ABSTRACT
Transactivation of receptor tyrosine kinases (RTK) is a crosstalk mechanism exhibited by G-protein-coupled receptors (GPCR) to activate signaling pathways classically associated with growth factors. The discovery of RTK transactivation was a breakthrough in signal transduction that contributed to developing current concepts in intracellular signaling. RTK transactivation links GPCR signaling to important cellular processes, such as cell proliferation and differentiation, and explains the functional diversity of these receptors. Purinergic (P2Y and adenosine) receptors belong to class A of GPCR; in the present work, we systematically review the experimental evidence showing that purinergic receptors have the ability to transactivate RTK in multiple tissues and physiopathological conditions resulting in the modulation of cellular physiology. Of particular relevance, the crosstalk between purinergic receptors and epidermal growth factor receptor is a redundant pathway that participates in multiple pathophysiological processes. Specific and detailed knowledge of purinergic receptor-regulated pathways advances our understanding of the complexity of GPCR signal transduction and opens the way for pharmacologic intervention in the pathological context.
ABSTRACT
Cancer comprises a collection of diseases that occur in almost any tissue and it is characterized by an abnormal and uncontrolled cell growth that results in tumor formation and propagation to other tissues, causing tissue and organ malfunction and death. Despite the undeniable improvement in cancer diagnostics and therapy, there is an urgent need for new therapeutic and preventive strategies with improved efficacy and fewer side effects. In this context, purinergic signaling emerges as an interesting candidate as a cancer biomarker or therapeutic target. There is abundant evidence that tumor cells have significant changes in the expression of purinergic receptors, which comprise the G-protein coupled P2Y and AdoR families of receptors and the ligand-gated ion channel P2X receptors. Tumor cells also exhibit changes in the expression of nucleotidases and other enzymes involved in nucleotide metabolism, and the concentrations of extracellular nucleotides are significantly higher than those observed in normal cells. In this review, we will focus on the potential role of purinergic signaling in the ten most lethal cancers (lung, breast, colorectal, liver, stomach, prostate, cervical, esophagus, pancreas, and ovary), which together are responsible for more than 5 million annual deaths.
Subject(s)
Adenosine Triphosphate/metabolism , Autocrine Communication/physiology , Neoplasms/metabolism , Paracrine Communication/physiology , Receptors, Purinergic/metabolism , Adenosine Triphosphate/genetics , Animals , Humans , Neoplasms/genetics , Neoplasms/mortality , Receptors, Purinergic/genetics , Signal Transduction/physiologyABSTRACT
We report a 48 years old women presenting with a painful abdominal mass and hepatomegaly. An abdominal CAT scan showed a focal lesion of 14 cm diameter in liver segment 4. The patient was subjected to a left hepatectomy with a normal postoperative evolution. The pathological diagnosis of the surgical piece was an undifferentiated sarcoma. Nine months later, a local relapse was detected and the patient died 22 months after the operation.
Introducción: Los sarcomas indiferenciados (embrionario) del hígado (SIEH) son neoplasias infrecuentes. Se presentan principalmente en edad pediátrica y son considerados de mal pronóstico. En adultos, existen 71 pacientes publicados en el mundo, y en nuestro país no hay casos descritos en este grupo etario. Objetivos: Presentar el caso de una paciente adulta portadora de un SIEH, que fue sometida a cirugía resectiva y realizar una revisión del tema. Caso clínico: Mujer de 48 años de edad, con historia de dolor abdominal, masa palpable en epigastrio y hepatomegalia. Marcadores tumorales negativos, tomografía abdominal revela lesión focal de 14 centímetros en segmento 4. Se aborda quirúrgicamente, biopsia rápida revela tumor sólido maligno indiferenciado, y se realiza hepatectomía izquierda. Evolución postoperatoria favorable. Mediante el análisis histopatológico, histoquímico e inmunohistoquímico se diagnostica un SIEH y se corrobora una resección R0. Al noveno mes de evolución se pesquisa foco de recidiva hepática, inicia progresivo compromiso del estado general, falleciendo 22 meses después de la cirugía. Discusión: Actualmente se recomienda resección completa del tumor seguido de quimioterapia coadyuvante, con lo cual se han logrado sobrevidas libres de enfermedad mayores a 5 años. El dar a conocer las experiencias de casos aislados en esta patología tan infrecuente, permitiría aumentar la casuística mundial, mejorar las técnicas de enfrentamiento, y evaluar el impacto de la quimioterapia en el pronóstico.
Subject(s)
Humans , Female , Adult , Hepatectomy , Liver Neoplasms/surgery , Neoplasms, Germ Cell and Embryonal/surgery , Chemotherapy, Adjuvant , Fatal Outcome , Neoplasm Recurrence, Local , Liver Neoplasms/pathology , Liver Neoplasms/drug therapy , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/drug therapy , SarcomaABSTRACT
Se revisan, en forma retrospectiva, 16 pacientes con lesiones iatrogénicas de la vía biliar atendidos en el Hospital San Pablo de Coquimbo entre los años 1981 y 2004. Doce de estas lesiones ocurrieron en el Hospital de Coquimbo y 4 pacientes fueron derivados desde otros hospitales. 10 casos ocurrieron durante cirugía abierta y 6 en cirugía laparoscópica. La mitad de las lesiones fueron detectadas durante la intervención (8 casos). Las reparaciones inmediatas fueron anastomosis ductal primaria en 3 casos, todos con malos resultados. En 5 casos se realizó hepático yeyunoanastomosis (HYA) inmediata con evolución favorable a largo plazo. De los 8 pacientes con diagnóstico postoperatorio se repararon 6 con HYA de los cuales uno evolucionó con estenosis; una lesión menor con coledocorrafia y sonda T y otro paciente con el retiro de los clips de la vía biliar. En 8 de las 13 HYA se utilizó el asa de Hutson Russell para la reconstrucción. En 2 casos con estenosis posterior, se utilizó el asa para la dilatación endoscópica percutánea. El manejo quirúrgico de las lesiones iatrogénicas de la vía biliar ha sido exitoso en la gran mayoría de los casos (81,3%). Fallece un enfermo (6,3%) con lesión combinada vascular y canalicular, confirmando la gravedad y mal pronóstico de estas lesiones. Recomendamos el asa de Hutson Russell para la reconstruccción, pues en 2 pacientes nos permitió solucionar la estenosis posterior a la reparación quirúrgica mediante dilatación endoscópica percutánea evitando nuevas cirugías derivativas.
Background: Biliary tract lesions occur in 0.3% of all cholecystectomies and are the most feared complications of this procedure. Aim: To report the experience in the management of iatrogenic biliary tract lesions. Material and Methods: Retrospective study of 16 patients with iatrogenic bile duct injuries treated at a Chilean Regional Hospital between 1981 and 2004. Results: Twelve injuries occurred in the same hospital and four were referred from elsewhere. Ten injuries occurred during open and six, during laparoscopic surgery. Eight injuries were detected during the operation. In three occasions an immediate primary ductal anastomosis was attempted, but the procedure failed in every case. Five cases were repaired with bilio-jejuno anastomosis, with a good outcome in all. Six of the eight patients whose lesion was detected in the postoperative period, were reconstructed with a bilio-jejuno anastomosis and one developed to postoperative stricture. One patient with a minor injury, was treated with suture of the choledochus and T tube placement. Other patient only required the extraction of titanium clips, as treatment. In eight of the 13 bilio-jejuno anastomoses, the Hutson Russell loop was used for the reconstruction. In 2 cases that developed a postoperative stricture, this loop was used for percutaneous endoscopic dilatation. The surgical management was successful in 81% of patients. One patient, who had a combined vascular and ductal injury, died. Conclusions: We recommend the use of Hutson Russell loop for biliary reconstruction, because it allowed us to perform an endoscopic dilatation in two cases, avoiding new surgical procedures.
ABSTRACT
Se estudia en forma prospectiva y randomizada, el uso de drenajes en 43 pacientes portadores de peritonitis apendicular. Se realiza el mismo procedimiento en cuanto a técnica quirúrgica, lavado peritoneal y terapia antibiótica. Los pacientes son asignados a los grupos con y sin drenaje mediante sorteo. Ambos grupos son estadísticamente comparables. Se observó un 16% de complicaciones en el grupo sin drenaje y 22,2% en el grupo con drenaje. No hay diferencias significativas en la morbilidad de ambos grupos. No hubo mortalidad en la serie. Se concluye que el uso de drenajes no es relevante en el tratamiento de la peritonitis apendicular
