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1.
AJR Am J Roentgenol ; 216(4): 1040-1045, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33566634

RESUMEN

OBJECTIVE. We hypothesized that intravitreal silicone oil would show attenuation similar to that of fat on dual-energy CT 190-keV virtual monoenergetic images (VMIs) with high frequency and that this appearance would enable confident determination of the presence or absence of intravitreal silicone oil. The purpose of the present study was to test our hypothesis in a blinded multireader study of selected patients with and without intravitreal silicone oil as well as in an unblinded ROI-based assessment. MATERIALS AND METHODS. In this retrospective study of 50 dual-energy CT examinations of the head that included 100 globes (64 that were normal, 19 that exhibited hyperattenuating mimics, and 17 that contained silicone oil), three neuroradiologists independently assessed anonymized 190-keV VMIs for intravitreal attenuation similar to that of fat. Interobserver agreement was calculated. The mean attenuation value on weighted-average images and 190-keV VMIs was recorded. RESULTS. The three readers identified intravitreal attenuation values similar to that of fat in 100% of globes that contained silicone oil and 0% of globes that did not contain silicone oil (100% sensitivity, specificity, PPV, and accuracy) with 100% agreement. The mean attenuation value of silicone oil on 190-keV VMIs was -55 HU, which was significantly less than the mean attenuation on 190-keV VMIs of normal globes and hyperattenuating mimics (p < .001 for both). CONCLUSION. Intravitreal silicone oil shows attenuation of -60 to -49 HU on 190-keV VMIs. With the use of these images only, three neuroradiologists identified intravitreal silicone oil with 100% accuracy and perfect agreement.


Asunto(s)
Aceites de Silicona , Tomografía Computarizada por Rayos X/métodos , Cuerpo Vítreo/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto Joven
2.
J Comput Assist Tomogr ; 45(1): 142-145, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33186176

RESUMEN

OBJECTIVE: The objective of this study is to establish the prevalence of internal auditory canal diverticula spanning all age groups imaged for reasons other than hearing loss and to investigate changes in prevalence with age to determine if it is a finding that develops over time. METHODS: We retrospectively evaluated 1000 cervical spine computed tomographies obtained in patients age 0-99 years for presence of internal auditory canal diverticula. RESULTS: A total of 405 patients (208 men; 197 women) were included. Internal auditory canal diverticula were identified in 23 patients (5.7%). No statistically significant association between internal auditory canal diverticula and patient age was found (P = 0.68). CONCLUSIONS: The prevalence of internal auditory canal diverticula on cervical spine computed tomographies is 5.7%. No change in prevalence was observed with increasing age supporting the hypothesis that internal auditory canal diverticula represent a normal anatomic variant rather than acquired pathology.


Asunto(s)
Vértebras Cervicales/diagnóstico por imagen , Enfermedades del Oído/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Adulto Joven
3.
J Comput Assist Tomogr ; 44(3): 370-373, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31929379

RESUMEN

Silicone oil is used as an intravitreal injection to treat retinal detachment. This material can spread into the subarachnoid space, where it may be mistaken for acute hemorrhage on single-energy computed tomography. This report describes the appearance of intravitreal silicone oil on dual-energy computed tomography, emphasizing unique virtual monoenergetic imaging characteristics that allow for confident differentiation of silicone oil from hemorrhage as well as from other potential single-energy mimics, such as calcium and iodine.


Asunto(s)
Aceites de Silicona/química , Tomografía Computarizada por Rayos X/métodos , Diagnóstico Diferencial , Hemorragia/diagnóstico por imagen , Humanos , Interpretación de Imagen Asistida por Computador , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Desprendimiento de Retina/diagnóstico por imagen , Desprendimiento de Retina/tratamiento farmacológico , Aceites de Silicona/administración & dosificación , Aceites de Silicona/uso terapéutico
4.
J Comput Assist Tomogr ; 42(6): 824-830, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30371617

RESUMEN

Dual-energy computed tomography (DECT) has many current and evolving applications in neuroradiology including material decomposition, improving conspicuity of iodinated contrast enhancement, and artifact reduction. However, there are multiple challenges in incorporating DECT into practice including hardware selection, postprocessing software requirements, technologist and physician training, and numerous workflow issues. This article reviews in a question-and-answer format common issues that arise when incorporating DECT into a busy neuroradiology practice.


Asunto(s)
Neuroimagen/métodos , Administración de la Práctica Médica , Imagen Radiográfica por Emisión de Doble Fotón/estadística & datos numéricos , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Competencia Clínica , Toma de Decisiones , Humanos , Interpretación de Imagen Radiográfica Asistida por Computador , Programas Informáticos , Flujo de Trabajo
5.
Radiol Case Rep ; 18(12): 4569-4573, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37886728

RESUMEN

Sinonasal organized hematoma is a rare condition characterized by an organizing blood clot in the sinonasal cavity, which consists of blood products, fibrin, and dilated blood vessels. As a benign entity with an aggressive imaging appearance, it is important to differentiate sinonasal organized hematoma from malignancies affecting the paranasal sinuses and nasal cavities to guide appropriate management. In this report, we discuss the clinical presentation and diagnostic evaluation of an 82-year-old male with a left maxillary sinus organized hematoma and provide a comprehensive review of the relevant literature.

6.
A A Pract ; 16(12): e01649, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36599018

RESUMEN

Thoracic epidurals remain the optimal method for providing postoperative analgesia after complex open abdominal and thoracic surgeries. However, they can be challenging to both place and maintain, as evidenced by a failure rate that exceeds 30%.1 Proper identification of the epidural space and accurate placement of the catheter are critical in order to deliver effective postoperative analgesia and avoid failure.2,3 This case series investigated the difficulty in correctly identifying the proper vertebral level for thoracic epidural catheter procedures when performed in the lateral decubitus position.


Asunto(s)
Analgesia Epidural , Anestesia Epidural , Procedimientos Quirúrgicos Torácicos , Humanos , Analgesia Epidural/métodos , Anestesia Epidural/métodos , Espacio Epidural , Catéteres
7.
MedEdPORTAL ; 18: 11261, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35720637

RESUMEN

Introduction: Medical students often struggle with learning cranial nerve anatomy. Typically, cranial nerve anatomy is taught using didactic lectures and textbook illustrations, often leaving students frustrated. Methods: We developed a multimodal radiologic approach to teaching cranial nerve anatomy. First, 150 students were presented with carefully curated preclass material from which to prepare. Next, they received a didactic lecture that was recorded for them to revisit on their own time. Last, students worked in groups in a lab setting with expert radiologists to identify the cranial nerves and related anatomy and learn about some basic pathophysiology. We used a pretest and posttest to examine the effectiveness of our teaching methods and a survey to measure students' satisfaction. Results: Student knowledge of cranial nerve structure was significantly improved after our module, with quiz scores increasing from 4.6 to 6.8 out of 9.0 (p < .001). In addition, students reported feeling more confident in their knowledge of the material and offered high satisfaction scores. Discussion: The breadth of knowledge covered during the preclinical training years continues to expand despite stable or even contracted durations of training, requiring knowledge to be delivered in an ever more efficient manner. Ultimately, the multimodal pedagogy used by our resource leads to students who are more confident and engaged in their learning, resulting in increased knowledge.


Asunto(s)
Educación de Pregrado en Medicina , Radiología , Estudiantes de Medicina , Nervios Craneales/anatomía & histología , Educación de Pregrado en Medicina/métodos , Evaluación Educacional , Humanos , Radiología/educación
8.
Laryngoscope ; 132(9): 1792-1797, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35043989

RESUMEN

OBJECTIVES: Neck Imaging Reporting and Data System (NI-RADS) is a radiology reporting system for head and neck cancer surveillance. Imaging findings of high suspicion for recurrence are assigned Category 3 and recommended for "Biopsy, if clinically indicated." After implementing NI-RADS for surveillance neck computed tomography (CT), our objectives are to determine the incidence of squamous cell carcinoma (SCC) Category 3 lesions in the year post-implementation, the associated biopsy rate, and the positive predictive value of NI-RADS 3 for SCC recurrence. STUDY DESIGN: Retrospective cohort study. METHODS: Neck CTs reported with NI-RADS between February 2020 and February 2021 were reviewed to identify patients undergoing surveillance for SCC assigned NI-RADS 3. Cancer recurrence, defined as positive biopsy result or treatment of clinically determined recurrence, was determined by electronic medical record review. RESULTS: During the study period, 580 neck CTs were reported with NI-RADS, of which 39 (7%) CTs obtained in 37 unique patients (28 male, 9 female, mean age 66.6 years) formed the study cohort. Biopsies were obtained in 23 lesions (45%), of which 17 (74%) were positive for recurrent SCC. One nondiagnostic biopsy was clinically determined to represent recurrence. Of 28 (55%) lesions not biopsied, 18 (64%) were ultimately treated as clinically determined recurrence. Thus, among 51 individual NI-RADS 3 lesions (32 primary, 19 neck), 36 (71%) represented recurrence. CONCLUSION: The incidence of NI-RADS 3 lesions in our cohort was 7%. The biopsy rate was 45%, and the overall positive predictive value of NI-RADS 3 for recurrent SCC was 71%. Category 3 lesions are associated with substantial SCC recurrence risk and should be managed accordingly. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1792-1797, 2022.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Anciano , Biopsia , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/epidemiología , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/epidemiología , Humanos , Incidencia , Masculino , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/epidemiología , Tomografía Computarizada por Rayos X/métodos
9.
Oncol Lett ; 24(3): 326, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35949590

RESUMEN

Gorlin syndrome or nevoid basal cell carcinoma syndrome is a rare genetic disease characterized by predisposition to congenital defects, basal cell carcinomas and medulloblastoma. The syndrome results from a heritable mutation in PATCHED1 (PTCH1), causing constitutive activation of the Hedgehog pathway. The present study described a patient with Gorlin syndrome who presented early in life with characteristic basal cell carcinomas and later developed a small cell glioblastoma (GBM), World Health Organization grade IV, associated with a Patched 1 (PTCH1) N97fs*43 mutation. Comprehensive genomic profiling of GBM tissues also revealed multiple co-occurring alterations including cyclin-dependent kinase 4 (CDK4) amplification, receptor tyrosine-protein kinase 3 (ERBB3) amplification, a fibroblast growth factor receptor 1 and transforming acidic coiled-coil containing protein 1 (FGFR1-TACC1) fusion, zinc finger protein (GLI1) amplification, E3 ubiquitin-protein ligase (MDM2) amplification and spectrin α chain, erythrocytic 1 (SPTA1) T1151fs*24. After the biopsy, imaging revealed extensive leptomeningeal enhancement intracranially and around the cervical spinal cord due to leptomeningeal disease. The patient underwent craniospinal radiation followed by 6 months of adjuvant temozolomide (150 mg/m2) with good response. She was then treated with vismodegib for 11 months, first combined with temozolomide and then with bevacizumab, until disease progression was noted on MRI, with no significant toxicities associated with the combination therapy. She received additional therapies but ultimately succumbed to the disease four months later. The current study presents the first documentation in the literature of a primary (non-radiation induced) glioblastoma secondary to Gorlin syndrome. Based on this clinical experience, vismodegib should be considered in combination with standard-of-care therapies for patients with known Gorlin syndrome-associated glioblastomas and sonic hedgehog pathway mutations.

10.
Radiol Case Rep ; 14(9): 1103-1108, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31338135

RESUMEN

We present a case of a 63-year-old male with an 8-year history of a left-sided cystic facial mass which recurred despite multiple drainage procedures. Imaging findings showed a cystic mass in the left parotid gland and it was surgically resected. Pathology confirmed it to represent a mammary analogue secretory carcinoma, a relatively newly described entity. This case illustrates that mammary analogue secretory carcinoma can masquerade as a cyst within the parotid gland.

11.
Psychopharmacology (Berl) ; 200(4): 465-73, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18604521

RESUMEN

RATIONALE: To date, there is no medication specifically approved for cocaine addiction. Agonist medications are used clinically in the treatment of other addictions, which suggests that this method of drug therapy could potentially be successful in treating cocaine addiction as well. OBJECTIVE: The objective of this study was to determine the effect of extended D-amphetamine treatment on responding on a progressive ratio (PR) schedule reinforced by cocaine. MATERIALS AND METHODS: Rats were trained to self-administer cocaine (0.19, 0.38, 0.75, or 1.5 mg/kg/injection) or food on a PR schedule. After stable baseline breakpoints (the number of reinforcers earned in one session) were established over 3 days, animals were implanted with osmotic mini-pumps that continuously delivered D-amphetamine (5 mg/kg/day) for a duration of either 7 or 14 days. Breakpoints were then determined during and/or after this treatment period. RESULTS: Rats demonstrated dose-dependent decreases in cocaine-reinforced responding over the D-amphetamine treatment period. Breakpoints for doses of 0.75 mg/kg/injection and below decreased significantly when compared to baseline and remained decreased for up to 14 days after mini-pump removal, whereas those for the highest dose of cocaine remained unchanged. Additionally, D-amphetamine treatment during a 14-day abstinence period from cocaine self-administration had no effect on breakpoints when tested the day after mini-pump removal. CONCLUSIONS: These data suggest that the reduction in cocaine-reinforced responding after continuous D-amphetamine treatment cannot be accounted for by tolerance alone. Instead, the roles of learning and the interaction between cocaine and D-amphetamine must be considered and examined in future studies.


Asunto(s)
Estimulantes del Sistema Nervioso Central/farmacología , Trastornos Relacionados con Cocaína/tratamiento farmacológico , Cocaína/administración & dosificación , Dextroanfetamina/farmacología , Animales , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Masculino , Ratas , Ratas Sprague-Dawley , Esquema de Refuerzo , Autoadministración
12.
Psychopharmacology (Berl) ; 195(4): 517-25, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17879088

RESUMEN

RATIONALE: It has been hypothesized that sensitization of the neurochemical effects within the mesolimbic dopamine (DA) system might account for specific aspects of the addiction process. We have recently developed a self-administration procedure which produces increases in responding reinforced by cocaine on a progressive ratio (PR) schedule. This may reflect an increased motivation to self-administer cocaine, one hallmark of addiction. OBJECTIVES: The goal of this experiment was to investigate behavioral and neurochemical changes associated with increased cocaine self-administration on a PR schedule. MATERIALS AND METHODS: Rats self-administered cocaine over 14 days under a PR schedule. Cocaine-stimulated locomotor activity was evaluated before as well as 1 or 14 days after self-administration training. Cocaine-induced DA changes in the core and shell of the nucleus accumbens in the same animals were also examined. RESULTS: Subjects showed increased responding over time, to about 200% of baseline. Cocaine-induced locomotor activation was decreased at both withdrawal times compared to naïve animals. Microdialysis showed no differences after self-administration in the nucleus accumbens core dopamine response at either time point. There was, however, a significant decrease in the dopamine response to cocaine in the shell of the nucleus accumbens. CONCLUSION: The present results demonstrate that a progressive increase in breakpoints on a PR schedule can be established in rats at a time when the ability of cocaine to increase extracellular DA levels and stimulate locomotor activity is reduced. Therefore, sensitization of the mesolimbic DA system does not account for the observed change in drug-taking behavior.


Asunto(s)
Trastornos Relacionados con Cocaína/fisiopatología , Cocaína/administración & dosificación , Dopamina/metabolismo , Motivación , Actividad Motora/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Esquema de Refuerzo , Abuso de Sustancias por Vía Intravenosa/fisiopatología , Animales , Cocaína/toxicidad , Masculino , Microdiálisis , Actividad Motora/fisiología , Núcleo Accumbens/fisiopatología , Ratas , Ratas Sprague-Dawley , Autoadministración , Síndrome de Abstinencia a Sustancias/fisiopatología
13.
A A Pract ; 10(3): 53-56, 2018 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-28937422

RESUMEN

We report the use of continuous electrical stimulation to assist with the preoperative placement of a thoracic epidural which was used to provide postoperative analgesia in a patient undergoing excision of a large scapular sarcoma. The size of the sarcoma and the surrounding area required to maintain a sterile surgical field necessitated that the epidural catheter be inserted several vertebral interspaces caudal to the level of desired catheter tip termination. The use of electrical stimulation allowed for sequential intercostal muscle stimulation during threading, which enabled the placement of the catheter tip at the appropriate spinal level to optimize analgesia.

14.
Clin Imaging ; 45: 8-11, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28551487

RESUMEN

High resolution T2 magnetic resonance imaging (MRI) can provide exquisite detail of internal auditory canal (IAC) and cerebellopontine angle (CPA) lesions. In this retrospective case series, blinded imaging sequences were delivered to three radiologists and compared with previously archived clinical reads that were non-blinded and incorporated both T1+C and T2 sequences together. This article demonstrates high sensitivity and specificity for high resolution T2 MRI particularly with lesions >5mm. This suggests a role for high resolution T2 MRI as an initial screening sequence or as a surveillance sequence.


Asunto(s)
Enfermedades Cerebelosas/diagnóstico , Ángulo Pontocerebeloso , Oído Interno , Pérdida Auditiva Sensorineural/diagnóstico por imagen , Enfermedades del Laberinto/diagnóstico , Imagen por Resonancia Magnética/métodos , Enfermedades Cerebelosas/complicaciones , Enfermedades Cerebelosas/diagnóstico por imagen , Enfermedades Cerebelosas/patología , Ángulo Pontocerebeloso/diagnóstico por imagen , Ángulo Pontocerebeloso/patología , Oído Interno/diagnóstico por imagen , Oído Interno/patología , Femenino , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/patología , Humanos , Enfermedades del Laberinto/complicaciones , Enfermedades del Laberinto/diagnóstico por imagen , Enfermedades del Laberinto/patología , Masculino , Estudios Retrospectivos
15.
Ocul Oncol Pathol ; 3(3): 229-234, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29071274

RESUMEN

BACKGROUND: Leukemic infiltration of the optic nerve is relatively rare. While previously described in acute leukemia, the infiltration in our case represents central nervous system (CNS) metastasis of Burkitt-type lymphoma that developed as a complication of solid-organ transplantation, resulting in a bilateral infiltrative optic neuropathy with sequential, bilateral central retinal artery occlusion (CRAO) and devastating vision loss. METHODS: The medical record, serial ophthalmic examination findings, clinical course, and imaging including magnetic resonance imaging (MRI), fundus photographs, and fluorescein angiography of a single patient were retrospectively reviewed. RESULTS: MRI demonstrated multifocal cortical and leptomeningeal CNS involvement, including the left optic nerve. Serial fundus examination/photography and fluorescein angiography showed that despite urgent whole-brain irradiation and systemic chemotherapy, CNS disease progressed to bilateral optic nerve infiltration and CRAO with no light perception vision in both eyes. CONCLUSION: CRAO can occur as a devastating and irreversible complication of lymphoproliferative optic nerve infiltration.

16.
Neuropsychopharmacology ; 30(8): 1455-63, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15702135

RESUMEN

Despite large numbers of studies describing neuroadaptations caused by chronic cocaine exposure, there remains considerable uncertainty as to whether alterations in dopamine (DA) neurotransmission are responsible for progression into an addicted state. High-intake, 24-h access cocaine self-administration (SA, 10 days) followed by an extended (7 days), but not 1 day deprivation period produces an increased motivation to SA cocaine as measured by a progressive ratio protocol. Following binge cocaine SA and deprivation, the status of DA terminals in the nucleus accumbens (NAc) was investigated using microdialysis in freely moving rats and voltammetry in brain slices. At 1 and 7 days following binge cocaine SA, baseline extracellular DA concentrations in the NAc core were decreased by 40 and 55% of control levels, in the 1 and 7 day deprivation groups, respectively. Acute cocaine (1.5 mg/kg, i.v.) administration increased extracellular DA (350%) in the NAc core of naïve animals but failed to significantly increase DA at 1 or 7 days following binge cocaine SA. The shell of the NAc showed a similar lack of effect of cocaine. Analysis of DA terminals in brain slices showed that cocaine was markedly less effective in inhibiting DA uptake at 1 and 7 days of cocaine deprivation (max effect 40% of control). Electrically stimulated DA release was decreased at 1 day and further decreased at 7 days of deprivation (67 and 49% of control, respectively). The rate of DA uptake was increased (150% of control) following binge SA, irrespective of deprivation period. Finally, presynaptic autoreceptors were subsensitive at both time points, as measured by the ability of quinpirole, a D2-like DA receptor agonist, to inhibit DA release. Thus, the NAc was hypodopaminergic and DA terminals were less sensitive to cocaine following binge cocaine SA and deprivation.


Asunto(s)
Cocaína/administración & dosificación , Inhibidores de Captación de Dopamina/administración & dosificación , Dopamina/metabolismo , Terminales Presinápticos/efectos de los fármacos , Síndrome de Abstinencia a Sustancias/metabolismo , Animales , Conducta Animal , Química Encefálica/efectos de los fármacos , Agonistas de Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Interacciones Farmacológicas , Espacio Extracelular/efectos de los fármacos , Espacio Extracelular/metabolismo , Técnicas In Vitro , Masculino , Microdiálisis/métodos , Núcleo Accumbens/citología , Terminales Presinápticos/fisiología , Quinpirol/farmacología , Ratas , Ratas Sprague-Dawley , Autoadministración/métodos , Factores de Tiempo
17.
Cytometry A ; 57(2): 86-93, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-14750129

RESUMEN

BACKGROUND: Herceptin, a humanized antibody to HER-2, is now utilized in the clinic for metastatic breast cancer treatment. The response rate for HER-2+ patients is only 30% and little is known as to mechanisms of resistance. The mechanism of Herceptin action is also unknown but has been related to cell cycle inhibition. METHODS: The effects of Herceptin and other antibody treatments were determined by cell counting and cell cycle analysis. HER-2 and p27 expression levels were analyzed by flow cytometry and levels of activated AKT were compared by Western blot analysis. Cellular HER-2 and p27 expression was measured by immunofluorescence. RESULTS: Herceptin treatment of BT-474 cells results in inhibition of cell growth and arrest in the G1 phase. The efficacy of growth arrest was not directly correlated to the binding affinity of antibodies to Her-2. Our laboratory has developed cell lines that are resistant to Herceptin treatment. In resistant cell lines, binding of antibodies is not hindered. However, Herceptin has completely lost the ability to inhibit cell proliferation. Yet, the mouse isotype 4D5 maintains significant inhibitory activity upon Herceptin-resistant clones. CONCLUSIONS: Herceptin binds effectively to Her-2 on the cell surface of Herceptin-resistant cell lines and the level of Her-2 expression on the cell surface is not downregulated. Herceptin resistance is not due to downregulation of levels of AKT protein expression, although, phosphorylation of AKT is enhanced in resistant lines and could have a role in resistance. Resistance appears to correlate with the loss of nuclear expression of the cyclin-dependent kinase inhibitor, p27, as defined by immunofluorescence and flow cytometry studies and cdk-2 binding studies.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos , Animales , Anticuerpos Monoclonales/metabolismo , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/metabolismo , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Regulación hacia Abajo , Receptores ErbB/metabolismo , Femenino , Citometría de Flujo , Humanos , Ratones , Trastuzumab , Proteínas Supresoras de Tumor/metabolismo
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