RESUMEN
Hepatocellular carcinoma (HCC) has a recurrence rate of up to 70% in 5 years after resection, detrimentally lowering survival. The role of adjuvant therapy remains controversial; therefore, the aim of this study was to evaluate the disease-free and overall survival of patients with HCC, not candidates for transplantation, undergoing resection and adjuvant hepatic artery infusion therapy vs resection alone. Our meta-analysis showed that adjuvant HAIC improves overall and disease-free survival after resection, especially in tumors ≥7 cm.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Anciano , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Arteria Hepática , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana EdadRESUMEN
Hamstring muscle injuries (HMI) are common among athletes. HMI can take many months to years to resolve. Often, athletes do not report complete resolution with typical conservative therapy. We present several cases of athletes who presented with chronic hamstring injuries that resolved immediately after being treated with an ultrasound-guided fascial hydrodissection procedure. Following the procedure and graded rehabilitation protocol, athletes reported resolution of pain and tightness in addition to increased performance and a quicker return to play.
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Traumatismos en Atletas/cirugía , Disección/métodos , Músculos Isquiosurales/lesiones , Traumatismos de la Pierna/cirugía , Traumatismos de los Tejidos Blandos/cirugía , Adolescente , Adulto , Atletas , Femenino , Humanos , Masculino , UltrasonografíaAsunto(s)
Centros Médicos Académicos/organización & administración , Servicios de Salud Comunitaria/organización & administración , Enfermeras Practicantes/organización & administración , Rol de la Enfermera , Grupo de Atención al Paciente/organización & administración , Enfermedades Vasculares/enfermería , Humanos , Enfermedades Vasculares/diagnósticoAsunto(s)
Golf/lesiones , Enfermedades Cutáneas Vasculares/etiología , Vasculitis/etiología , Caminata , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recurrencia , Factores de Riesgo , Enfermedades Cutáneas Vasculares/diagnóstico , Enfermedades Cutáneas Vasculares/terapia , Vasculitis/diagnóstico , Vasculitis/terapiaRESUMEN
BACKGROUND: Previous studies showed that proline-rich polypeptide (PRP-1) is a ligand for innate immunity toll-like receptors (TLR), and an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) which induces the death of chondrosarcoma cancer stem cells (CSC). The aim of this study was to investigate the effect of PRP-1 on the regulation of unfolded protein response (UPR) in human chondrosarcoma cells. MATERIALS AND METHODS: Lysates were prepared from a monolayer (bulk or ALDHhigh population), or spheroids chondrosarcoma cell cultures and treated with PRP-1 or control, followed by protein levels quantification by western blotting and mRNA expression by RT-qPCR of protein-RNA-like endoplasmic reticulum kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), CCAAT-enhancer-binding protein homologous protein (CHOP), activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1α), and X-box binding protein (XBP1). RESULTS: The PRP-1 has been shown to increase the expression of PERK, eIF2α, ATF4, CHOP, ATF6, IRE1α, and XBP1, on both protein and mRNA levels. CONCLUSION: PRP-1 activated UPR branches in monolayer, spheroid, and stem cell populations of human chondrosarcoma.
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Neoplasias Óseas , Condrosarcoma , Receptores Toll-Like , Respuesta de Proteína Desplegada , Humanos , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Ligandos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Mensajero/farmacología , Transducción de Señal , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Respuesta de Proteína Desplegada/genética , Respuesta de Proteína Desplegada/fisiología , Condrosarcoma/genética , Condrosarcoma/metabolismo , Condrosarcoma/patología , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patologíaRESUMEN
Coronavirus disease of 2019 poses significant risks for patients with vascular disease. Telemedicine can help clinicians provide care for patients with vascular disease while adhering to social-distancing guidelines. In this article, we review the components of telemedicine used in the vascular medicine practice at the Vanderbilt University Medical Center. In addition, we describe inpatient and outpatient diagnosis-based algorithms to help select patients for telemedicine versus in-person evaluation.
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COVID-19/prevención & control , Cardiología/normas , Atención a la Salud/normas , Pandemias/prevención & control , Guías de Práctica Clínica como Asunto , Servicios Preventivos de Salud/normas , Telemedicina/normas , Cardiología/métodos , Atención a la Salud/métodos , Humanos , Servicios Preventivos de Salud/métodos , SARS-CoV-2 , Telemedicina/métodos , TennesseeRESUMEN
Chondrosarcoma is a malignant bone neoplasm that is refractory to chemotherapy and radiation. With no current biological treatments, mutilating surgical resection is the only effective treatment. Proline rich polypeptide 1 (PRP1), which is a 15amino acid inhibitor of mammalian target of rapamycin complex1 (mTORC1), has been indicated to exert cytostatic and immunomodulatory properties in human chondrosarcoma cells in a monolayer. The aim of the present study was to evaluate the effects of PRP1 on an in vitro 3D chondrosarcoma tumor model, known as spheroids, and on the cancer stem cells (CSCs) which form spheroids. JJ012 cells were cultured and treated with PRP1. An ALDEFLUOR™ assay was conducted (with N,Ndiethylaminobenzaldehyde as the negative control) to assess aldehyde dehydrogenase (ALDH) activity (a recognized CSC marker), and bulk JJ012, ALDHhigh and PRP1 treated ALDHlow cells were sorted using flow cytometry. Colony formation and spheroid formation assays of cell fractions, including CSCs, were used to compare the PRP1treated groups with the control. CSCs were assessed for early apoptosis and cell death with a modified Annexin V/propidium iodide assay. Western blotting was used to identify mesenchymal stem cell markers (STRO1, CD44 and STAT3), and spheroid selfrenewal assays were also conducted. A clonogenic doseresponse assay demonstrated that 20 µg/ml PRP1 was the most effective dose for reducing colony formation capacity. Furthermore, CSC spheroid growth was significantly reduced with increasing doses of PRP1. Annexin V analysis demonstrated that PRP1 induced CSC cell death, and that this was not attributed to apoptosis or necrosis. Western blot analysis confirmed the expression of mesenchymal markers, and the spheroid selfrenewal assay confirmed the presence of selfrenewing CSCs. The results of the present study demonstrate that PRP1 eliminates anchorage independent CSC growth and spheroid formation, indicating that PRP1 likely inhibits tumor formation in a murine model. Additionally, a decrease in nonCSC bulk tumor cells indicates an advantageous decline in tumor stromal cells. These findings confirm that PRP1 inhibits CSC proliferation in a 3D tumor model which mimics the behavior of chondrosarcoma in vivo.
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Péptidos Catiónicos Antimicrobianos/farmacología , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/metabolismo , Condrosarcoma/metabolismo , Células Madre Neoplásicas/citología , Antígenos de Superficie/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Condrosarcoma/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Humanos , Receptores de Hialuranos/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Factor de Transcripción STAT3/metabolismo , Esferoides Celulares/citología , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismoRESUMEN
Chondrosarcoma is the second most common primary malignant bone tumor and is resistant to chemotherapy and radiation. Inadequate treatment response and poor prognosis requires novel therapeutic approaches. Prolinerich polypeptide1 (PRP1), synthesized by brain neurosecretory cells, has demonstrated antitumor properties in JJ012cells; however, its underlying molecular mechanism remains unclear. The present study aimed to investigate the epigenetic regulation by which PRP1 inhibits chondrosarcoma cancer stem cell (CSC) proliferation and to elucidate additional CSC biomarkers in human chondrosarcoma other than ALDH1A1. Human chondrosarcoma JJ012cells were treated with PRP1 prior to performing an Aldefluor™ assay and fluorescenceactivated cell sorting in order to determine aldehyde dehydrogenase (ALDH) expression levels and isolate ALDHhigh and ALDHlow cell populations. ALDH is an established marker of CSCs in several neoplasms, including chondrosarcoma. The cells were collected and lysed for gel electrophoresis, followed by western blot analysis. The Aldefluor™ assay was used to assess the expression levels of wellestablished CSC biomarkers, including CD133, CD4, CD10, CD144, CD177, CD221, CD271, leucinerich repeatcontaining G proteincoupled receptor 5, SOX2 and B lymphoma MoMLV insertion region 1 homolog (BMI1), within the ALDHhigh population of JJ012 cells. The results confirmed that ALDHA1 was the biomarker for chondrosarcoma CSCs. PRP1 was demonstrated to inhibit the ALDHhigh population colony and sarcosphere formation; 5 µg/ml PRP1 was indicated to be the optimum concentration in eliminating colonies formed by JJ012 cells (92%, P<0.001) and by the ALDHhigh CSCpopulation (80.5%, P<0.001) in the clonogenic doseresponse assay. Spheroid growth unequivocally decreased with an increase in PRP1 dose. In order to determine the molecular mechanism by which PRP1 decreased the CSC population, the regulation of the mammalian Switch/sucrose nonfermenting (SWI/SNF) complex, also referred to as BRG1associated factor (BAF) complex, which either activates or represses transcription, thus acting as an oncogene or tumor suppressor in human cells, was analyzed. PRP1 was demonstrated to decrease the expression levels of BRG, BAF170 and BRM; therefore, in JJ012 cells, these key players of the SWI/SNF (BAF) complex served an oncogenic role. The results of the present study demonstrated that PRP1 targets chromatinremodeling complexes; therefore, future efforts will be directed towards determining the interconnection between CSC maintenance, selfrenewal capacity and BAF complexes.
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Péptidos Catiónicos Antimicrobianos/farmacología , Neoplasias Óseas/metabolismo , Condrosarcoma/metabolismo , Células Madre Neoplásicas/metabolismo , Proteínas Proto-Oncogénicas B-raf/metabolismo , Familia de Aldehído Deshidrogenasa 1/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Condrosarcoma/tratamiento farmacológico , Cromatina/efectos de los fármacos , Cromatina/genética , Epigénesis Genética/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Retinal-Deshidrogenasa/metabolismoRESUMEN
Metastatic chondrosarcoma is a bone malignancy not responsive to conventional therapies; new approaches and therapies are urgently needed. We have previously reported that mTORC1 inhibitor, antitumorigenic cytostatic proline rich polypeptide 1 (PRP-1), galarmin caused a significant upregulation of tumor suppressors including TET1/2 and SOCS3 (known to be involved in inflammatory processes), downregulation of oncoproteins and embryonic stem cell marker miR-302C and its targets Nanog, c-Myc and Bmi-1 in human chondrosarcoma. To understand better the mechanism of PRP-1 action it was very important to identify the receptor it binds to. Nuclear pathway receptor and GPCR assays indicated that PRP-1 receptors are not G protein coupled, neither do they belong to family of nuclear or orphan receptors. In the present study, we have demonstrated that PRP-1 binding interacting partners belong to innate immunity pattern recognition toll like receptors TLR1/2 and TLR6 and gel forming secreted mucin MUC5B. MUC5B was identified as PRP-1 receptor in human chondrosarcoma JJ012 cell line using Ligand-receptor capture technology. Toll like receptors TLR1/2 and TLR6 were identified as binding interaction partners with PRP-1 by western blot analysis in human chondrosarcoma JJ012 cell line lysates. Immunocytochemistry experiments confirmed the finding and indicated the localization of PRP-1 receptors in the tumor nucleus predominantly. TLR1/2, TLR6 and MUC5B were downregulated in human chondrosarcoma and upregulated in dose-response manner upon PRP-1 treatment. Experimental data indicated that in this cellular context the mentioned receptors had tumor suppressive function.