Novel Cell Nucleus Directed Fluorescent Tetraazacyclododecane-Tetraacetic Acid Compounds

2009 ◽  
Vol 5 (1) ◽  
pp. 93-102 ◽  
Author(s):  
A. Sturzu ◽  
U. Klose ◽  
H. Echner ◽  
M. Regenbogen ◽  
H. Kalbacher ◽  
...  
Keyword(s):  
Cell Nucleus ◽  
Tetraacetic Acid ◽  
Tetraazacyclododecane Tetraacetic Acid

scholarly journals Evaluation of Radiolabeled Girentuximab In Vitro and In Vivo

2018 ◽  
Vol 11 (4) ◽  
pp. 132 ◽  
Author(s):  
Tais Basaco ◽  
Stefanie Pektor ◽  
Josue Bermudez ◽  
Niurka Meneses ◽  
Manfred Heller ◽  
...  
Keyword(s):  
Specific Binding ◽  
Sodium Ascorbate ◽  
Tumor Uptake ◽  
Tetraacetic Acid ◽  
In Vivo Experiments ◽  
Caix Expression ◽  
Tetraazacyclododecane Tetraacetic Acid

Girentuximab (cG250) targets carbonic anhydrase IX (CAIX), a protein which is expressed on the surface of most renal cancer cells (RCCs). cG250 labeled with 177Lu has been used in clinical trials for radioimmunotherapy (RIT) of RCCs. In this work, an extensive characterization of the immunoconjugates allowed optimization of the labeling conditions with 177Lu while maintaining immunoreactivity of cG250, which was then investigated in in vitro and in vivo experiments. cG250 was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA(SCN)) by using incubation times between 30 and 90 min and characterized by mass spectrometry. Immunoconjugates with five to ten DOTA(SCN) molecules per cG250 molecule were obtained. Conjugates with ratios less than six DOTA(SCN)/cG250 had higher in vitro antigen affinity, both pre- and postlabeling with 177Lu. Radiochemical stability increased, in the presence of sodium ascorbate, which prevents radiolysis. The immunoreactivity of the radiolabeled cG250 tested by specific binding to SK-RC-52 cells decreased when the DOTA content per conjugate increased. The in vivo tumor uptake was < 10% ID/g and independent of the total amount of protein in the range between 5 and 100 µg cG250 per animal. Low tumor uptake was found to be due to significant necrotic areas and heterogeneous CAIX expression. In addition, low vascularity indicated relatively poor accessibility of the CAIX target.

Cohort Study of Somatostatin-Based Radiopeptide Therapy With [90Y-DOTA]-TOC Versus [90Y-DOTA]-TOC Plus [177Lu-DOTA]-TOC in Neuroendocrine Cancers

2012 ◽  
Vol 30 (10) ◽  
pp. 1100-1106 ◽  
Author(s):  
Linda Villard ◽  
Anna Romer ◽  
Nicolas Marincek ◽  
Philippe Brunner ◽  
Michael T. Koller ◽  
...  
Keyword(s):  
Cohort Study ◽  
Current Practice ◽  
Cox Regression ◽  
Renal Toxicity ◽  
Tetraacetic Acid ◽  
Neuroendocrine Cancer ◽  
Radiopeptide Therapy ◽  
Tetraazacyclododecane Tetraacetic Acid ◽  
Neuroendocrine Cancers ◽  
Single Versus

Purpose Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes. Patients and Methods In a cohort study, patients with metastasized neuroendocrine cancer were treated with repeated cycles of 90yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([90Y-DOTA]-TOC) or with cycles alternating between [90Y-DOTA]-TOC and 177lutetium-labeled DOTA-TOC ([177Lu-DOTA]-TOC) until tumor progression or permanent toxicity. Multivariable Cox regression and competing risk regression were used to study predictors of survival and renal toxicity in patients completing three or more treatment cycles. Results A total of 486 patients completed three or more treatment cycles; 237 patients received [90Y-DOTA]-TOC and 249 patients received [90Y-DOTA]-TOC + [177Lu-DOTA]-TOC. Patients receiving [90Y-DOTA]-TOC + [177Lu-DOTA]-TOC had a significantly longer survival than patients receiving [90Y-DOTA]-TOC alone (5.51 v 3.96 years; hazard ratio, 0.64; 95% CI, 0.47 to 0.88; P = .006). The rates of severe hematologic toxicities (6.3% v 4.4%; P = .25) and severe renal toxicity (8.9% v 11.2%; P = .47) were comparable in both groups. Conclusion [90Y-DOTA]-TOC + [177Lu-DOTA]-TOC was associated with improved overall survival compared with [90Y-DOTA]-TOC alone in patients completing three or more cycles of treatment. Contrary to the current practice in radiopeptide therapy, our results suggest an advantage of using a combination of radioisotopes.

Organization of transcription and pre-mRNA splicing within the mammalian cell nucleus

1995 ◽  
Vol 53 ◽  
pp. 768-769
Author(s):  
D.L. Spector ◽  
S. Huang ◽  
S. Kaurin
Keyword(s):  
Rna Polymerase Ii ◽  
Cell Nucleus ◽  
Functional Organization ◽  
Mrna Splicing ◽  
Splicing Factors ◽  
Interchromatin Granule Clusters ◽  
Interchromatin Granule ◽  
Nuclear Regions ◽  
Relationship Of ◽  
Perichromatin Fibrils

We have been interested in the organization of RNA polymerase II transcription and pre-mRNA splicing within the cell nucleus. Several models have been proposed for the functional organization of RNA within the eukaryotic nucleus and for the relationship of this organization to the distribution of pre-mRNA splicing factors. One model suggests that RNAs which must be spliced are capable of recruiting splicing factors to the sites of transcription from storage and/or reassembly sites. When one examines the organization of splicing factors in the nucleus in comparison to the sites of chromatin it is clear that splicing factors are not localized in coincidence with heterochromatin (Fig. 1). Instead, they are distributed in a speckled pattern which is composed of both perichromatin fibrils and interchromatin granule clusters. The perichromatin fibrils are distributed on the periphery of heterochromatin and on the periphery of interchromatin granule clusters as well as being diffusely distributed throughout the nucleoplasm. These nuclear regions have been previously shown to represent initial sites of incorporation of 3H-uridine.

Immunolocalization of nuclear antigens in cryofixed cells which have been prepared by molecular distillation drying or freeze-substitution

1990 ◽  
Vol 48 (3) ◽  
pp. 898-899
Author(s):  
David L. Spector ◽  
Robert J. Derby
Keyword(s):  
Cell Nucleus ◽  
Molecular Distillation ◽  
Functional Organization ◽  
Freeze Substitution ◽  
3 Dimensional ◽  
Small Nuclear Ribonucleoprotein ◽  
Nuclear Antigens ◽  
Dimensional Reconstruction ◽  
Nuclear Regions ◽  
Immunoperoxidase Labeling

Studies in our laboratory are involved in evaluating the structural and functional organization of the mammalian cell nucleus. Since several major classes (U1, U2, U4/U6, U5) of small nuclear ribonucleoprotein particles (snRNPs) play a crucial role in the processing of pre-mRNA molecules, we have been interested in the localization of these particles within the cell nucleus. Using pre-embedding immunoperoxidase labeling combined with 3-dimensional reconstruction, we have recently shown that nuclear regions enriched in snRNPs form a reticular network within the nucleoplasm which extends between the nucleolar surface and the nuclear envelope. In the present study we were inte rested in extending these nuclear localizations using cell preparation techniques which avoid slow penetration of fixatives, chemical crosslinking of potential antigens and solvent extraction. CHOC 400 cells were cryofixed using a CF 100 ultra rapid cooling device (LifeCell Corp.). After cryofixation cells were molecular distillation dried, vapor osmicated, in filtra ted in 100% Spurr resin in vacuo and polymerized in molds a t 60°C. Using this procedure we were able to evaluate the distribution of snRNPs in resin embedded cells which had not been chemically fixed, incubated in cryoprotectants or extracted with solvents.

Heterozygous Abnormal Fibrinogen Osaka III with the Replacement of γ Arginine-275 by Histidine Has an Apparently Higher Molecular Weight γ-Chain Variant

1992 ◽  
Vol 68 (05) ◽  
pp. 534-538 ◽  
Author(s):  
Nobuhiko Yoshida ◽  
Shingi Imaoka ◽  
Hajime Hirata ◽  
Michio Matsuda ◽  
Shinji Asakura
Keyword(s):  
Molecular Weight ◽  
Sodium Dodecyl Sulfate ◽  
Gel Electrophoresis ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Tetraacetic Acid ◽  
Fibrin Monomer ◽  
Sds Page ◽  
Thrombotic Tendency ◽  
Chain Variant

SummaryCongenitally abnormal fibrinogen Osaka III with the replacement of γ Arg-275 by His was found in a 38-year-old female with no bleeding or thrombotic tendency. Release of fibrinopeptide(s) by thrombin or reptilase was normal, but her thrombin or reptilase time in the absence of calcium was markedly prolonged and the polymerization of preformed fibrin monomer which was prepared by the treatment of fibrinogen with thrombin or reptilase was also markedly defective. Propositus' fibrinogen had normal crosslinking abilities of α- and γ-chains. Analysis of fibrinogen chains on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the system of Laemmli only revealed the presence of abnormal γ-chain with an apparently higher molecular weight, the presence of which was more clearly detected with SDS-PAGE of fibrin monomer obtained by thrombin treatment. Purified fragment D1 of fibrinogen Osaka III also seemed to contain an apparently higher molecular weight fragment D1 γ remnant on Laemmli gels, which was digested faster than the normal control by plasmin in the presence of [ethy-lenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA).

Super-Resolution Microscopy in Studying the Structure and Function of the Cell Nucleus

Acta Naturae ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 42-51
Author(s):  
S. S. Ryabichko ◽  
◽  
A. N. Ibragimov ◽  
L. A. Lebedeva ◽  
E. N. Kozlov ◽  
...  
Keyword(s):  
Cell Nucleus ◽  
Super Resolution ◽  
Structure And Function ◽  
And Function ◽  
Super Resolution Microscopy

Expression of Ki-67 has Correlation with the Degree and Size of Endometriosis Cysts

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Ruswana Anwar ◽  
Muhammad Alif ◽  
Adhi Pribadi
Keyword(s):  
Laparoscopic Surgery ◽  
Cell Nucleus ◽  
Significant Relationship ◽  
Strong Relationship ◽  
Cyst Size ◽  
Ki 67 ◽  
Cut Method ◽  
Close Relationship ◽  
Dividing Cells ◽  
Aggressive Tumor

Endometriosis is one of the most common gynecological problem. Cells resulted in chronic inflammation and progressive, proliferative, invasive and even infiltrating an area that resembles the character of the malignancy. Ki-67 is an antigen on the cell nucleus that is found only in actively dividing cells. Expression of Ki-67 are associated with an aggressive tumor and metastasis. This study aims to determine the level of Ki-67 expression correlation with stage and size of the endometriosis cyst. Methods research is observational analytic cross cut method on 56 paraffin blocks of patients who have been diagnosed with endometriosis and had performed a laparotomy or laparoscopic surgery in Dr Hasan Sadikin Hospital. The results showed a significant relationship between the level of expression of Ki-67 with endometriosis cyst size (p <0.001) with a fairly strong relationship (0.55) according to statistics based on criteria Guilford. Moreover the results also showed a significant relationship between the level of expression of Ki-67 with endometriosis stage (p <0.001) with a fairly close relationship (0.564) according to statistics based on criteria Guilford. It can be concluded that the expression of Ki-67 associated with cyst size and stage of endometriosis. Keywords: Ki-67, endometriosis stage, endometriosis cyst

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