RESUMEN
Glucocorticoid receptor (GR) modulates extensive biological and pathological processes including tumor progression through diverse mechanisms. The regulatory effects of dexamethasone (DEX), a synthetic glucocorticoid, as well as its interaction with GR have been recognized beyond hematologic cancers. In the present study, we investigated the anti-cancer efficacy of DEX and the correlation with GR in pancreatic cancer, a most aggressive malignancy threatening human health. The differential levels of GR expression were examined in two human pancreatic cancer cell lines, PANC-1 and SW1990, as well as in xenografts and patient tumor tissues. DEX significantly inhibited colony formation, migration, and tumor growth of PANC-1 cells expressing abundant GR. The underlying mechanisms involved suppression of nuclear factor κB (NF-κB) phosphorylation and down-regulation of epithelial-to-mesenchymal transition (EMT), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF). The anti-cancer effects of DEX were partially reversed by GR silencing or combinational administration of GR antagonist, RU486. The dose-dependent efficacy of DEX in tumor growth inhibition was also demonstrated in a GR-positive patient-derived xenograft model along with safety in mice. DEX was less potent, however, in SW1990 cells with poor GR expression. Our findings suggest that DEX effectively inhibits pancreatic tumor growth partially through GR activation. The potential correlation between GR expression and anti-cancer efficacy of DEX may have some clinical implications.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Dexametasona/uso terapéutico , Neoplasias Pancreáticas/metabolismo , Receptores de Glucocorticoides/metabolismo , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Células A549 , Animales , Antineoplásicos Hormonales/farmacología , Dexametasona/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Glucocorticoides/farmacología , Glucocorticoides/uso terapéutico , Humanos , Células MCF-7 , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Pancreáticas/tratamiento farmacológico , Carga Tumoral/fisiologíaRESUMEN
RATIONALE: stiff limb syndrome (SLS) is a variant of stiff-man syndrome, primarily affecting a specific limb. Its diagnosis has always been challenging due to the lack of a specific confirmation test. We present a rare case of a patient with lower limb myoclonus and rigidity. PATIENT CONCERNS: A 53-year-old male presented with a sudden onset of progressive left lower extremity myoclonus and muscle rigidity for 3 days. He rapidly showed signs of right lower limb involvement with severe joint stiffness and inability to walk. DIAGNOSIS: The symptoms nature, physical examination, careful elimination of differential diagnosis suggested a diagnosis of stiff limb syndrome. INTERVENTIONS: Intravenous infusion of gamma globulin 0.4âmg/kg coupled with baclofen and clonazepam were given after admission. He also received an injection of botulinum toxin A to relieve his muscle stiffness. OUTCOMES: The patients' condition improved after the initial treatment with complete disappearance of muscle twitching. Further improvements were seen later on after the local administration of botulinum toxin A. LESSONS: Stiff limb syndrome shares the same complex symptoms with many other conditions. Its diagnosis relies heavily on clinical presentations and on ruling out other conditions. However, unusual symptoms such as myoclonus can occur in few cases and together with the rarity of the condition, the prevalence of misdiagnosis is high. Therefore, being aware and recognizing the signs and symptoms is crucial for proper management. Additionally, EMG is a very important test if the present condition is suspected. However, a negative EMG result or a negative anti-glutamic acid decarboxylase antibody test should not exclude SLS diagnosis.
Asunto(s)
Rigidez Muscular/etiología , Mioclonía/etiología , Síndrome de la Persona Rígida/complicaciones , Síndrome de la Persona Rígida/fisiopatología , Baclofeno/uso terapéutico , Toxinas Botulínicas Tipo A/uso terapéutico , Diagnóstico Diferencial , Electromiografía , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Extremidad Inferior , Masculino , Persona de Mediana Edad , Rigidez Muscular/fisiopatología , Mioclonía/fisiopatología , Síndrome de la Persona Rígida/diagnóstico , Síndrome de la Persona Rígida/tratamiento farmacológicoRESUMEN
BACKGROUND: In China, cervical cancer is the fifth most commonly diagnosed cancer, and the outcomes for patients with advanced or recurrent disease are poor. Apatinib, a small molecule inhibitor of vascular endothelial growth factor receptor (VEGFR-2), is an orally bioavailable agent, which has shown survival benefit in multiple solid tumors. Based on previous research, this phase II clinical trial aims to verify apatinib's efficacy and safety in patients with advanced or recurrent cervical cancer. METHODS/DESIGN: This randomized, parallel arm, open-label, interventional trial will be carried out to evaluate the efficacy and the safety of apatinib for advanced or recurrent cervical cancer. A total of 60 eligible patients will be allocated by intention, in a ratio of 1:1, to either the experimental group or the control group. The primary endpoint is progression-free survival, the secondary endpoints include overall survival, disease control rate, objective response rate, quality of life, and adverse events. Assessments will be carried out before enrolment (baseline) and every 4 weeks after treatment. DISCUSSION: The aim of this trial is to demonstrate the clinical effect, safety, and side effects of apatinib in the treatment of advanced or recurrent cervical cancer. This study will clarify the efficacy and safety of this regimen. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR-OIN-17012164 . Registered on 24 July 2017.