Biomedical subjects

Jorge Cuevas

Publications and source records attributed to Jorge Cuevas.

4 recordsLinked to original sources

PubMed2005

Blockade of epidermal growth factor receptors chemosensitizes breast cancer cells through up-regulation of Bnip3L.

Epidermal growth factor receptor-1 (EGFR) and EGFR-2 (HER2) have become major targets for cancer treatment. Blocking antibodies and small-molecule inhibitors are being used to silence the activity of these receptors in different tumors with varying efficacy. Thus, a better knowledge on the signaling pathways activated by EGFR and HER2 may help unravel novel therapeutic targets and molecular markers of response. Here, we show that treatment of breast cancer cell lines with blocking antibodies against EGFR (cetuximab) or HER2 (trastuzumab) promotes the specific induction of proapoptotic Bnip3L and chemosensitization. Moreover, we found that the Bnip3L gene is transcriptionally activated by FoxO3a. Trastuzumab-mediated induction of Bnip3L and nuclear translocation of FoxO3a was also shown in pleural effusion cells from a breast cancer patient. Transfection of breast cancer cells with constitutively active FoxO3a or with Bnip3L promotes sensitization to chemotherapy-induced apoptosis. On the contrary, blockade of Bnip3L expression by a small interfering RNA strategy significantly diminished the chemosensitizing effect of cetuximab. We found also an inverse correlation between EGFR and Bnip3L expression in surgical specimens from patients with breast cancer. Therefore, blockading EGFR or HER2 specifically up-regulates Bnip3L, which is required for chemosensitization of breast cancer cells. This novel pathway provides also the rationale for therapeutic strategies aimed to induce the expression of Bnip3L.

Adult↗

PubMed2005

Cerebral scedosporiosis: an emerging fungal infection in severe neutropenic patients: CT features and CT pathologic correlation.

Scedosporium prolificans is an emerging opportunistic fungal agent encountered in severely neutropenic patients. The purpose of this paper is to describe the main cranial CT findings from a retrospective review of six patients (four men and two women, 18-66 years old) afflicted with disseminated infection by S. prolificans with neurological symptoms. They were severely neutropenic and presented with severe respiratory failure and conscience deterioration, with a subsequent 100% mortality. The final diagnosis was established by autopsy (performed in five patients) and blood culture findings. Cranial CT showed multiple low-density lesions in four patients without contrast enhancement located in the basal ganglia and corticomedullary junction. Autopsy findings of these lesions demonstrated necrosis and hyphae proliferation inside brain infarcts. Also, two of the patients had a subarachnoid hemorrhage, but angiography could not be performed. CT and autopsy findings were fairly similar to those encountered in cerebral aspergillosis; however, possibly because of its rapid and fatal evolution, no edema or ring enhancing lesions were encountered. Thus, Scedosporium can be included as a rare but possible cause of invasive fungal disseminated central nervous system infections in severely neutropenic patients.

Adolescent↗

PubMed2005

Recurrence of bronchioloalveolar carcinoma in donor lung after lung transplantation: microsatellite analysis demonstrates a recipient origin.

Bronchioloalveolar carcinoma is a distinctive subtype of pulmonary adenocarcinoma, without effective therapy, although there have recently been some attempts to use lung transplantation. However, a high post-transplantation local recurrence rate is described with some controversy regarding the possible involved mechanisms, the main possibilities being the lymphatic spread and aerosolization. Presented herein is a case of a bilateral lung transplantation for a bilateral and pneumonic form of non-mucinous bronchioloalveolar carcinoma in a 43-year-old woman. The histological analysis of mediastinal lymph nodes during surgery did not show neoplastic cells. Thirty-five months after transplantation several nodular opacities in donor lungs were detected. Three pulmonary wedge resections were performed showing a non-mucinous bronchioloalveolar carcinoma with the same histological characteristics as the primary. Again, the mediastinal lymph nodes were tumor free. A complete microsatellites molecular analysis was performed to compare the primary and recurrent carcinoma using capillary electrophoresis, showing that the recurrent tumor was generated in a recipient cellular clone. The absence of lymph node metastasis and the molecular evidence of the recipient origin of the neoplasm supports the contamination of the new lungs at the time of implantation as being the reason for the high incidence of recurrence after lung transplantation in this kind of disease.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2003

Primary purely intradermal pleomorphic liposarcoma.

INTRODUCTION: Pleomorphic liposarcoma (PLPS) is a high-grade pleomorphic sarcoma, containing multivacuolated lipoblasts, which usually develops during late adult life. It usually occurs in the deep soft tissues and uncommonly arises in the subcutis, the dermis representing an exceedingly rare site of occurrence. METHODS: We describe a case of PLPS arising in the dorsal aspect of the nose of a 75-year-old woman. Preoperative duration was 9 months. RESULTS: The lesion was intradermal well-circumscribed, dome-shaped, measuring 1.2 cm. It fulfilled the histologic criteria for inclusion in the PLPS category. The tumor cells focally expressed calretinin. A review of the literature yielded four cases documented, to which we add the present report. All the patients were adults with a mean age of 67 (range 39-95) years, and three of five cases arose on the scalp. Local recurrence occurred in one patient, but no distant metastases or disease-related deaths were observed. CONCLUSION: PLPS very rarely arises in the dermis. In spite of high-grade morphology, the intradermal tumor shows a relatively favorable prognosis. Diagnostic consideration includes pleomorphic lipoma, clear cell atypical fibroxanthoma, balloon cell melanoma, and metastatic clear cell carcinoma of renal origin. Recognition of this distinctive and rare type of liposarcoma is essential to avoid under- or misdiagnosis and inappropriate treatment.

Aged↗