-100) days to onset of and median duration of response was 125 (36-305) days. Toxicities included leukopenia (grade 3, 4: 67%), anemia (grade 1-3: 80%), thrombocytopenia (grade 1: 8%), alopecia (grade 3: 43%), peripheral neuropathy (grade 1-3: 93%), arthralgia (59%), myalgia (46%), nausea and vomiting (40%), fever (33%), allergic reaction (grade 3: 2%) and hypotension (grade 3: 5%). All toxicities were tolerable and manageable. Paclitaxel intravenously infused over 3 hours demonstrated a significant antitumor activity for metastatic breast cancer. Furthermore, paclitaxel exhibited non-cross resistance to anthracycline. Paclitaxel administered as a convenient 3-hour infusion is effective for patients with metastatic breast cancer and has an acceptable toxicity profile.
Adult↗
Metalloproteinases and tissue inhibitors of metalloproteinases.
Because the proteolytic degradation of extracellular matrix is required for invasion and metastasis, it would appear that the important family of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) might be prognostic indicators of the invasive potential of a breast tumor. Nevertheless, there are few data demonstrating an independent prognostic value of any individual MMPs or TIMPs in primary breast cancer patients. It is possible, however, that the balance among levels of certain MMPs and their inhibitors will be more informative, since MMPs are clearly involved in paracrine tumor-stromal interactions and are associated with angiogenesis, which does appear to be prognostic.
Breast Neoplasms↗
Stimulatory effect of calcitonin gene-related peptide on adrenocorticotropin release from rat anterior pituitary cells.
In the present study, we examined the direct regulatory effect of rat calcitonin gene-related peptide (CGRP) on adrenocorticotropin (ACTH) release from rat cultured anterior pituitary cells. CGRP significantly increased ACTH release at concentrations of 10(-8)-10(-11) M. The ACTH release was gradually increased by CGRP concentrations lower than 10(-10) M, and was decreased at concentrations higher than 10(-9) M, presenting a bell-shaped dose-response curve. As well as having an additive effect on corticotropin-releasing factor-induced ACTH release, CGRP stimulated the accumulation of intracellular cAMP. The CGRP-induced ACTH release was inhibited by a protein kinase A inhibitor, suggesting that its stimulatory effect on the ACTH release was mediated via an adenylate-cyclase-protein kinase system. CGRP-like immunoreactive nerve fibers have been reported to innervate the anterior pituitary, so that the stimulatory effect of CGRP on the ACTH release suggests that this peptide may be involved in neural regulation of hormone secretion in the anterior pituitary.
Adrenocorticotropic Hormone↗
Na-H exchange acts downstream of RhoA to regulate integrin-induced cell adhesion and spreading.
The ubiquitously expressed Na-H exchanger NHE1 functions in regulating intracellular pH and cell volume. NHE1 activity is stimulated by hormones, growth factors, and activation of integrin receptors. We recently determined that NHE1 activity is also stimulated by activation of the low molecular weight GTPase RhoA and that increases in NHE1 activity are necessary for RhoA-induced formation of actin stress fibers. We now show that NHE1 acts downstream of RhoA to modulate initial steps in integrin signaling for the assembly of focal adhesions. Adhesion of CCL39 fibroblasts on fibronectin was markedly delayed in the presence of the NHE inhibitor ethylisopropylamiloride. In mutant PS120 cells, derived from CCL39 fibroblasts but lacking NHE1, adhesion was also delayed but was rescued in PS120 cells stably expressing NHE1. In the absence of NHE1 activity, cell spreading was inhibited, and the accumulation of integrins, paxillin, and vinculin at focal contacts was impaired. Additionally, tyrosine phosphorylation of p125(FAK) induced by integrin clustering was also impaired. Inactivation of RhoA with C3 transferase and inhibition of the Rho-kinase p160ROCK with the pyridine derivative Y-27632 completely abolished activation of NHE1 by integrins but not by platelet-derived growth factor. These findings indicate that NHE1 acts downstream of RhoA to contribute a previously unrecognized critical signal to proximal events in integrin-induced cytoskeletal reorganization.
Animals↗
Cyclophosphamide, adriamycin, 5-fluorouracil and high-dose toremifene for patients with advanced/recurrent breast cancer. The Japan Toremifene Cooperative Study Group.
BACKGROUND: Multi-combination chemotherapy consisting of anthracyclines has been effective but has not invariably prolonged the survival period in advanced/recurrent breast cancer. The possibility has been discussed that chemoendocrine therapy combined with endocrine agents is more effective. METHODS: In order to evaluate the toxicity and efficacy of a new endocrine therapy for advanced/recurrent breast cancer, we ran a pilot study during the period from July 1994 to July 1996. RESULTS: Twenty-two patients with advanced/recurrent breast cancer were treated with chemoendocrine therapy consisting of cyclophosphamide (100 mg/body) p.o. daily for 14 days, with adriamycin (40 mg/m2) i.v. and 5-fluorouracil (500 mg/body) i.v. on day 1 (repeated every 3 weeks for 9 weeks) (CAF therapy), and high-dose toremifene (120 mg/body) p.o. daily. Of 20 evaluable patients, two showed complete response (10%), eight partial response (40%), six no change (30%) and four progressive disease (20%). The overall response rate was 50%, and the median duration of response was 69.5 days (28-133+ days). The major toxicities were drug-induced alopecia, gastrointestinal toxicity and hematological toxicity, but these were clinically well tolerated. No serious cardiac, liver or renal symptom was seen. CONCLUSIONS: Based on these results, we consider the addition of high-dose toremifene to the CAF therapy to be useful in the treatment of advanced and recurrent breast cancer.
Adult↗
Production and secretion of endothelin-1 by cultured choroid plexus carcinoma cells.
Choroid plexus carcinoma is a rare neoplasm derived from the epithelium of the choroid plexus. The production and secretion of endothelin-1 (ET-1) by cultured human choroid plexus carcinoma cells were studied by radioimmunoassay and Northern blot analysis. Immunoreactive (IR)-ET was detected in the culture medium (2.78 +/- 0.12 fmol/10(5) cells/24 h; n = 5; mean +/- SEM) but not in the unconditioned medium. Reverse-phase high-performance liquid chromatography of the extract of the culture medium showed a single peak eluting in the position of ET-1. Treatment with tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) or a combination of interferon-gamma (IFN-gamma), TNF-alpha, and IL-1 beta caused significant increases in the IR-ET levels in the culture medium. Northern blot analysis of total RNA showed the expression of ET-1 mRNA in choroid plexus carcinoma cells. The expression levels of ET-1 mRNA were increased by treatment with a combination of IFN-gamma, TNF-alpha, and IL-1 beta. The present study has shown the production and secretion of ET-1 by cultured human choroid plexus carcinoma cells and suggests the possibility that ET-1 formation is related to the pathophysiology of this tumor.
Blotting, Northern↗
Influence of alcohol on branched-chain amino acid/tyrosine molar ratio in patients with cirrhosis.
We investigated whether the reduction of plasma tyrosine in alcoholic liver disease would affect the branched-chain amino acid/tyrosine molar ratio (BTR) measured using an enzymatic assay method in alcoholic cirrhosis. BTR values were higher in patients with compensated and decompensated alcoholic cirrhosis (5.68 +/- 2.29 and 3.28 +/- 0.75) due to reduction of the tyrosine level relative to those in patients with nonalcoholic cirrhosis (3.64 +/- 1.22 and 2.53 +/- 0.99). A decrease in tyrosine level and an increase in BTR value were observed after single ethanol administration to healthy subjects. As significant elevation of serum immunoreactive insulin levels followed elevation of serum glucose levels after alcohol loading, it was thought that insulin accelerated intrahepatic metabolism of aromatic amino acids, resulting in reduction of the tyrosine level. The same mechanism may be applied to tyrosine reduction in patients with alcoholic cirrhosis during heavy drinking.
Adult↗
Role of MDM2 overexpression in doxorubicin resistance of breast carcinoma.
Several oncoproteins or tumor suppressor gene products have been indicated to be of value as predictors of the de novo resistance to cytotoxic agents. In this study, we have investigated the role of MDM2 (murine double minutes) overexpression in doxorubicin resistance of breast cancer. Immunocytochemical analysis demonstrated that MDM2-positive tumors, even with p53-negative phenotype, were significantly more resistant to doxorubicin treatment compared to MDM2-negative tumors. An in vitro experimental model using stable mdm2-transfected MCF-7 cells carrying wild-type p53 confirmed that the cells become approximately 3-fold more resistant to doxorubicin as a result of MDM2 overexpression, and the wild-type p53 function, such as the induction of p21Waf1 following DNA damage, was significantly suppressed. MDM2 overexpression is suggested to be a novel marker for predicting lack of response to doxorubicin treatment in breast cancer patients.
Antibiotics, Antineoplastic↗
Role of apoptosis of thyrocytes in a rat model of goiter. A possible involvement of Fas system.
Apoptosis, a physiological process of cell death, may modulate the mass of the thyroid gland. We investigated the role of apoptosis and the possible involvement of Fas/Fas ligand (FasL) system in apoptosis during goiter formation and involution in a rat model of goiter. Rats were fed a low iodine diet and a goitrogen, 6-propyl-2-thiouracil, to induce goiter. Rats with goiter were then fed a high iodine diet to study the phase of involution. We examined the presence of apoptosis by electron microscopy (EM) and terminal deoxy-UTP nick end labeling (TUNEL). We also investigated the association between Fas and FasL expression and thyrocyte apoptosis using immunohistochemistry and Western blotting. To evaluate the proliferation of thyrocytes, proliferating cell nuclear antigen was examined immunohistochemically. The number of apoptotic cells increased during goiter formation and the early stage of involution, which were also associated with increased number of Fas-positive thyrocytes, and some of these cells contained TUNEL-positive nuclei. However, the expression of FasL was almost constant throughout the experiment. Proliferating cell nuclear antigen/TUNEL ratio markedly increased during goiter formation but decreased particularly during the late stage of goiter involution. Our results indicate that apoptosis of thyrocytes is a main factor of cell loss during goiter formation and involution and suggest that the Fas/FasL system is involved in the induction of apoptosis of these cells. Moreover, the delicate balance between apoptosis and cell proliferation may play an important role in the control of thyroid gland mass.
Animals↗
Cyclic changes in the tension of the contractile vacuole complex membrane control its exocytotic cycle
The freshwater protozoan Paramecium multimicronucleatum maintains a constant cytosolic osmolarity through the exocytotic activity of its contractile vacuole complex. The contractile vacuole (CV) expels the excess cytosolic water, acquired osmotically, to the exterior of the cell at fairly regular intervals. In a single exocytotic cycle, the CV swells as the cytosolic water enters the vacuole, rounds up, and then rapidly shrinks as the fluid is expelled through the pore of the CV. The exocytotic activity of the CV complex can sometimes be slowed and distorted by microelectrode impalement. Using a CV with exocytotic activity slowed in this way makes it possible to determine more precisely the time course of changes in the exocytotic-activity-related membrane capacitance and membrane potential of the organelle. We have clearly demonstrated that the radial arms of the CV were always severed after the CV had exhibited rounding. Microelectrode impalement sometimes caused a failure of the CV pore to open after rounding up, so that the CV entered the next fluid-filling phase without expelling its fluid. The radial arms remained severed from the CV during such prolonged rounding phases and then rejoined the CV at the start of the next fluid-filling phase. The rounding of the CV corresponds to an increase in the tension of the CV membrane. This suggested that the periodic development of increased tension in the CV membrane might be the primary event leading to periodic severing of the radial arms and the opening of the pore. We then observed that the CV and its radial arms sometimes became fragmented into vesicles when the cell had been mechanically ruptured in a salt solution. Many of the resulting in vitro vesicles showed periodic rounding and slackening which occurred at different times so that they were out of phase one with the other. This indicates that the membranes of the CV and the radial arms maintain their ability to develop a periodic increase in tension even after the cell has been ruptured. We propose the hypothesis that the CV membrane (together with its associated cytoskeletal structures) possesses a mechanism by which its tension is periodically increased. Such a periodic change in membrane tension may govern the exocytotic cycle of the contractile vacuole complex by increasing the tension to a point that the radial arms sever from the CV and the pore opens. Conversely, a decrease in the tension causes closure of the pore and rejoining of the radial arms to the CV. Transformation of the CV membrane into 40 nm tubules is assumed to be responsible for the development of tension in the planar CV membrane. The causes of this periodic tubulation must now be sought.
Journal Article↗