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1.
J Emerg Med ; 55(4): 547-552, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30181074

RESUMEN

BACKGROUND: Humerus fractures caused by the throwing motion are extremely rare. They have been reported mostly in recreational adult athletes in their third or later decades of life. A pediatric thrower's fracture is even less common, with few reported cases. The pediatric version of this fracture is located in the proximal to midshaft humerus, distinguishing it from the adult type, which occurs in the middle to distal shaft. CASE REPORT: A 12-year-old male pitcher experienced a "snap" in his right arm while throwing a pitch in a baseball game. He presented to the Emergency Department with right arm pain and deformity. He was misdiagnosed with a right glenohumeral dislocation and a reduction maneuver was attempted prior to any radiographic imaging. Upon further review of the imaging and outpatient follow-up, he was found to have a humeral spiral fracture consistent with a "ball-thrower's fracture." The fracture healed with conservative treatment and he returned to unrestricted sports participation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Recognition of this fracture is important to avoid unnecessary and potentially harmful treatment of the pediatric patient. A thrower's fracture of the pediatric humerus is rare, but glenohumeral dislocation without direct trauma is even less common and has never been reported as a result of the throwing motion in a pediatric patient. Radiographic imaging is important, and consideration of the thrower's fracture should be in the differential for any patient presenting with acute pain and deformity of the arm resulting from throwing any object.


Asunto(s)
Fracturas Óseas/clasificación , Fracturas Óseas/diagnóstico , Húmero/lesiones , Traumatismos en Atletas/diagnóstico , Traumatismos en Atletas/diagnóstico por imagen , Traumatismos en Atletas/etiología , Béisbol/lesiones , Niño , Diagnóstico Tardío , Servicio de Urgencia en Hospital/organización & administración , Fracturas Óseas/diagnóstico por imagen , Humanos , Masculino , Dolor/etiología , Pediatría/métodos , Radiografía/métodos , Radiografía/normas
2.
Oncogene ; 37(27): 3672-3685, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29622797

RESUMEN

BMP receptor inhibitors induce death of cancer cells through the downregulation of antiapoptotic proteins XIAP, pTAK1, and Id1-Id3. However, the current most potent BMP receptor inhibitor, DMH2, does not downregulate BMP signaling in vivo because of metabolic instability and poor pharmacokinetics. Here we identified the site of metabolic instability of DMH2 and designed a novel BMP receptor inhibitor, JL5. We show that JL5 has a greater volume of distribution and suppresses the expression of Id1 and pTak1 in tumor xenografts. Moreover, we demonstrate JL5-induced tumor cell death and tumor regression in xenograft mouse models without immune cells and humanized with adoptively transferred human immune cells. In humanized mice, JL5 additionally induces the infiltration of immune cells within the tumor microenvironment. Our studies show that the BMP signaling pathway is targetable in vivo and BMP receptor inhibitors can be developed as a therapeutic to treat cancer patients.


Asunto(s)
Antineoplásicos/farmacología , Receptores de Proteínas Morfogenéticas Óseas/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Pirazoles/farmacología , Pirimidinas/farmacología , Quinolonas/farmacología , Microambiente Tumoral/efectos de los fármacos , Células A549 , Traslado Adoptivo , Animales , Antineoplásicos/química , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Proteína 1 Inhibidora de la Diferenciación/biosíntesis , Neoplasias Pulmonares/patología , Quinasas Quinasa Quinasa PAM/biosíntesis , Ratones , Ratones Endogámicos NOD , Ratones SCID , Inhibidores de Proteínas Quinasas/química , Pirazoles/química , Pirazoles/uso terapéutico , Pirimidinas/química , Pirimidinas/uso terapéutico , Quinolonas/química , Quinolonas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Cell Rep ; 17(4): 957-965, 2016 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-27760326

RESUMEN

In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8+ T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1). Immunotherapy to block PD-1 reverses this loss of anti-tumor CD8+ T cells from the tumor and decreases infection-induced tumor growth. Our findings show that acute non-oncogenic infection can promote cancer growth, raising concerns regarding acute viral illness sequelae. They also suggest an unexpected role for PD-1 blockade in cancer immunotherapy and provide insight into the immune response when faced with concomitant challenges.


Asunto(s)
Melanoma/inmunología , Melanoma/patología , Oncogenes , Infecciones por Orthomyxoviridae/patología , Enfermedad Aguda , Animales , Linfocitos T CD8-positivos/inmunología , Proliferación Celular , Pulmón/patología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Receptor de Muerte Celular Programada 1/metabolismo
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