RESUMEN
BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare peritoneal mucinous carcinomatosis with largely unknown underlying molecular mechanisms. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the only therapeutic option; however, despite its use, recurrence with a fatal outcome is common. The lack of molecular characterisation of PMP and other mucinous tumours is mainly due to the physicochemical properties of mucin. RESULTS: This manuscript describes the first protocol capable of breaking the mucin barrier and isolating proteins from mucinous tumours. Briefly, mucinous tumour samples were homogenised and subjected to liquid chromatography using two specific columns to reduce mainly glycoproteins, albumins and immunoglobulin G. The protein fractions were then subjected to mass spectrometry analysis and the proteomic profile obtained was analysed using various bioinformatic tools. Thus, we present here the first proteome analysed in PMP and identified a distinct mucin isoform profile in soft compared to hard mucin tumour tissues as well as key biological processes/pathways altered in mucinous tumours. Importantly, this protocol also allowed us to identify MUC13 as a potential tumour cell marker in PMP. CONCLUSIONS: In sum, our results demonstrate that this protein isolation protocol from mucin will have a high impact, allowing the oncology research community to more rapidly advance in the knowledge of PMP and other mucinous neoplasms, as well as develop new and effective therapeutic strategies.
RESUMEN
Pseudomyxoma peritonei (PMP) is a rare disease characterized by a massive accumulation of mucus in the peritoneal cavity. The only effective treatment is aggressive surgery, aimed at removing all visible tumors. However, a high percentage of patients relapse, with subsequent progression and death. Recently, there has been an increase in therapies that target mutated oncogenic proteins. In this sense, KRAS has been reported to be highly mutated in PMP, with KRASG12D being the most common subtype. Here, we tested the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in a high-grade PMP xenograft mouse model carrying a KRASG12D mutation. The results obtained in this work showed a profound inhibition of tumor growth, which was associated with a reduction in cell proliferation, an increase in apoptosis, and a reduction in the MAPK and PI3K/AKT/mTOR signaling pathways. In conclusion, these results demonstrate the high potency and efficacy of MRTX1133 in KRASG12D-PMP tumors and provide a rationale for clinical trials.
RESUMEN
Introducción: Un número importante de pacientes que ingresan al programa de diálisis peritoneal reciben simultáneamente la noticia de que tienen enfermedad renal crónica en etapa terminal y requieren diálisis peritoneal. Para muchos de ellos la noticia es inesperada y desconsoladora, ya que tienen que acceder a la diálisis para poder seguir viviendo.Material y Método: Estudio cualitativo, descriptivo con enfoque fenomenológico. De 106 pacientes incidentes del programa de diálisis peritoneal ambulatoria a quienes se les solicitó consentimiento informado para contestar el instrumento (Coping Inventory Strategies), se seleccionaron 14 pacientes que relataron sus vivencias respecto a su diagnóstico de enfermedad renal crónica y la necesidad urgente de diálisis peritoneal. Se les pidió que escribieran en una cuartilla cómo enfrentaron la noticia de insuficiencia renal crónica y requerir diálisis peritoneal.Resultados: Se incluyeron en el estudio a 14 pacientes, con edad comprendida entre 41 y 61 años, y el 66% fueron mujeres. Se identificaron tres categorías y siete subcategorías: sociolaboral (estigma social e incertidumbre por el trabajo); actitud ante la muerte (resignación y sentimiento de culpa) y acompañamiento familiar (toma de decisiones, motivación y apoyo). El mayor número de pacientes se ubicó en la categoría de actitud ante la muerte y en la subcategoría de resignación como estrategia de afrontamiento.Conclusiones: Los pacientes describieron la fase en la que se enteraron de su diagnóstico y el ingreso a diálisis peritoneal como el momento más difícil y traumático, manifestaron sentimientos de angustia, limitaciones personales o sociales y reconocieron la dependencia del apoyo familiar. (AU)
Introduction: A significant number of patients starting on peritoneal dialysis are simultaneously told that they have end-stage chronic kidney disease and require peritoneal dialysis. For many patients the news is unexpected and heartbreaking, as they have to access dialysis in order to stay alive.Method: Qualitative, descriptive study with a phenomenological approach. Of the 106 patients who were admitted to the outpatient peritoneal dialysis program, and who were asked for informed consent to answer the (Coping Inventory Strategies) instrument, 14 patients were selected who expressed their experiences regarding the diagnosis of chronic kidney disease and the urgent need for peritoneal dialysis. They were asked to write in one page how they coped with the news of chronic renal failure and the need for peritoneal dialysis.Results: The mean age was 58.3 years, 66% female and 34% male. Three categories and seven subcategories were identified: socio-occupational (social stigma and uncertainty about the work situation); attitude to death (resignation and guilt) and family support (decision-making, motivation and support). The highest number of patients fell into the category of attitude to death and the subcategory of resignation as a coping strategy.Conclusions: Patients described the phase when they learned of their diagnosis and admission to peritoneal dialysis as the most difficult and traumatic time, expressed feelings of distress, personal or social limitations and confessed dependence on family support. (AU)