Asunto(s)
Estenosis Esofágica/diagnóstico , Enfermedades Intestinales/epidemiología , Síndrome de Stevens-Johnson/complicaciones , Adulto , Endoscopía Gastrointestinal , Mucosa Esofágica/diagnóstico por imagen , Mucosa Esofágica/inmunología , Estenosis Esofágica/epidemiología , Estenosis Esofágica/inmunología , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/inmunología , Mucosa Intestinal/diagnóstico por imagen , Mucosa Intestinal/inmunología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome de Stevens-Johnson/inmunologíaRESUMEN
BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS: Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. RESULTS: 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9â years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27â months (0.26-213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). CONCLUSIONS: In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Neoplasias Colorrectales/diagnóstico , Síndromes Neoplásicos Hereditarios/diagnóstico , Proteínas Adaptadoras Transductoras de Señales/genética , Adenosina Trifosfatasas/genética , Adolescente , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Niño , Preescolar , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Enzimas Reparadoras del ADN/genética , Proteínas de Unión al ADN/genética , Femenino , Humanos , Lactante , Masculino , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS/genética , Mutación , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/terapia , Proteínas Nucleares/genética , Resultado del Tratamiento , Adulto JovenRESUMEN
The molecular basis for the resistance of tumor cells to cell-mediated cytotoxicity remains poorly understood and thus poses a major challenge for cancer immunotherapy. The present study was designed to determine whether the WNT1-inducible signaling pathway protein 2 (WISP2, also referred to as CCN5), a key regulator of tumor cell plasticity, interferes with tumor susceptibility to cytotoxic T-lymphocyte (CTL)-mediated lysis. We found that silencing WISP2 signaling in human breast adenocarcinoma MCF7 cells impairs CTL-mediated cell killing by a mechanism involving stem cell marker Kruppel-like factor-4 (KLF-4) induction and microRNA-7 (miR-7) downregulation. Inhibition of transforming growth factor beta (TGF-ß) signaling using the A83-01 inhibitor in MCF7-shWISP2 cells resulted in a significant reversal of the epithelial-to-mesenchymal-transitioned (EMT) phenotype, the expression of KLF-4 and a partial recovery of target susceptibility to CTLs. More importantly, we showed that silencing KLF-4 was accompanied by a reduction in MCF7-shWISP2 resistance to CTLs. Using human breast cancer tissues, we demonstrated the coexpression of KLF-4 with EMT markers and TGF-ß pathway signaling components. More importantly, we found that KLF-4 expression was accompanied by miR-7 inhibition, which is partly responsible for impairing CTL-mediated lysis. Thus, our data indicate that WISP2 has a role in regulating tumor cell susceptibility through EMT by inducing the TGF-ß signaling pathway, KLF-4 expression and miR-7 inhibition. These studies indicate for the first time that WISP2 acts as an activator of CTL-induced killing and suggests that the loss of its function promotes evasion of immunosurveillance and the ensuing progression of the tumor.
Asunto(s)
Neoplasias de la Mama/inmunología , Proteínas CCN de Señalización Intercelular/inmunología , Regulación Neoplásica de la Expresión Génica/inmunología , Inmunidad Celular , Factores de Transcripción de Tipo Kruppel/inmunología , MicroARNs/inmunología , ARN Neoplásico/inmunología , Proteínas Represoras/inmunología , Linfocitos T/inmunología , Neoplasias de la Mama/patología , Proteínas CCN de Señalización Intercelular/genética , Línea Celular Tumoral , Femenino , Humanos , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , MicroARNs/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/inmunología , ARN Neoplásico/genética , Proteínas Represoras/genética , Linfocitos T/patología , Vía de Señalización WntRESUMEN
Uterine lipomas are uncommon. Several histology hypotheses are described. Ultrasound is firstly performed but diagnosis is sometimes difficult. Magnetic resonance imaging is more specific and helpful to make a differential diagnosis with a dermoid ovarian cyst. Despite those imaging exams we detail a case of a patient where a laparoscopic hysterectomy with bilateral salpingo-oophorectomy and preliminary adhesiolysis has been necessary to establish diagnosis. Among her medical history some previous abdominal surgeries could be the cause of this lesion.
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Laparotomía/efectos adversos , Lipoma/etiología , Neoplasias Uterinas/etiología , Anciano , Femenino , Humanos , Lipoma/diagnóstico , Neoplasias Uterinas/diagnósticoRESUMEN
In most cases, fibrolamellar hepatocellular carcinoma has specific and distinctive histopathological features that distinguish it from hepatocellular carcinoma. Magnetic resonance imaging can provide characteristic features to obtain a diagnosis of this entity. We report a case of fibrolamellar hepatocellular carcinoma with a radiological-pathological correlation in a 37 year-old man with chronic viral hepatitis B without cirrhosis who underwent right hepatectomy.
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Carcinoma Hepatocelular/etiología , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/etiología , Adulto , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , MasculinoRESUMEN
Pulmonary artery sarcoma is a rare tumor. We present a case of intimal sarcoma arising from right pulmonary artery and left lower pulmonary vein observed in a 44-year-old man with a non-productive cough. Computed tomographic scans and magnetic resonance imaging showing filling defect enhancement contributed early, suggesting the diagnosis of primary vascular tumor, hypothesis confirmed by pathologist findings.