Purinergic and mechanical interactions between myo- and secretory epithelial cells in mammary gland.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
K Enomoto
Publications and source records attributed to K Enomoto.
[Magnetization transfer MR of cerebrovascular disorders using calculated images].
This study applied a magnetization transfer contrast method to patients with cerebrovascular disorders. A 1.5T superconducting MR unit was used, and magnetization transfer ratio (MTR) images were calculated by evaluating two paired images before and after off-resonance gradient echo pulse sequences. The normal white matter showed the highest MTRs, CSF the lowest, and gray matter, intermediate. Cerebral ischemic patients showed two patterns according to the chronological stage of the affected area. Lesions in the acute and subacute stages revealed higher transfer rates than those in the chronic stage. Patients with cerebral hemorrhage were divided into three groups: the hyperacute group showed a low transfer pattern; the acute group presented inhomogeneous high transfer rates; and the subacute group showed remarkably low transfer rates. In the acute and subacute ischemic stages, increased macromolecules caused higher MTRs than in the chronic stage. In hemorrhagic groups, low MTRs in subacute hemorrhage reflected the transfer of methemoglobin. High MTRs in acute hemorrhage with rich deoxyhemoglobin suggested increased fibrin, plasma, and serum components of macromolecules. The MTC method provided new chronological information on cerebral hemorrhage, adding to that provided by routine MR images.
Adolescent↗
[New drugs in metastatic breast cancer--1997].
The introduction of new drugs may offer significant hope for improvement in the treatment of breast cancer. They include new cytotoxic agents such as Taxanes, Topoisomerase inhibitor, MDR modulator, new hormone such as 3rd generation nonsteroidal aromatase inhibitor, pure antiestrogen for patients with refractory metastatic breast cancer and new bisphosphonates for those who have metastases to bone. Therefore, some reports evaluating such new drugs were reviewed. Japanese studies revealed response rate of Taxanes in the treatment of metastatic breast cancer as follows; Six out of 22 (27%) with 1 CR for 24 hours infusion, 21 out of 52 (34%) with 2 CR for 3 hours infusion of paclitaxel respectively, 21 out of 31 (41%) with 2 CR for 1 hour infusion, and 32 out of 72 (44%) with 5 CR for 1 hour infusion of Docetaxel, In addition, the MTD of the combination was reached at dose level with 60 mg/sqm of Docetaxel and 400 mg/sqm of cyclophosphamide. As regards hormone therapy, thirty four out of 176 (19%) with 5 CR were observed in phase II study of Fadrozol but results from the phase II study of 3rd generation aromatase inhibitor is not yet accomplished in Japan. However, any european reports did not show a difference in response rate in patients with tamoxifen refractory breast cancer between newer aromatase inhibitor and megasterol, and a good choice of hormones in the treatment of metastatic breast cancer appears to be difficult.
Antineoplastic Agents↗
Bradykinin B2 receptor-induced and inositol tetrakisphosphate-evoked Ca2+ entry is sensitive to a protein tyrosine phosphorylation inhibitor in ras-transformed NIH/3T3 fibroblasts.
Signal transduction from mouse bradykinin B2 receptors to calcium influx was studied in ras-transformed NIH/3T3 (DT) fibroblasts. DT cells were preloaded with fura-2 and whole-cell voltage-clamped. Activation of B2 receptors resulted in a decrease of cellular fluorescence at the excitation wavelength of 340, or 360 nm after MnCl2 application, in both the presence and absence of external Ca2+ in DT cells, at a holding potential of -40 mV. This Mn2+ entry through the Ca2+ influx pathway increased with membrane hyperpolarization. Internal application of inositol 1,3,4,5-tetrakisphosphate (InsP4), but not of inositol 1,4,5-trisphosphate, mimicked membrane potential-dependent Mn2+ entry. Bradykinin- and InsP4-induced Ca2+ influx was blocked by 10-100 microM genistein, a tyrosine kinase inhibitor. B2 receptor activation induced time-dependent tyrosine phosphorylation of mitogen-activated protein kinase and 120 kDa protein, which was dose-dependently inhibited by genistein. Bradykinin was unable to induce Ca2+ oscillations in genistein-treated DT cells. Our results show that bradykinin-induced Ca2+ influx and oscillations depend upon protein tyrosine phosphorylation. The results suggest that two bradykinin B2 receptor-activated signal pathways, protein tyrosine phosphorylation and formation of InsP4, merge at the Ca2+ influx process in ras-transformed NIH/3T3 fibroblasts.
3T3 Cells↗
Cloning and sequencing of the gene encoding the soluble fumarate reductase from Saccharomyces cerevisiae.
A gene of the soluble fumarate reductase (FRDS) that binds FAD non-covalently was cloned by polymerase chain reaction (PCR) using degenerate oligonucleotides designed from partial amino acid sequences of highly purified enzyme. The nucleotide sequence of a 0.99-kb amplified product was found to be nearly identical to a partial sequence of an open reading frame (ORF) previously reported (EMBL database accession number S-30830). According to the sequence in the EMBL database, we cloned 1.7-kb fragment containing entire sequence of this ORF by PCR and found that this fragment contained a perfect match to the 0.99-kb sequence amplified with the degenerate primers. From these results, we concluded that this ORF is the FRDS gene. The amino acid sequences of the regions involved in the non-covalent binding of FAD and the active site, which are conserved among the flavoprotein subunits of membrane-bound fumarate reductase and succinate dehydrogenase, were found in FRDS. However, unlike the membrane-bound enzymes, FRDS did not contain the histidine residue that covalently binds the isoalloxazine ring of FAD at or near the corresponding position. FRDS showed high homology to the product of S. cerevisiae OSM1 gene which was reported to be required for growth in hypertonic media.
Amino Acid Sequence↗
Localization of 7H6 tight junction-associated antigen along the cell border of vascular endothelial cells correlates with paracellular barrier function against ions, large molecules, and cancer cells.
To study the regulation of the endothelial barrier, we examined the relationship between the paracellular barrier function and the expression of 7H6 antigen localized at tight junctions of endothelial cells by using transendothelial electrical resistance (TER), fluxes of albumin and dextran, transmigration of rat mammary cancer (SST-2) cells across rat lung endothelial (RLE) cells, and immunocytochemical expression of 7H6 antigen as parameters. RLE cells cultured at a confluent cell density did not express immunohistochemically demonstrable 7H6 antigen and had low paracellular barrier functions. However, treatment of the endothelial cells with 0.5 mM dibutyryl-cAMP or 10(-6) M all-trans-retinoic acid for 4 days induced 7H6 antigen preferentially at the cell border and simultaneously enhanced the barrier function twofold, in terms of TER and fluxes of albumin and dextran. Furthermore, RA-treated RLE cell monolayers with the enhanced barrier function significantly inhibited the transmigration of SST-2 cells. These results together with those of our previous study indicate that 7H6 antigen has a crucial role in the regulation of paracellular barrier function not only in epithelial cells but also in vascular endothelial cells. The present study also suggests that tight junctions of vascular endothelium in vivo function as a barrier between blood and tissues against metastatic cancer cells.
Animals↗
Effectiveness of an adriamycin immunoconjugate that recognizes the C-erbB-2 product on breast cancer cell lines.
Adriamycin (ADM) was chemically conjugated to a murine monoclonal antibody, A0011, which recognizes the c-erbB-2 product, via a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolane (2-IT). The molar ratio of ADM to the monoclonal antibody ranged from 15:1 to 25:1 and enzyme-linked immunosorbent assay (ELISA) showed that the binding activity of the conjugate was almost retained. We compared the efficacy of A0011 alone, ADM alone, the A0011-ADM conjugate, against the human breast cancer cell lines SK-BR-3, MDA-MB-361, MCF-7, and BT-20. The A0011-ADM conjugate was observed to be ten times more cytotoxic to the cell lines overexpressing the c-erbB-2 product, namely, SK-BR-3 and MDA-MB-361, than free ADM, but it showed weak cytotoxicity against the cell lines with a low level of c-erbB-2 product expression, namely, MCF-7 and BT-20. However, free A0011 and nonspecific murine IgM-ADM conjugate showed no cytotoxicity toward any of the four cell lines, while the addition of a tenfold molar excess of A0011 inhibited conjugate cytotoxicity. These data suggest that conjugate cytotoxicity is antibody-mediated. Moreover, conjugate cytotoxicity at 10(-6)M was correlated with antigen volume, and the data were fitted to the regression equation y = -11.63logX + 116.38 where the correlation coefficient = 0.950. Our results indicate that targeting therapy aiming at the c-erbB-2 product may be useful in the treatment of breast cancers overexpressing the c-erbB-2 product.
Antibiotics, Antineoplastic↗
Alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9-producing gallbladder cancer.
We report a rare case of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9-producing gallbladder cancer with high levels of CA125 and protein induced by vitamin K absence or antagonist II (PIVKA II). A 63-year-old man was diagnosed with gallbladder cancer with metastases to the liver, based on ultrasonography and computed tomography of the abdomen showing multiple tumorous lesions in the liver and a thickened gallbladder wall. Laboratory data showed high levels of tumor markers: 4647.4 ng/ml AFP, 9987.1 ng/ml CEA, 11,704.0 U/ml CA19-9, 847.6 U/ml CA125, and 0.2 AU/ ml PIVKA II. AFP in the present case showed an increase in Concanavalin A-nonbinding fraction and an increase in Lens culinaris lectin-binding fraction by affinity column chromatography. The patient died of hepatic failure. Autopsy revealed gallbladder cancer consisting of papillary adenocarcinoma and moderately differentiated tubular adenocarcinoma. By immunohistochemical staining, AFP was detected in the papillary adenocarcinoma portion of the primary focus and metastatic tumor cells in the liver, but was not detected in noncancerous liver tissue. CEA and CA19-9 were detected mainly in the tubular adenocarcinoma portion.
Antigens, Tumor-Associated, Carbohydrate↗
Epidermal growth factor receptor-dependent cytotoxic effect by an EGF-ribonuclease conjugate on human cancer cell lines--a trial for less immunogenic chimeric toxin.
Mammalian pancreatic ribonuclease (RNase) was conjugated chemically via a disulfide bond to human or murine epidermal growth factor (EGF). The conjugation between EGF and RNase was ascertained by SDS-PAGE using reduced and nonreduced conjugates. The EGF-RNase conjugate retained potent RNase activity and competed with 125I-EGF for binding to EGFR to the same extent as unconjugated EGF. Both the human and murine EGF-RNase conjugates showed dose-dependent cytotoxicity against EGFR-overexpressing A431 human squamous carcinoma cells with IC50 values of 3 x 10(-7) M and 6 x 10(-7) M, respectively, whereas free RNase had an IC50 of 10(-4) M. Against the EGFR-deficient small-cell lung cancer cell line H69, the EGF-RNase conjugate had no cytotoxic effect. The Human EGF-RNase conjugate showed dose-dependent cytotoxicity against other squamous carcinoma cell lines (TE-5, TE-1) and breast cancer cell lines (BT-20, SK-BR-3, MCF-7) and the cytotoxicity of the conjugate correlated positively with the level of expression of EGFR by each cell line. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone on any cell line. Excess free EGF blocked EGF-RNase conjugate cytotoxicity against A431 cells. These results suggest that the EGF-RNase conjugate may be a more effective anticancer agent with less immunogenicity than coventional chimeric toxins.
Antineoplastic Agents↗
Epidermal growth factor receptor-dependent cytotoxicity for human squamous carcinoma cell lines of a conjugate composed of human EGF and RNase 1.
Recombinant human ribonuclease 1 (RNase 1) was chemically linked to recombinant human epidermal growth factor (EGF). The EGF-RNase conjugate showed dose-dependent cytotoxicity for EGF receptor-overexpressing A431 and TE-8 human squamous carcinoma cells with an IC50 of 2 x 10(-7)M and 10(-6)M, respectively, whereas the IC50 of RNase alone was almost 10(-4)M. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone. The conjugate showed no detectable cytotoxicity against EGF receptor-deficient small cell lung cancer cells (H69). Addition of excess EGF in the medium protected A431 cells from the EGF-RNase conjugate cytotoxicity. The cytotoxicity of the EGF-RNase conjugate was positively correlated with the EGF receptor numbers of each cell line. The chimeric toxin composed of only human proteins might be a more useful anti-cancer agent with less immunogenicity than the conventional chimeric toxins.
Carcinoma, Squamous Cell↗
Spinal giant intradural perimedullary arteriovenous fistula: clinical and neuroradiological study in one case with review of literature.
BACKGROUND: Giant intradural perimedullary arteriovenous fistula with massive spinal cord compression is rare. The therapeutic difficulties include whether endovascular embolization or direct surgical excision should be selected. We present a patient with the largest giant spinal intradural perimedullary arteriovenous fistula shown by magnetic resonance imaging so far reported, who was successfully treated by a combination of endovascular embolization and direct surgery. CASE DESCRIPTION: A 16-year-old girl presented with a giant intradural arteriovenous fistula (perimedullary Type II) at the C4-5 level, manifesting as progressive cervical myeloradiculopathy. The single-hole fistula was supplied by the anterior spinal artery and an ascending artery arising from both the costocervical and highest intercostal arteries with a rapid transit time, and drained superiorly to the foramen magnum, and inferiorly to the thoracic spinal canal, through a huge venous lake at the site of the arteriovenous connection. The patient was treated by transarterial embolization with platinum coils and silk, followed by surgical excision with excellent results at 12 months' follow-up. CONCLUSIONS: We recommend that such a huge perimedullary arteriovenous fistula with a rapid transit time, and severe cord and root compression, should be treated with embolization followed by surgical excision.
Adolescent↗
Translocation (3;14)(q27;q11): a new variant translocation in a patient with non-Hodgkin's lymphoma of B-cell type with BCL6 rearrangement.
We report a 65-year-old woman with non-Hodgkin's lymphoma (NHL) carrying a t(3;14)(q27;q11) and BCL6 rearrangement in the affected cells. She had generalized lymphadenopathy and the bone marrow was infiltrated by lymphoma cells at presentation. Histological diagnosis was "malignant lymphoma, diffuse, large cell" type according to an International Working Formulation. Chromosome analysis revealed a t(3;14)(q27;q11), which is a new variant translocation of t(3;14) (q27;q32). Southern blot analysis showed rearrangement of BCL6, JH, and TCR beta but not of TCR delta. Cosmid probe of BCL6 hybridized to 14q11 and 3q27 by fluorescence in situ hybridization (FISH). Although the band 14q11 is a locus of T-cell receptor alpha- and delta-chains (TCR alpha/delta), lymphoma cells expressed B-cell, IgGk phenotype. The findings suggest that a novel proto-oncogene in the vicinity of TCR alpha/delta is involved in this translocation.
Aged↗
Therapeutic efficacy of pamidronate in combination with chemotherapy to bone metastasis of breast cancer in a rat model.
Bone metastasis is clinically often recognized in breast cancer patients, and in the progression of bone destruction due to bone metastasis, osteoclastic bone resorption is an important step. Therefore, drugs such as bisphosphonates-which have anti-osteoclastic activity-are expected to inhibit the progression of bone metastasis. However, bisphosphonates demonstrate no cytotoxic effects for cancer cells. In the present study we have evaluated the therapeutic efficacy of pamidronate (3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid) combined with mitomycin C (MMC) on bone metastasis of breast cancer using an animal model. The model for bone metastasis was developed by injecting c-SST-2 (spontaneously developed rat mammary adenocarcinoma in a SHR rat) cells into the thoracic aorta of 45-46 day-old female SHR rats. Three weeks after the tumour cell injection, these 48 animals were divided into four groups: control, n = 16; pamidronate, n = 12; MMC, n = 10; pamidronate with MMC, n = 10). In order to evaluate therapeutic effects on bone metastasis in each animal, the whole spine was harvested for histological examination. The bone metabolic markers used were: pyridinoline/creatinine (Pyd/Cr), deoxypyridinoline/creatinine (Dpd/Cr), bone alkaline phosphatase (BAP), and osteocalcin-measured 1 week after therapy. Histological scores of bone destruction in the treatment groups were lower than those of the control, and there were no differences among treatment groups. Although the values of Pyd/Cr and Dpd/Cr in the treatment groups, including pamidronate, were significantly lower than those in the control (P < 0.05), the other markers did not differ. It was suggested that pamidronate inhibited the progression of bone resorption, mainly by osteoclast activation due to bone metastasis, and Pyd/Cr and Dpd/Cr could be useful in part as a marker which reflects therapeutic effect. However, no additional effects were observed when it was combined with MMC.
Animals↗
Hepatocellular carcinoma induction in LEC rats by a low dose of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.
A food-borne heterocyclic amine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), induces hepatocellular carcinomas (HCCs) in F344 male rats at an incidence of 95%, when fed in the diet at 400 ppm for 61 weeks. In this study, the effect of a low dose of MeIQx was examined in Long-Evans with cinnamon-like coat color (LEC) rats, which have a mutation in Atp7b and suffer from hereditary hepatitis and HCCs, with high levels of copper accumulation in the liver. Rats of the LEC and Long-Evans with agouti coat color (LEA) sibling lines were given a diet containing 40 ppm MeIQx from the age of 23 weeks to 63 weeks, for a total administration period of 40 weeks. In LEC rats, HCCs were observed in 8/8 animals administered MeIQx, and 2/8 rats receiving a normal diet. The number of HCCs per rat (mean +/- SD) was 2.8 +/- 2.0 and 0.3 +/- 0.5, respectively. In the LEA rats, however, no tumors were induced by administration of MeIQx. These results indicate that damaged liver associated with compensatory cell proliferation is much more susceptible to chemical hepatocarcinogens, including MeIQx, than the normal liver.
Alanine Transaminase↗
Choriocarcinoma in infant and mother: a case report.
We present a case of gestational choriocarcinoma that developed in a pregnant woman with metastases to her baby. In this case, severe anemia and hepatomegaly of the baby were noticed after delivery. Despite intensive treatments, the tumor progressed rapidly, and the baby died at the age of 38 days. Accurate diagnosis was made after autopsy. When the baby's mother visited our hospital again at 4 months postpartum, there were widespread multiple metastases to her lungs and liver. We want to emphasize that if a neonate or infant has anemia and/or hepatomegaly, it is necessary to be aware of the possibility of infantile choriocarcinoma with the presence of an occult tumor in the mother and to examine the mother's and infant's hCG levels immediately.
Adult↗
Forskolin derivatives. I. Synthesis, and cardiovascular and adenylate cyclase-stimulating activities of water-soluble forskolins.
Water-soluble forskolin and 7-deacetylforskolin derivatives with an aminoacetyl, a 3-aminopropionyl, or a 4-aminobutyryl group at the 6- or 7-position were prepared, and their positive inotropic as well as vasodilative activities were evaluated in anesthetized dogs. 7-Deacetylforskolin (2) and 7-deacetyl-1-silylforskolin (6) were converted to the corresponding 7-chloroacylderivatives (3, 7, 10), which were reacted with amines to obtain 7-aminoacyl-7-deacetylforskolins (4a-f, 9a, b, 11). The 7-acyl substituents migrated to the 6-position with sodium hydroxide in acetonitrile-water to afford 6-aminoacyl-7-deacetylforskolins (12a-f). The 7-position of 12a, d-f was selectively acetylated with acetyl chloride to obtain the corresponding 6-aminoacylforskolins (13a-d). Among the 6-aminoacylforskolins, 6-(3-dimethylaminopropionyl)forskolin (13b) and 6-(4-dimethylaminobutyryl)forskolin (13d) exhibited potent positive inotropic and vasodilative activities comparable to those of forskolin (1). The activities of 13b and 13d were approximately ten times more potent than those of 7-aminoacyl- and 6-aminoacyl-7-deacetylforskolins (4a-f, 9a, 12a-c, f). 6-Dimethylaminoacetylforskolin (13a) and 6-(3-diethylaminopropionyl)forskolin (13c) were less potent than 1. The effects of the soluble forskolins on adenylate cyclase activity were also examined in vitro. 6-Aminoacylforskolins (13a-d) exhibited potent adenylate cyclase-stimulating activity, comparable to that of 1.
Adenylyl Cyclases↗
[Introduction of an improved face simulation system].
Explore the source record for details and available documents.
Adolescent↗
A feasibility study on L-[1-carbon-11]tyrosine and L-[methyl-carbon-11]methionine to assess liver protein synthesis by PET.
UNLABELLED: We studied the potential of L-[1-11C]tyrosine ([1-11C]Tyr) and L-[methyl-11C]methionine ([Me-11C]Met) as tracers for measuring protein synthesis rate (PSR) in the liver by PET and proposed their metabolic models. METHODS: In the liver and plasma of control and cycloheximide-treated mice injected with [1-14C]Tyr and [Me-3H]Met, incorporation of the radioactivity into the acid-soluble fraction and chloroform/methanol-extract (CM), RNA and protein fractions were measured. Data were compared with those from rat studies with 11C-labeled analogs and PET. RESULTS: In mice, liver uptake of [Me-3H]Met was over twice as large as that of [1-14C]Tyr. Similar uptake patterns of the 11C-labeled analogs were found in rats by PET. In the mouse liver at 1 to 6 hr after injection, approximately 69%-73% of the 14C was detected in the protein fraction, whereas approximately 65%-70% of the 3H was in the CM fraction, which reflected phospholipid synthesis. In plasma, the percentages of the protein fractions were approximately 73%-76% for 14C and approximately 36%-46% for 3H. Gel-filtration analysis suggested that 80% of the 14C-labeled plasma proteins was albumin originating from the liver, which corresponds to approximately 25% of the total labeled proteins synthesized in the liver at 6 hr. When protein synthesis was inhibited by cycloheximide, the liver uptake of the [1-14C]Tyr and the protein-incorporation of 14C in the liver and in plasma were decreased dose-dependently. On the other hand, uptake of [Me-3H]Met was significantly enhanced in the liver due to increased incorporation into the CM fraction. CONCLUSION: [1-Carbon-11]Tyr can be used for measuring the PSR in the liver by PET. Liver uptake of [Me-11C]Met mainly reflects phospholipid synthesis through the transmethylation process.
Animals↗