Browsing by Author "Gonzalez, Sergio"

Now showing 1 - 10 of 10
  • Thumbnail Image
    Item
    Comparative analysis of loss of heterozygosity and microsatellite instability in adult and pediatric melanoma.
    (2005) Uribe González, Pablo Francisco; Wistuba, Ignacio I.; Solar, Antonieta; Balestrini, Claudia; Perez-Cotapos, Maria Luisa; Gonzalez, Sergio
    Although 0.3% of melanomas occur in children, the incidence has risen in past decades. In adult melanoma, some chromosomal regions in 1p, 6q, 9p, 10q, and 11q are frequently deleted. Microsatellite instability (MSI), which reflects impaired DNA repair, has been found at low levels in adult melanoma and melanocytic nevi. To investigate the molecular changes in pediatric melanoma, a screening for loss of heterozygosity and microsatellite instability was performed and compared with changes found in adult melanoma. Formalin-fixed, paraffin-embedded tissues from 10 adult melanomas, 9 melanocytic nevi, and 8 pediatric melanomas were microdissected and the DNA was extracted. Loss of heterozygosity and microsatellite instability were evaluated using 13 microsatellite repeat polymorphisms located in 1p36, 1q32, 2p12, 2p22-25, 2q33-37, 9p21, 10q23.3, 11q23, 13q14, 17p13, and 17q21. The overall frequency of loss of heterozygosity was 0.09 for nevi, 0.30 for adult melanoma, and 0.43 for pediatric melanoma (nevi vs. adult melanoma, P = 0.0082; nevi vs. pediatric melanoma, P = 0.0092). Pediatric melanoma has more loss of heterozygosity (44%) in 11q23 than adult melanoma (7%, P = 0.046). The microsatellite instability overall frequency was greater in pediatric melanoma (0.24) than nevi (0.05, P = 0.0031) and adult melanoma (0.09, P = 0.0195). Our findings suggest that pediatric melanoma has a different abnormal pattern than adult melanoma. Pediatric melanoma has more microsatellite instability than adult melanoma. 11q23 could contain genes related to the early age onset of melanoma. The high frequency of microsatellite instability is coincidental with the finding of higher levels of microsatellite instability in pediatric brain tumors and could play a role in the pathogenesis of pediatric melanoma.
  • No Thumbnail Available
    Item
    Cutaneous inflammation as a marker of malignant transformation in a patient with linear unilateral basaloid follicular hamartoma
    (2019) Del Barrio-Diaz, Pablo; Meza-Romero, Rodrigo; Gonzalez, Sergio; Vera-Kellet, Cristian
    Basaloid follicular hamartoma is a rare, benign and superficial malformation of hair follicles, characterized histologically by epithelial proliferation of basaloid cells with radial disposition. It can be mistaken for basal cell carcinoma. Even though these hamartomas are considered benign lesions, malignant transformation has rarely been reported. We report the case of a 45-year-old healthy woman, with linear, unilateral basaloid follicular hamartoma which developed inflamed papules histologically suggestive of basal cell carcinoma. We believe that identification of local inflammation could be a clinical clue to guide us towards a malignant transformation of basaloid follicular hamartoma.
  • No Thumbnail Available
    Item
    Differential expression of programmed cell death ligand 1 (PD-L1) and inflammatory cells in basal cell carcinoma subtypes
    (2022) Gompertz-Mattar, Matias; Perales, Juan; Sahu, Aditi; Mondaca, Sebastian; Gonzalez, Sergio; Uribe, Pablo; Navarrete-Dechent, Cristian
    Few studies have evaluated programmed cell death ligand (PD-L1) expression and lymphocytic infiltrates in Basal Cell Carcinoma (BCC). The objectives of this study are to assess PD-L1 expression and markers of local immune response in nodular, superficial, and morpheaform BCC, and compare it to normal, sun-exposed skin from the periphery of intradermal nevi. This was a retrospective study that included three histological subtypes of BCCs, and sun-exposed skin from the periphery of dermal nevi as quality controls. Tissue microarrays (TMA) were constructed with subsequent staining of H&E and immunohistochemistry (IHC) for CD4, CD8, FOXP3 and PD-L1. Non-automated quantification of the infiltrate in the intratumoral and stromal compartments on TMAs was performed. A total of 115 BCC (39 nodular, 39 morpheaform, and 37 superficial) and 41 sun-exposed skin samples were included (mean age 65.4 years; 52.6% females). BCC showed higher expression of PD-L1 (5.4 vs 0.7%, p < 0.001), CD8 (29.8 vs 19.7%, p = 0.002), and FOXP3 (0.3 vs 0.06%, p = 0.022) compared to sun-exposed skin. There was a higher PD-L1 expression in nodular BCC compared with other subtypes. Low-risk BCC subtypes (superficial and nodular) exhibited more PD-L1 expression in intratumoral and stromal immune infiltrates as compared to high-risk BCC subtypes. As a limitation, no immune cells function was evaluated in this study, only the presence/absence of T-lymphocyte sub-populations was recorded. Substantial differences in both PD-L1 expression and lymphocytic infiltrates were found amongst the histological subtypes of BCC and sun-exposed skin. Highest PD-L1 expression was found in nodular BCCs which suggests a potentially targetable strategy in the treatment of this most common BCC subtype.
  • No Thumbnail Available
    Item
    Evidence of autophagic vesicles in a patient with Lisch corneal dystrophy
    (2020) Grau, Arturo E.; Gonzalez, Sergio; Zoroquiain, Pablo; Gonzalez, Pablo A.; Khaliliyeh, Daniela; Morselli, Eugenia; Cortes, Dennis
    Lisch corneal dystrophy is a rare corneal disease characterized by the distinctive feature of highly vacuolated cells. Although this feature is important, the nature of these vacuoles within corneal cells remains unknown. Here, we sought to analyze corneal cells from a patient diagnosed with Lisch dystrophy to characterize the vacuoles within these cells. Analyses using histopathology examination, confocal microscopy, and transmission electron microscopy were all consistent with previous descriptions of Lisch cells. Importantly, the vacuoles within these cells appeared to be autophagosomes and autolysosomes, and could be stained with an anti-microtubule-associated protein 1A/1B-light chain 3 (LC3) antibody. Taken together, these findings indicate that the vacuoles we observed within superficial corneal cells of a patient with Lisch corneal dystrophy constituted autophagosomes and autolysosomes; this finding has not been previously reported and suggests a need for further analyses to define the role of autophagy in this ocular disease.
  • No Thumbnail Available
    Item
    Influence of socioeconomic status on clinical outcomes of malignant melanoma in Chile: A cross-sectional study
    (2015) Molgó Novell, Montserrat; Andino Navarrete, Romina; Silva, Maria Jesus; Navajas Galimany, Lucas; Sazunic, Ivo; Gonzalez, Sergio
  • Thumbnail Image
    Item
    Lack of association between BRAF mutation and MAPK ERK activation in melanocytic nevi
    (NATURE PUBLISHING GROUP, 2006) Uribe, Pablo; Andrade, Leonardo; Gonzalez, Sergio
    The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase signaling pathway can be activated through mutations of V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) oncogene, frequently found in melanoma (60%), common nevi (CN) (73-82%), and atypical nevi (AN) (52-80%). MAPK activation has been reported between 0 and 22% in nevi, and 86% of primary melanoma, without any knowledge of BRAF mutational status. We studied the correlation of MAPK activation status, BRAF mutation, and B-Raf expression in CN, AN, and melanoma. Using immunohistochemistry, phosphorylated (active) MAPK and B-Raf expression was studied in 24 CN, 21 AN, and 26 primary cutaneous melanomas (PM). BRAF mutations at codon 600 were assessed by PCR-RFLP. Active MAPK was detected in 29% of CN, 48% of AN, and 85% of PM. BRAF mutation was found in 67% of CN, 62% of AN, and 58% of PM. In all, 23% of CN, 54% of AN, and 93% of PM with BRAF mutation have activated MAPK. All lesions expressed B-Raf. BRAF mutation does not seem to be sufficient to produce MAPK activation in melanocytic nevi, and it is suggested that other events are needed to induce MAPK activation, that is, B-Raf overexpression, inhibition of MAPK phosphatases, or suppression of RAF kinase inhibitors.
  • Thumbnail Image
    Item
    Leukocytoclastic Vasculitis as Early Manifestation of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma of the Elderly
    (LIPPINCOTT WILLIAMS & WILKINS, 2012) Zoroquiain, Pablo; Gonzalez, Sergio; Molgo, Montserrat; Rodriguez, Alejandra; Valbuena, Jose R.
    Extensive necrotizing vasculitis (ENV) is a rare paraneoplastic phenomenon, and the majority of cases reported are associated with hematolymphoid neoplasms. Histologically, most cases of ENV represent leukocytoclastic vasculitis (LCV). Here we report the clinicopahological features of a 68-year-old man with ENV associated to a Epstein Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) of the elderly, a newly recognized lymphoproliferative disorder, most likely representing a paraneoplastic manifestation. The patient was treated with standard chemotherapy regimen for malignant lymphoma. Due to the extensive involvement of the extremities by ENV, surgical debridement was not feasible and a novel therapy based on CHITOSAN apposits was initiated with overall good response and subsequent re-epithelization of the skin lesions. The patient died of sepsis secondary to a Pseudomona pneumonia 17 months after diagnosis.
  • Thumbnail Image
    Item
    Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-alpha
    (WILEY-BLACKWELL, 2008) Fernandez, Ricardo; Gonzalez, Sergio; Rey, Sergio; Cortes, Paula P.; Maisey, Kevin R.; Reyes, Edison Pablo; Larrain, Carolina; Zapata, Patricio
    In the absence of information on functional manifestations of carotid body (CB) inflammation, we studied an experimental model in which lipopolysaccharide (LPS) administration to pentobarbitone-anaesthetized cats was performed by topical application upon the CB surface or by intravenous infusion (endotoxaemia). The latter caused: (i) disorganization of CB glomoids, increased connective tissue, and rapid recruitment of polymorphonuclear cells into the vascular bed and parenchyma within 4 h; (ii) increased respiratory frequency and diminished ventilatory chemoreflex responses to brief hypoxia (breathing 100% N-2 for 10 s) and diminished ventilatory chemosensory drive (assessed by 100% O-2 tests) during normoxia and hypoxia; (iii) tachycardia, increased haematocrit and systemic hypotension in response to LPS I.V.; and (iv) increased basal frequency of carotid chemosensory discharges during normoxia, but no change in maximal chemoreceptor responses to brief hypoxic exposures. Lipopolysaccharide-induced tachypnoea was prevented by prior bilateral carotid neurotomy. Apoptosis was not observed in CBs from cats subjected to endotoxaemia. Searching for pro-inflammatory mediators, tumour necrosis factor-alpha (TNF-alpha) was localized by immunohistochemistry in glomus and endothelial cells; reverse transcriptase-polymerase chain reaction revealed that the CB expresses the mRNAs for both type-1 (TNF-R1) and type-2 TNF-alpha receptors (TNF-R2); Western blot confirmed a band of the size expected for TNF-R1; and histochemistry showed the presence of TNF-R1 in glomus cells and of TNF-R2 in endothelial cells. Experiments in vitro showed that the frequency of carotid nerve discharges recorded from CBs perfused and superfused under normoxic conditions was not significantly modified by TNF-alpha, but that the enhanced frequency of chemosensory discharges recorded along responses to hypoxic stimulation was transiently diminished in a dose-dependent manner by TNF-alpha injections. The results suggest that the CB may operate as a sensor for immune signals, that the CB exhibits histological features of acute inflammation induced by LPS, that TNF-alpha may participate in LPS-induced changes in chemosensory activity and that some pathophysiological reactions to high levels of LPS in the bloodstream may originate from changes in CB function.
  • Thumbnail Image
    Item
    Replenishment of type VII collagen and re-epithelialization of chronically ulcerated skin after intradermal administration of allogeneic mesenchymal stromal cells in two patients with recessive dystrophic epidermolysis bullosa
    (INFORMA HEALTHCARE, 2010) Conget, Paulette; Rodriguez, Fernando; Kramer, Susanne; Allers, Carolina; Simon, Valeska; Palisson, Francis; Gonzalez, Sergio; Yubero, Maria J.
    In animal models it has been shown that mesenchymal stromal cells (MSC) contribute to skin regeneration and accelerate wound healing. We evaluated whether allogeneic MSC administration resulted in an improvement in the skin of two patients with recessive dystrophic epidermolysis bullosa (RDEB; OMIM 226600). Patients had absent type VII collagen immunohistofluorescence and since birth had suffered severe blistering and wounds that heal with scarring. Vehicle or 0.5x10
  • No Thumbnail Available
    Item
    Understanding current therapies in metastatic melanoma
    (SOC MEDICA SANTIAGO, 2016) Rodriguez, Rocio; Para, Angela; Gonzalez, Sergio; Molgo, Montserrat; Droppelmann, Nicolas; Acevedo, Francisco; Pena, Jose; Uribe, Pablo
    Cutaneous melanoma is a highly aggressive tumor developing from melanocytes, its incidence is increasing, and prognosis in advanced stages is daunting. New therapies have been approved during the recent years with unprecedented results, including inhibitors of MAPK/ERK pathway and immune checkpoint blockade (anti-cytotoxic T lymphocyte antigen- 4 (CTLA-4) as ipilimumab, anti-programmed cell death protein 1 (PD-L1) as pembrolizumab and anti-programmed cell death protein 1 ligand (PD-L1), among many others). The aim of this paper is to review currently available metastatic melanoma therapies focusing mainly on new therapies that have demonstrated effectiveness, after several decades of little progress in the treatment of this disease.