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1.
Arch Pathol Lab Med ; 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38353277

RESUMEN

CONTEXT.­: Social media has become widely adopted by pathologists and other physicians for professional purposes. While engagement has likely increased over time, there remain few concrete data regarding attitudes toward its use. OBJECTIVE.­: To assess pathologists' use of and attitudes toward social media over time. DESIGN.­: We created a survey regarding personal and professional use of social media and circulated it via multiple channels in December 2017 and again in February 2022. Results of the 2 surveys were compared for statistically significant differences. RESULTS.­: The 2017 survey was completed by 97 participants, and the 2022 survey by 305 participants. Respondents were predominantly female and academics, included pathologists in all age categories and all time-in-practice length. In both surveys, Twitter (now X) was the most popular platform for professional use and Facebook was the most popular for personal use. Professional barriers to social media use remained consistent between the 2 surveys, including the amount of time required. Education was seen as the main benefit of social media use in both surveys, while other benefits such as networking and increasing professional visibility were endorsed significantly less often in the second survey. While the second survey received more than 3 times as many responses as the first, several aspects of social media use (mainly demographics) remained similar during the timeframe, while other aspects (such as usage and perceived values) decreased. CONCLUSIONS.­: Pathologists continue to find social media valuable. Barriers remain, though overall pathologists of all ages and practice settings appear receptive to using social media to further educational and other opportunities.

2.
Ear Nose Throat J ; 102(7): NP303-NP307, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33973483

RESUMEN

Rosai-Dorfman disease (RDD) is a rare benign systemic histiocytic proliferation characterized by massive lymph node enlargement and sometimes associated with extranodal involvement. Even though it is considered to be benign, death can occur depending on the extent and location. Our case highlights a primary extranodal site of the right pinna with extension through the Eustachian tube to the subglottis. A previously healthy 15-year-old female presented with 1-year right pinna swelling, slowly enlarging and becoming more bothersome. An incisional biopsy was performed on the ear along with S100 staining yielding a diagnosis. After multidisciplinary case discussion, clofarabine monotherapy and systemic therapy for Langerhans cell histiocytosis has started. Rosai-Dorfman disease can be a general disorder, often affecting the lymph nodes. Unlike a nodal disease, extranodal disease could involve any site on the patient's anatomy. Head and neck lesions are the most common extranodal lesions. Rosai-Dorfman disease is self-limited in more than 20% of the cases with spontaneous regression without intervention; 70% of the patients have noticeable symptoms and vital organ involvement requiring treatments such as surgery, steroids, radiation, and chemotherapy. In our case, the patient had wide involvement and presented without any serious breathing difficulties; we decided to start with monotherapy with chemotherapy and systematic glucocorticoid treatment.


Asunto(s)
Histiocitosis Sinusal , Linfadenopatía , Femenino , Humanos , Adolescente , Histiocitosis Sinusal/diagnóstico , Histiocitosis Sinusal/patología , Cuello/patología , Ganglios Linfáticos/patología , Oído Externo/patología
3.
J Am Soc Cytopathol ; 12(1): 20-29, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36270912

RESUMEN

INTRODUCTION: In children and adolescents, most sarcoma subtypes have a simple karyotype with a single genetic alteration; cytologic findings combined with ancillary testing can lead to a specific diagnosis. The goal of this study was to review the use of fine-needle aspiration in conjunction with immunohistochemistry and molecular studies as a part of an integrated, multidisciplinary diagnostic workup for bone and soft tissue sarcomas in this population. MATERIALS AND METHODS: We searched for cases aged ≤18 years old with a malignant bone or soft tissue tumor that had corresponding cytology specimens from 3 institutions. Clinical data, cytologic findings and diagnoses, histologic diagnoses, and ancillary testing were documented. RESULTS: Of 99 cases, 55% were male with a mean age of 12 years. Ninety-four cases (95%) had a specific histologic diagnosis, and 84 cases (85%) were primary neoplasms. Ninety-four cases (95%) had a malignant cytologic diagnosis, and 71 cases (72%) had a specific cytologic diagnosis concordant with the histologic diagnosis. Among primary tumors with a specific histologic diagnosis, a specific cytologic diagnosis was made in 63 cases (79%). After excluding osteosarcoma, 74% of the tumors (n = 50) had molecular studies. Specific genetic alterations supporting a definitive diagnosis were found in 42 cases (84%), the majority of which were demonstrated using Fluorescence In Situ Hybridization (n = 33, 79%). CONCLUSIONS: We found that fine-needle aspiration in conjunction with core needle biopsy, immunohistochemistry, and molecular studies allowed cytopathologists to accurately classify sarcomas in a pediatric age group.


Asunto(s)
Neoplasias Óseas , Sarcoma , Neoplasias de los Tejidos Blandos , Adolescente , Niño , Femenino , Humanos , Masculino , Biopsia con Aguja Fina , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Citología , Hibridación Fluorescente in Situ , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patología , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología
4.
Urol Case Rep ; 43: 102116, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35646598

RESUMEN

The following case report describes a case of prostatic rhabdomyosarcoma in a 6-month-old male who presented with urinary retention and constipation. MRI showed a prostatic mass that was displacing the rectum and bladder, leading to bladder outlet obstruction. A suprapubic tube was placed for urinary diversion and a transvesical approach was used for tissue diagnosis. Biopsy confirmed the diagnosis of prostatic rhabdomyosarcoma. Patient underwent chemotherapy regiment with VAC (vincristine, actinomycin D and cyclophosphamide) and subsequently ifosfamide and doxorubicin. Eventually, due to tumor progression, the patient underwent a radical cystoprostatectomy with pelvic lymph node dissection and ileal conduit.

5.
Pediatr Dev Pathol ; 25(5): 499-503, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35400217

RESUMEN

INTRODUCTION: Appendicular foreign bodies are a rare, under-described cause of appendicitis. We performed this study to determine the varied causes and consequences of foreign-body appendicitis. METHODS: On retrospective review of the pathology archives of seven institutions, we identified 56 appendix specimens containing a foreign body (defined as ingested, non-digestible material). We recorded the type of foreign body, patient age and sex, and other findings, as available. RESULTS: Mean patient age was 7.7 years (range: 1 day-18 years). The foreign bodies included hair, plant material, magnets, other metallic material, BB pellets, foreign material not otherwise specified, and other miscellaneous objects. Of 48 cases with available clinical information, 31 patients presented with abdominal pain, and 22 were preoperatively diagnosed as having appendicitis/appendicular inflammation. Seven patients had appendiceal perforation (13%). The foreign body was grossly identified in 34/47 cases with available gross descriptions. Twenty-seven cases had an identifiable foreign body microscopically; 10 were associated with giant cell reaction. DISCUSSION: Hair and plant materials were the most common foreign objects found in the appendix; they often cause mucosal damage and giant cell reaction. Metallic objects were less common. Although appendicular foreign bodies in children are rare and sometimes asymptomatic, they may lead to perforation.


Asunto(s)
Apendicitis , Apéndice , Cuerpos Extraños , Apendicitis/diagnóstico , Apendicitis/etiología , Apendicitis/cirugía , Apéndice/cirugía , Niño , Cuerpos Extraños/complicaciones , Cuerpos Extraños/diagnóstico , Humanos , Lactante , Inflamación
7.
Cancer Cytopathol ; 129(11): 884-892, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34076955

RESUMEN

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) provides a useful framework for the diagnosis of salivary gland fine-needle aspiration (FNA) biopsies. In this study, the MSRSGC was applied to salivary gland FNAs in pediatric patients to assess its usefulness and look at pitfalls. METHODS: The laboratory information system was queried over a 15-year period for all salivary gland FNAs in patients 18 years old or younger. Patient demographics, FNA diagnosis categorized according to the MSRSGC, and follow-up surgical pathology diagnoses were examined and correlated. RESULTS: Thirty-two cases were identified, with an average age of 12 years (range, 0.6-18 years). A majority of the cases (84.4%) were from the parotid region. Twenty of 32 cases (62.5%) had follow-up resection. MSRSGC recategorization diagnoses of the 32 FNA cases were 34% benign neoplasm, 31% nonneoplastic, 16% nondiagnostic, 9% atypia of undetermined significance, 3% salivary neoplasm of uncertain malignant potential, 3% suspicious for malignancy, and 3% malignant. Overall, the sensitivity and specificity were 100% and 80%, respectively. On follow-up resection, 55% were neoplastic: pleomorphic adenomas (n = 6; 55%), pilomatricoma (n = 3; 28%), mucoepidermoid carcinoma (n = 1; 9%), schwannoma (n = 1; 9%), and myofibroma (n = 1; 9%). CONCLUSIONS: The MSRSGC performed fairly well in the pediatric population with a low overall risk of malignancy (6%) and high sensitivity. Although the majority of pediatric salivary gland FNAs were benign, 55% of resected cases were positive for a neoplasm, with benign neoplasms outnumbering malignancy. Challenging entities included inflammatory conditions, like immunoglobulin G4-related sialadenitis, and skin and soft tissue lesions near the salivary gland.


Asunto(s)
Neoplasias de las Glándulas Salivales , Adolescente , Biopsia con Aguja Fina , Niño , Hospitales , Humanos , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales/patología
8.
Pediatrics ; 146(5)2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33115794

RESUMEN

An 11-year-old girl with a congenitally malformed left hand, sickle cell trait, asthma, and history of appendicitis was transferred from Zambia for evaluation and treatment of widespread suppurative and ulcerative skin lesions that typically appeared after trauma to her skin. The ulcers first presented 3 years earlier but had markedly worsened in the 9 months before transfer, spreading circumferentially on her extremities and abdomen at the site of an appendectomy. They were painful and did not resolve with multiple courses of intravenous antibiotics and close management by a pediatric infectious disease specialist working for a nongovernmental organization (NGO) in her home country. Per NGO records, she had previously been  average weight-for-age. On presentation after international transfer, she was severely malnourished, with lesions covering âˆ¼35% of her body. In initial workup, leukocytosis of 21 × 103 cells per µL (79% neutrophils), hemoglobin of 6.1 g/dL, and mean corpuscular volume of 66 fL were found. Iron studies revealed an iron level of 18 µg/dL, ferritin level of 55 ng/mL, total iron binding capacity of 222 µg/dL, and transferrin saturation of 8%. Inflammatory markers were elevated, C-reactive protein was 20.1 mg/dL, and the erythrocyte sedimentation rate was 131 mm/h. A chest computed tomography scan revealed bilateral pulmonary nodules, the largest in her left upper lobe measuring 2.4 × 2.0 × 1.9 cm. Our panel of experts reviews the evaluation and treatment of this patient with extensive suppurative and ulcerative skin lesions and the factors considered in offering charity care to international patients.


Asunto(s)
Desnutrición/complicaciones , Piodermia Gangrenosa/diagnóstico , Piodermia Gangrenosa/etiología , Úlcera Cutánea/etiología , Niño , Enfermedad Crónica , Femenino , Humanos , Zambia
9.
Ophthalmic Plast Reconstr Surg ; 36(3): e65-e68, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31880682

RESUMEN

Inflammatory myofibroblastic tumor is a mesenchymal neoplasm, commonly seen in the lung and abdominopelvic region of children. The authors present an 8-month-old female with a 2-month history of left-sided proptosis. Examination was significant for left-sided proptosis, a left exotropia and hypotropia, left supraduction and adduction deficits, and left optic disc elevation. MRI imaging revealed an extraconal left superomedial orbital mass with globe displacement and proptosis. Left anterior orbitotomy with excisional biopsy showed a solid mass composed of an infiltrative proliferation of bland spindle cells in a variably myxoid background with associated perivascular lymphoplasmacytic infiltration. Immunohistochemistry was positive for ALK-1 and CD34 and demonstrated focal positivity for S100. Fluorescence in-situ hybridization showed an additional copy of the 3'ALK gene (46%) in interphase cells examined. Next generation targeted sequencing found a DCTN1/ALK fusion. Findings were consistent with inflammatory myofibroblastic tumor. To the authors' knowledge, this is one of the largest primary orbital inflammatory myofibroblastic tumors in the youngest reported patient.


Asunto(s)
Neoplasias de Tejido Muscular/diagnóstico , Órbita , Biomarcadores de Tumor , Niño , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Lactante , Órbita/patología
10.
Pediatr Dev Pathol ; 23(3): 215-221, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31619135

RESUMEN

BACKGROUND: The clinical significance of a diagnosis of granulomatous appendicitis (GA) is not well established in the pediatric population. METHODS: Retrospective review of the etiology and histopathology of pediatric GA at 2 large pediatric institutions. RESULTS: Forty-three (0.4%) patients had GA at a median age of 12.1 years. Twenty-two (51%) had perforated appendicitis that was medically managed prior to interval appendectomy. Sixteen of 21 noninterval appendectomies were performed for clinically suspected acute appendicitis. Among them, 1 had Crohn's disease identified during surgery. None of the other patients had a subsequent diagnosis of inflammatory bowel disease (median follow-up of 4 weeks). There were significantly more cases with mucosal-only granulomas as well as fewer serosal granulomas in the noninterval appendectomy specimens than the interval specimens (P = .014). When performed, special stains for microorganisms did not contribute to clinical care. In the same time period, GA was seen in 6 (6%) of 94 bowel resections for Crohn's disease. CONCLUSION: GA is rare in pediatric patients, with interval appendectomy being the most common etiology and only rarely associated with Crohn's disease. Granulomas in interval appendectomies tend to be serosal-based. Special stains for infectious organisms in GA are of low diagnostic yield and have little impact on clinical management.


Asunto(s)
Apendicectomía/métodos , Apendicitis/patología , Apendicitis/cirugía , Granuloma/patología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos
12.
Arch Pathol Lab Med ; 142(2): 178-183, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28537807

RESUMEN

CONTEXT: - Thyroid nodules have a prevalence of approximately 70% in adults. Fine-needle aspiration (FNA) is a minimally invasive, cost-effective, standard method to collect tissue from thyroid nodules for cytologic examination. However, approximately 15% of thyroid FNA specimens cannot be unambiguously diagnosed as benign or malignant. OBJECTIVE: - To investigate whether clinically actionable data can be obtained using next-generation sequencing of residual needle rinse material. DESIGN: - A total of 24 residual needle rinse specimens with malignant (n = 6), indeterminate (n = 9), or benign (n = 9) thyroid FNA diagnoses were analyzed in our clinical molecular diagnostics laboratory using next-generation sequencing assays designed to detect gene mutations and translocations that commonly occur in thyroid cancer. Results were correlated with surgical diagnoses and clinical outcomes. RESULTS: - Interpretable data were generated from 23 of 24 residual needle rinse specimens. Consistent with its well-known role in thyroid malignancy, BRAF V600E mutations were detected in 4 malignant cases. An NRAS mutation was detected in 1 benign case. No mutations were detected from specimens with indeterminate diagnoses. CONCLUSIONS: - Our data demonstrate that residual thyroid FNA needle rinses are an adequate source of material for molecular diagnostic testing. Importantly, detection of a mutation implicated in thyroid malignancy was predictive of the final surgical diagnosis and clinical outcome. Our strategy to triage thyroid nodules with indeterminate cytology with molecular testing eliminates the need to perform additional FNA passes into dedicated media or to schedule additional invasive procedures. Further investigation with a larger sample size to confirm the clinical utility of our proposed strategy is underway.


Asunto(s)
Biopsia con Aguja Fina/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/genética , Citodiagnóstico/métodos , Análisis Mutacional de ADN/métodos , Humanos , Técnicas de Diagnóstico Molecular/métodos , Mutación
13.
J Am Soc Cytopathol ; 7(4): 219-223, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-31043280

RESUMEN

Social media includes electronic communications shared in virtual communities and networks. In recent years, medical professionals and trainees have used social media to promote medical education, networking, scientific communication, and more. This practice has grown in medicine in general, including in pathology and cytopathology. Twitter, a social media platform where users compose short "tweets," is a popular platform for medical professionals, including "live-tweeting," where users post real-time updates from a conference using a conference-specific hashtag. For the 65th ASC Annual Scientific Meeting, the hashtag #ASCyto17 was selected. The specific hashtag allows users to easily browse all of the tweets from the meeting, and additionally enables hashtag-specific analytic data via the Symplur Healthcare Hashtags Project. Over the 4 days of the meeting, there were over 6 million impressions (potential tweet-views) from #ASCyto17, from 2514 tweets generated by 285 unique participants. Tweets included sharing practice updates, cases from the Diagnostic Cytology Seminar, and "cell-fies" with friends and colleagues. Through social media, the reach of the ASC meeting was greatly expanded, with potential benefits to ASC members and non-members alike.

14.
J Am Soc Cytopathol ; 7(3): 142-148, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-31043309

RESUMEN

INTRODUCTION: High-risk human papillomavirus (hrHPV) testing is important in cervical cancer screening and management algorithms. Roche (Pleasanton, Calif.) cobas hrHPV testing is commonly performed on both ThinPrep (TP) and SurePath (SP) samples, but performance of these platforms has not been fully investigated in the literature. MATERIALS AND METHODS: Roche hrHPV testing was performed on 47,885 (TP = 18,295; SP = 29,590) out of 130,648 consecutive Papanicolaou tests, over 16 months; 1895 of those had interpretable biopsies. RESULTS: The overall hrHPV detection rates were similar in TP (13.5%) and SP (13.1%). The hrHPV positive rate was higher in SP (8.5%) than TP (7.3%, P < 0.0001) in women with negative cytology; the difference in other cytologic diagnosis categories was insignificant. TP samples had significantly fewer negative cytology diagnoses (7.3% versus 8.5%, P < 0.0001), more low-grade abnormalities in cytology and biopsies, and higher colposcopy referral rate (4.8% versus 2.7%, P < 0.0001) than SP. There were no differences between TP and SP in detecting ≥HSIL by hrHPV testing, cytology or biopsy. SP samples had a significantly higher rate of HPV 16/18 but a lower rate of non-16/18 hrHPV genotypes than TP. CONCLUSIONS: Roche cobas hrHPV testing was similar in both TP and SP platforms. The significantly lower hrHPV detection rate in cytological negative TP samples is likely related to higher cytology reporting rates for indeterminate and low-grade diagnoses in TP than SP samples. Significant differences were also observed in hrHPV genotyping results between TP and SP. Clinical risk stratification based on hrHPV testing may need to take testing platforms into consideration.

16.
Arch Pathol Lab Med ; 140(11): 1273-1280, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27441785

RESUMEN

Periscope is a live video-streaming smartphone application (app) that allows any individual with a smartphone to broadcast live video simultaneously to multiple smartphone users around the world. The aim of this review is to describe the potential of this emerging technology for global pathology education. To our knowledge, since the launch of the Periscope app (2015), only a handful of educational presentations by pathologists have been streamed as live video via Periscope. This review includes links to these initial attempts, a step-by-step guide for those interested in using the app for pathology education, and a summary of the pros and cons, including ethical/legal issues. We hope that pathologists will appreciate the potential of Periscope for sharing their knowledge, expertise, and research with a live (and potentially large) audience without the barriers associated with traditional video equipment and standard classroom/conference settings.

17.
Arch Pathol Lab Med ; 140(9): 956-7, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27195434

RESUMEN

Social media use is very common and can be an effective way for professionals to discuss information and interact with colleagues. Twitter (Twitter, Inc, San Francisco, California) is a social media network where posts, termed tweets, are limited to 140 characters. Professional use of Twitter is ideal for physicians interested in both networking and education and is optimally used to facilitate in-person networking. Live-tweeting (posting real-time reactions to events) at professional meetings is also a popular and highly successful use of Twitter. Physicians report patient privacy as the top concern preventing use of social media for professional reasons, and although generally social media use is safe, it is essential to understand how to protect patient confidentially. Other social media platforms with potential for professional use include Facebook (Facebook, Inc, Menlo Park, California), Instagram (Facebook, Inc), YouTube (YouTube, LLC, San Bruno, California), and Periscope (Twitter, Inc). With Twitter and other social media options, now is the time for pathologists to increase our visibility on social media and worldwide.


Asunto(s)
Comunicación , Confidencialidad , Relaciones Médico-Paciente , Medios de Comunicación Sociales/estadística & datos numéricos , Humanos , Patología Clínica/métodos , Patología Clínica/tendencias
18.
J Am Soc Cytopathol ; 5(6): 339-344, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-31042545

RESUMEN

INTRODUCTION: Pleural and peritoneal/ascites fluid samples with many lymphocytes are commonly received in the cytology laboratory. It is often difficult to distinguish reactive lymphocytes from hematopoietic malignancy based on morphology alone, however. Flow cytometry can be a useful adjunct in body fluids, although literature on this subject is limited. MATERIALS AND METHODS: This study is a single-institution 5-year retrospective review of 377 fluid samples from 341 patients with corresponding flow cytometry analysis. The cytologic findings were correlated with the flow cytometry results and clinical data, as available. RESULTS: Of 4158 pleural fluids received over 5 years, 325 (7.8%) had corresponding flow cytometry analysis. Of these 325 samples, 57 (17.5%) were positive for hematopoietic malignancy by flow cytometry. Of the positive cases, only 24 (8.7%) represented a new diagnosis of hematopoietic malignancy (ie, did not have a known history). Of 3020 peritoneal/ascites fluids received over 5 years, 52 (2%) had corresponding flow cytometry. Of these, 8 were positive for hematopoietic malignancy, and only 2 represented a presumed new diagnosis. CONCLUSIONS: Routine flow cytometry analysis for pleural and peritoneal/ascitic fluids is of limited utility, with only rare cases positive for hematopoietic malignancy without a known history. Of these cases, many had atypical cells that suggested a positive diagnosis. Conversely, in cases with a known history, about 75% were positive for hematopoietic malignancy. Our study suggests that the utility of flow cytometry for pleural and peritoneal/ascitic fluids is limited, and should be used sparingly in cases without atypical cytologic features, high clinical suspicion, or known history.

19.
Cardiovasc Pathol ; 23(6): 351-3, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25130767

RESUMEN

A 15-year-old African-American female with a 4-month history of sporadic rapid heartbeat and fatigue was found pulseless and apneic in her residence. At autopsy, patchy scarring was diffuse throughout the circumference of the left ventricle of the heart. Microscopically, the myocardium had diffuse infiltration of rhabdomyoma-like cells with significant associated fibrosis. Unlike cardiac rhabdomyoma, there was no discrete tumor mass. Differential diagnoses considered were congenital cardiac rhabdomyoma with partial regression, cardiac fibroma, histiocytoid cardiomyopathy, glycogen storage diseases, and drug-induced vacuolar cardiomyopathy. However, the findings are most consistent with cardiac rhabdomyomatosis, an entity not well described in the literature.


Asunto(s)
Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/patología , Neoplasias Cardíacas/complicaciones , Neoplasias Cardíacas/patología , Rabdomioma/complicaciones , Rabdomioma/patología , Adolescente , Autopsia , Cardiomiopatías/etiología , Cardiomiopatías/patología , Diagnóstico Diferencial , Femenino , Fibrosis , Ventrículos Cardíacos/patología , Humanos
20.
J Clin Invest ; 121(3): 893-904, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21285512

RESUMEN

The transcription factor p53 is a tumor suppressor. As such, the P53 gene is frequently altered in human cancers. However, over 80% of the P53 mutations found in human cancers are missense mutations that lead to expression of mutant proteins that not only lack p53 transcriptional activity but exhibit new functions as well. Recent studies show that restoration of p53 expression leads to tumor regression in mice carrying p53 deletions. However, the therapeutic efficacy of restoring p53 expression in tumors containing p53 missense mutations has not been evaluated. Here we demonstrate that restoring wild-type p53 expression halted tumor growth in mice inheriting a p53(R172H) missense mutation that is equivalent to a P53 missense mutation detected in approximately 6% of human cancers. However, it did not lead to tumor regression, as was observed in mice lacking p53. We further showed that the dominant-negative effect of the mutant p53 encoded by p53(R172H) dampened the activity of the restored wild-type p53. We therefore conclude that in a mutant p53 background, p53 restoration has the therapeutic potential to suppress tumor progression. Our findings support using p53 restoration as a strategy to treat human cancers with P53 missense mutations and provide direction for optimizing p53 restoration in cancer therapy.


Asunto(s)
Eliminación de Gen , Regulación Neoplásica de la Expresión Génica , Genes p53 , Mutación Missense , Neoplasias/genética , Proteína p53 Supresora de Tumor/genética , Células 3T3 , Alelos , Animales , Femenino , Genes Dominantes , Genes Supresores de Tumor , Intrones , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Neoplasias/terapia , Transcripción Genética
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