Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
1.
Clin. transl. oncol. (Print) ; 20(6): 713-718, jun. 2018. ilus, tab, graf
Article in English | IBECS | ID: ibc-173619

ABSTRACT

Introduction: Hematologic toxicity (HT) in cervical cancer patients can cause treatment delays and reduction in chemotherapy, especially in high risk patients. Dose to PET-defined regions of active bone marrow (ABM) has been shown to correlate with cytopenias. An absolute volume of ABM spared may accurately represent hematopoietic reserve and risk of HT. This analysis evaluates whether the volume of ABM spared can more accurately predict HT compared to conventional dosimetric parameters. Methods: Thirty-one patients treated for cervical cancer with chemoradiation from 9/2011 to 8/2016 were retrospectively reviewed. Receiver operating characteristic (ROC) curve were used to assess optimal cutpoint criterions for grade 3+ HT based on the CTCAEv4. Conventional dosimetric parameters to PBM and ABM (mean dose, V10, V20, V40) were assessed as well as the absolute volume (cc) of PBM and ABM spared 10, 20, and 40 Gy. Results: The absolute volume of PBM spared 10 Gy (< 230 cc; AUC 0.732, p = 0.03) as well as volume of ABM spared 10 Gy (< 179 cc; AUC 0.815, p = 0.0002), spared 20 Gy (< 186 cc; AUC 0.774, p = 0.0015), and spared 40 Gy (< 738 cc; AUC 0.887, p < 0.0001) all predicted grade 3+ HT. In patients with < 738 cc of ABM spared 40 Gy, 18/18 (100%) had grade 3+ toxicity compared to 6/13 (46%) of patients with > 738 cc of ABM spared 40 Gy (p < 0.0001). Conclusion: The baseline volume of ABM and the fraction of ABM present in patients vary significantly. The ongoing NRG-GY006 trial and other efforts at bone marrow sparing use V10, V20, and mean dose to the ABM during planning optimization. This analysis suggests that the volume of ABM spared 40 Gy (> 738 cc) may be a stronger predictor of HT than conventional dosimetric parameters. This should be further evaluated for clinical use


No disponible


Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Positron Emission Tomography Computed Tomography/methods , Uterine Cervical Neoplasms/therapy , Chemoradiotherapy/adverse effects , Toxicity Tests/methods , Radioisotopes/administration & dosage , Uterine Cervical Neoplasms/pathology , Bone Marrow , Bone Marrow/radiation effects , Retrospective Studies
2.
Clin Transl Oncol ; 20(6): 713-718, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29076030

ABSTRACT

INTRODUCTION: Hematologic toxicity (HT) in cervical cancer patients can cause treatment delays and reduction in chemotherapy, especially in high risk patients. Dose to PET-defined regions of active bone marrow (ABM) has been shown to correlate with cytopenias. An absolute volume of ABM spared may accurately represent hematopoietic reserve and risk of HT. This analysis evaluates whether the volume of ABM spared can more accurately predict HT compared to conventional dosimetric parameters. METHODS: Thirty-one patients treated for cervical cancer with chemoradiation from 9/2011 to 8/2016 were retrospectively reviewed. Receiver operating characteristic (ROC) curve were used to assess optimal cutpoint criterions for grade 3+ HT based on the CTCAEv4. Conventional dosimetric parameters to PBM and ABM (mean dose, V10, V20, V40) were assessed as well as the absolute volume (cc) of PBM and ABM spared 10, 20, and 40 Gy. RESULTS: The absolute volume of PBM spared 10 Gy (< 230 cc; AUC 0.732, p = 0.03) as well as volume of ABM spared 10 Gy (< 179 cc; AUC 0.815, p = 0.0002), spared 20 Gy (< 186 cc; AUC 0.774, p = 0.0015), and spared 40 Gy (< 738 cc; AUC 0.887, p < 0.0001) all predicted grade 3+ HT. In patients with < 738 cc of ABM spared 40 Gy, 18/18 (100%) had grade 3+ toxicity compared to 6/13 (46%) of patients with > 738 cc of ABM spared 40 Gy (p < 0.0001). CONCLUSION: The baseline volume of ABM and the fraction of ABM present in patients vary significantly. The ongoing NRG-GY006 trial and other efforts at bone marrow sparing use V10, V20, and mean dose to the ABM during planning optimization. This analysis suggests that the volume of ABM spared 40 Gy (> 738 cc) may be a stronger predictor of HT than conventional dosimetric parameters. This should be further evaluated for clinical use.


Subject(s)
Bone Marrow/pathology , Chemoradiotherapy/adverse effects , Hematologic Diseases/diagnosis , Positron-Emission Tomography/methods , Uterine Cervical Neoplasms/therapy , Adult , Aged , Bone Marrow/diagnostic imaging , Bone Marrow/drug effects , Bone Marrow/radiation effects , Female , Follow-Up Studies , Hematologic Diseases/diagnostic imaging , Hematologic Diseases/etiology , Humans , Middle Aged , Prognosis , Retrospective Studies , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/pathology
3.
Biomater Sci ; 5(4): 707-717, 2017 Mar 28.
Article in English | MEDLINE | ID: mdl-28184390

ABSTRACT

PEGylated gold nanoparticles (AuNPs) have an extended circulation time after intravenous injection in vivo and exhibit favorable properties for biosensing, diagnostic imaging, and cancer treatment. No impact of PEGylated AuNPs on the barrier forming properties of endothelial cells (ECs) has been reported, but recent studies demonstrated that unexpected effects on erythrocytes are observed. Almost all studies to date have been with static-cultured ECs. Herein, ECs maintained under physiological cyclic stretch and flow conditions and used to generate a blood-brain barrier model were exposed to 20 nm PEGylated AuNPs. An evaluation of toxic effects, cell stress, the release profile of pro-inflammatory cytokines, and blood-brain barrier properties showed that even under physiological conditions no obvious effects of PEGylated AuNPs on ECs were observed. These findings suggest that 20 nm-sized, PEGylated AuNPs may be a useful tool for biomedical applications, as they do not affect the normal function of healthy ECs after entering the blood stream.


Subject(s)
Endothelial Cells/drug effects , Gold/metabolism , Nanoparticles/metabolism , Polyethylene Glycols/metabolism , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/pathology , Cells, Cultured , Endothelial Cells/metabolism , Endothelial Cells/pathology , Gold/chemistry , Gold/toxicity , Human Umbilical Vein Endothelial Cells , Humans , Nanoparticles/chemistry , Nanoparticles/toxicity , Particle Size , Polyethylene Glycols/chemistry , Polyethylene Glycols/toxicity , Swine
4.
Am J Physiol Heart Circ Physiol ; 302(10): H1998-2007, 2012 May 15.
Article in English | MEDLINE | ID: mdl-22427515

ABSTRACT

The cAMP response element binding protein (CREB) belongs to the CREB/cAMP response element binding modulator/activating transcription factor 1 family of cAMP-dependent transcription factors mediating a regulation of gene transcription in response to cAMP. Chronic stimulation of ß-adrenergic receptors and the cAMP-dependent signal transduction pathway by elevated plasma catecholamines play a central role in the pathogenesis of heart failure. Ion channel remodeling, particularly a decreased transient outward current (I(to)), and subsequent action potential (AP) prolongation are hallmarks of the failing heart. Here, we studied the role of CREB for ion channel regulation in mice with a cardiomyocyte-specific knockout of CREB (CREB KO). APs of CREB KO cardiomyocytes were prolonged with increased AP duration at 50 and 70% repolarization and accompanied by a by 51% reduction of I(to) peak amplitude as detected in voltage-clamp measurements. We observed a 29% reduction of Kcnd2/Kv4.2 mRNA in CREB KO cardiomyocytes mice while the other I(to)-related channel subunits Kv4.3 and KChIP2 were not different between groups. Accordingly, Kv4.2 protein was reduced by 37% in CREB KO. However, we were not able to detect a direct regulation of Kv4.2 by CREB. The I(to)-dependent AP prolongation went along with an increase of I(Na) and a decrease of I(Ca,L) associated with an upregulation of Scn8a/Nav1.6 and downregulation of Cacna1c/Cav1.2 mRNA in CREB KO cardiomyocytes. Our results from mice with cardiomyocyte-specific inactivation of CREB definitively indicate that CREB critically regulates the AP shape and duration in the mouse ventricle, which might have an impact on ion channel remodeling in situations of altered cAMP-dependent signaling like heart failure.


Subject(s)
Action Potentials/physiology , Cyclic AMP Response Element-Binding Protein/physiology , Heart Ventricles/cytology , Ion Channels/physiology , Myocytes, Cardiac/physiology , Ventricular Function/physiology , Animals , Calcium Channels, L-Type/physiology , Cyclic AMP Response Element-Binding Protein/deficiency , Cyclic AMP Response Element-Binding Protein/genetics , Down-Regulation/physiology , Mice , Mice, Knockout , Models, Animal , Myocytes, Cardiac/cytology , NAV1.6 Voltage-Gated Sodium Channel , Nerve Tissue Proteins/physiology , Patch-Clamp Techniques , Signal Transduction/physiology , Sodium Channels/physiology , Up-Regulation/physiology
5.
Zentralbl Gynakol ; 110(12): 784-7, 1988.
Article in German | MEDLINE | ID: mdl-2975121

ABSTRACT

It is reported about a first successful program of gamete intra fallopian transfer (GIFT) as a supplement to intrauterine insemination and to in vitro fertilization (IVF). In 29 patients after HMG stimulation of the ovaries and laparoscopic aspiration of follicles recovered oocytes have been introduced together with prepared sperm via a special catheter directly into the ampulla of the oviduct. In 21 patients with different causes of infertility optimal stimulation conditions could be achieved. A pregnancy rate of 41.4% is the result of 29 GIFT events and 3 of them resulted in spontaneous term deliveries (10.3%).


Subject(s)
Infertility, Female/therapy , Insemination, Artificial, Homologous/methods , Insemination, Artificial/methods , Adult , Fallopian Tubes , Female , Humans , Laparoscopy , Pregnancy , Prognosis
SELECTION OF CITATIONS
SEARCH DETAIL
...