RESUMO
Lung cancer has the highest mortality among all types of cancer; during its development, cells can acquire neural and endocrine properties that affect tumor progression by releasing several factors, some acting as immunomodulators. Neuroendocrine phenotype correlates with invasiveness, metastasis, and low survival rates. This work evaluated the effect of neuroendocrine differentiation of adenocarcinoma on the mouse immune system. A549 cells were treated with FSK (forskolin) and IBMX (3-Isobutyl-1-methylxanthine) for 96 h to induce neuroendocrine differentiation (NED). Systemic effects were assessed by determining changes in circulating cytokines and immune cells of BALB/c mice immunized with PBS, undifferentiated A549 cells, or neuroendocrine A549NED cells. A549 cells increased circulating monocytes, while CD4+CD8- and CD4+CD8+ T cells increased in mice immunized with neuroendocrine cells. IL-2 and IL-10 increased in mice that received untreated A549 cells, suggesting that the immune system mounts a regulated response against adenocarcinoma, which did not occur with A549NED cells. Cocultures demonstrated the cytotoxic capacity of PBMCs when confronted with A549 cells, while in the presence of neuroendocrine cells they not only were unable to show cytolytic activity, but also lost viability. Neuroendocrine differentiation seems to mount less of an immune response when injected in mice, which may contribute to the poor prognosis of cancer patients affected by this pathology.
Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias Pulmonares , Camundongos , Animais , Linfócitos T CD8-Positivos , Neoplasias Pulmonares/patologia , Adenocarcinoma/patologia , Imunidade , Diferenciação CelularRESUMO
Neuroendocrine tumors are part of a heterogeneous group of tumors located in organs such as the gastrointestinal tract (GIT), lungs, thymus, thyroid, and adrenal glands. The most prevalent sites are the small intestine, cecal appendix, and pancreas. More than 50% of these tumors are associated with metastases at the time of diagnosis. Neuroendocrine tumors are classified according to the degree of cell differentiation and the histopathological proliferation index of the lesion. Neuroendocrine tumors can be well differentiated or poorly differentiated. G3 tumors are characterized by Ki-67 expression greater than 20% and can be either well differentiated (G3 NET) or poorly differentiated (G3 NEC). Neuroendocrine carcinoma (NEC G3) is subdivided into small-cell and large-cell types. When neuroendocrine tumors present clinical and compressive symptoms, carcinoid syndrome is evident. Carcinoid syndrome occurs when the tumor produces neuroendocrine mediators that cannot be metabolized by the liver due to either the size of the tumor or their secretion by the liver itself. Several therapeutic strategies have been described for the treatment of metastatic neuroendocrine tumors, including curative or palliative surgical approaches, peptide receptor radionuclide therapy, percutaneous therapy, systemic chemotherapy, and radiotherapy. Liver surgery is the only approach that can offer a cure for metastatic patients. Liver metastases must be completely resected, and in this context, orthotopic liver transplantation has gained prominence for yielding very promising outcomes in selected cases. The aim of this study is to review the literature on OLT as a form of treatment with curative intent for patients with gastroenteropancreatic neuroendocrine tumors with liver metastasis.
RESUMO
The neuroendocrine transdifferentiation has been found in many cancer cell types, such as prostate, lung and gastrointestinal cells and is accompanied by a lower patient life expectancy. The transdifferentiation process has been induced in vitro by the exposure to different stimuli in human lung adenocarcinoma. The aim of this work was to identify the morphological characteristics of the neuroendocrine phenotype in a human lung cancer cell line, induced by two cAMP elevating agents (IBMX and FSK). Our results showed two phenotypes, one produced by IBMX with higher volume, cell size and increased number of secondary projections, and the other produced by FSK with higher area, roughness of the membrane, cell neurite percentage, number of outgrowths per cell and increased number of primary projections. In conclusion, we describe some morphological and ultrastructural characteristics of the neuroendocrine phenotype in A549 human lung cancer cell line promoted by IBMX and FSK to contribute to the understanding of the autocrine or paracrine signaling within the tumor microenvironment.
Assuntos
Adenocarcinoma de Pulmão , Transdiferenciação Celular , Neoplasias Pulmonares , Células A549 , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/ultraestrutura , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/ultraestrutura , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/ultraestruturaRESUMO
Se presenta el caso de una mujer joven, que tuvo varios episodios de sangrado digestivo oscuro manifiesto por lo que requirió soporte transfusional, realización de dos esofagogastroduodenoscopias y dos colonoscopias, en las que no se identificó causa del sangrado. Se realizó enteroscopia de doble balón encontrando una lesión subepitelial, ulcerada, de aspecto neoplásico en el íleon, la cual se marcó con tinta china y se tomaron biopsias que no fueron diagnósticas. Después de realizar estudios de extensión que fueron negativos, se llevó a laparotomía diagnóstica y terapéutica resecando el segmento de ileon comprometido por la lesión y cuyo diagnóstico histopatológico y por inmunohistoquímica fue conclusivo de carcinoma neuroendocrino mal diferenciado de alto grado de célula grande. Al final presentamos además, una revisión de sangrado oscuro manifiesto y tumor neuroendocrino de intestino delgado.
Young woman who is having episodes of overt obscure gastrointestinal bleeding that requires transfusions. The endoscopic study consists of 2 endoscopies of the upper digestive system and two colonoscopies. The tests do not find the cause of the digestive hemorrhage. A double-balloon enteroscopy is performed and it is found that the Ileum has an ulcerate subepitelial lesion with neoplasic appearance which is marked with Chinese ink and biopsies are taken from the tissue which are not diagnosed. Studies of staging are performed ant the result is negative. A laparatomy is performed for diagnosis and treatment which includes the intestinal resection of ileum where the tumor is placed. The result of the test shows to be a neuroendocrine carcinoma of high degree of large cells undifferentiated. One appears in addition a revision to overt obscure gastrointestinal bleeding and neuroendocrine tumor of small bowel.