Actinic cheilitis (AC) is a pre-malignant lesion caused by ultraviolet (UV) radiation and charact... more Actinic cheilitis (AC) is a pre-malignant lesion caused by ultraviolet (UV) radiation and characterized by epithelial and connective tissue alterations. Mast cells (MCs), key contributors to solar elastosis in murine UV-irradiated skin, were characterized in order to assess their potential contribution to connective tissue degeneration in AC. Actinic cheilitis (n = 15) and normal lip (n = 8) biopsies were stained immunohistochemically for tryptase and enzymehistochemically for chymase to determine MC density and protease content. MC subpopulations (i.e. MC(T) containing only tryptase, and MC(TC) containing chymase and tryptase) and their distribution were also determined. Mast cells and their proteases were increased in AC as compared with normal lip (P < 0.0001), and appeared degranulated especially around elastotic areas. MC(T) predominated over MC(TC) in AC and normal lip (P < 0.05). However, in AC MC(T) were increased in the epithelium/connective junction and connective area (P < 0.05), while in normal lip MC(T) predominated in connective and submucosal areas (P < 0.05). The results suggest that increased MC density and protease content may contribute to elastosis formation in AC. In addition, changes in MC(T) distribution may favor AC malignization.
Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on pr... more Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population‐based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non‐genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision‐recall curve (AUC‐PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC‐PR...
Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer... more Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence “gallstones → dysplasia → GBC”. In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 a...
We report the case of a patient who presented a pineal tumor. A partial resection was performed. ... more We report the case of a patient who presented a pineal tumor. A partial resection was performed. The biopsy showed a glioneuroma rosette forming tumor, considered as WHO grade I. The patient was observed for 13 months and experienced significant tumor growth. Radiotherapy was performed. Instead of scarce evidence of the topic and treatment modalities in this type of tumors; radiotherapy was performed. The patient has been stable and asymptomatic.
Otorhinolaryngology Clinics - An International Journal, 2014
We report on a patient who presented with pain and swelling to the left maxillary region of the f... more We report on a patient who presented with pain and swelling to the left maxillary region of the face. A biopsy of the area was performed and subsequently diagnosed as maxillary carcinosarcoma (CCS). After reviewing the pathology results and the size of the tumor, it was decided that a radical dissection, followed by radiation therapy was the best option. How to cite this article Sepúlveda I, Frelinghuysen M, García C, Spencer ML, Platín E, Alarcon J, Ulloa D. Maxillary Carcinosarcoma: A Case Report and Review of the Literature. Int J Otorhinolaryngol Clin 2014;6(3):114117.
We report the case of a patient who presented to the ENT service with left facial swelling of 5 m... more We report the case of a patient who presented to the ENT service with left facial swelling of 5 months duration. Imaging studies revealed a dense expansive mass confined to the inside of the left deep parotid lobule and moderate enhancement following contrast media injection. Subsequently, a biopsy confirmed the presence of an oncocytoma. The patient was treated with total parotidectomy, complete tumor resection and sparing facial nerve surgery. Today, the patient is disease free and has no complications.
The genomic characterization of solid tumors and a rapidly growing repertoire of target drugs are... more The genomic characterization of solid tumors and a rapidly growing repertoire of target drugs are revolutionizing cancer treatment. Next-generation sequencing (NGS) panels are progressively used in clinical practice for target therapy in high-income countries. In contrast, limited access to tumor sequencing, among other barriers, precludes precision cancer treatment in low- and middle-income countries. To build towards the implementation of precision oncology in Chile and Latin America, we designed a 25-gene panel that contains predictive biomarkers for currently or near-future available therapies in Latin America. Library preparation was optimized to account for DNA integrity variability in Formalin-Fixed Paraffin-Embedded (FFPE) tissue. The bioinformatic pipeline removes FFPE-induced artifacts and known germline variants; while identifying possible discrepancies in somatic mutations due to Latin Americans’ underrepresentation in the reference genome databases. Analytic sensitivity...
Introduction Therapies that target activating Egfr, Alk, Ros1 and other mutations have become fir... more Introduction Therapies that target activating Egfr, Alk, Ros1 and other mutations have become first-line treatments that improve NSCLC patient life expectancy. Latin-American patients are poorly represented in clinical trials and in genomic databases, thus little is known about the prevalence of actionable mutations in this population. This study characterizes, for the first time, the somatic mutations found in 52 actionable genes, and describe a novel set of potentially actionable mutations, in NSCLC patients from Chile, Brazil and Peru, while correlating these genomic occurrences with relevant clinical, demographic and pathology aspects. Methods 1732 subjects diagnosed with NSCLC were analyzed. DNA and RNA were sequenced using a 52 genes NGS panel. Mutations were annotated using the Variant Effect Predictor, COSMIC, OncoKB and the Cancer Genome Interpreter to categorize somatic mutations. Results We found a total of 1713 mutations with 626 (36.5%) novel, potentially driver mutatio...
Next-generation sequencing (NGS) is progressively being used in clinical practice. However, sever... more Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America. Library preparation was optimized to account for low DNA integrity observed in formalin-fixed paraffin-embedded tissue. The workflow includes an automated bioinformatic pipeline that accounts for the underrepresentation of Latin Americans in genome databases. The panel detected small insertions, deletions, and single nucleotide variants down to allelic frequencies of 0.05 with high sensitivity, specificity, and reproducibility. The workflow was validated in 272 clinical samples from several solid tumor types, including gallbladder (GBC). More than 50 biomarkers were detected in these samples, mainly in BRCA...
Actinic cheilitis (AC) is a pre-malignant lesion caused by ultraviolet (UV) radiation and charact... more Actinic cheilitis (AC) is a pre-malignant lesion caused by ultraviolet (UV) radiation and characterized by epithelial and connective tissue alterations. Mast cells (MCs), key contributors to solar elastosis in murine UV-irradiated skin, were characterized in order to assess their potential contribution to connective tissue degeneration in AC. Actinic cheilitis (n = 15) and normal lip (n = 8) biopsies were stained immunohistochemically for tryptase and enzymehistochemically for chymase to determine MC density and protease content. MC subpopulations (i.e. MC(T) containing only tryptase, and MC(TC) containing chymase and tryptase) and their distribution were also determined. Mast cells and their proteases were increased in AC as compared with normal lip (P < 0.0001), and appeared degranulated especially around elastotic areas. MC(T) predominated over MC(TC) in AC and normal lip (P < 0.05). However, in AC MC(T) were increased in the epithelium/connective junction and connective area (P < 0.05), while in normal lip MC(T) predominated in connective and submucosal areas (P < 0.05). The results suggest that increased MC density and protease content may contribute to elastosis formation in AC. In addition, changes in MC(T) distribution may favor AC malignization.
Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on pr... more Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population‐based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non‐genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision‐recall curve (AUC‐PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC‐PR...
Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer... more Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence “gallstones → dysplasia → GBC”. In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 a...
We report the case of a patient who presented a pineal tumor. A partial resection was performed. ... more We report the case of a patient who presented a pineal tumor. A partial resection was performed. The biopsy showed a glioneuroma rosette forming tumor, considered as WHO grade I. The patient was observed for 13 months and experienced significant tumor growth. Radiotherapy was performed. Instead of scarce evidence of the topic and treatment modalities in this type of tumors; radiotherapy was performed. The patient has been stable and asymptomatic.
Otorhinolaryngology Clinics - An International Journal, 2014
We report on a patient who presented with pain and swelling to the left maxillary region of the f... more We report on a patient who presented with pain and swelling to the left maxillary region of the face. A biopsy of the area was performed and subsequently diagnosed as maxillary carcinosarcoma (CCS). After reviewing the pathology results and the size of the tumor, it was decided that a radical dissection, followed by radiation therapy was the best option. How to cite this article Sepúlveda I, Frelinghuysen M, García C, Spencer ML, Platín E, Alarcon J, Ulloa D. Maxillary Carcinosarcoma: A Case Report and Review of the Literature. Int J Otorhinolaryngol Clin 2014;6(3):114117.
We report the case of a patient who presented to the ENT service with left facial swelling of 5 m... more We report the case of a patient who presented to the ENT service with left facial swelling of 5 months duration. Imaging studies revealed a dense expansive mass confined to the inside of the left deep parotid lobule and moderate enhancement following contrast media injection. Subsequently, a biopsy confirmed the presence of an oncocytoma. The patient was treated with total parotidectomy, complete tumor resection and sparing facial nerve surgery. Today, the patient is disease free and has no complications.
The genomic characterization of solid tumors and a rapidly growing repertoire of target drugs are... more The genomic characterization of solid tumors and a rapidly growing repertoire of target drugs are revolutionizing cancer treatment. Next-generation sequencing (NGS) panels are progressively used in clinical practice for target therapy in high-income countries. In contrast, limited access to tumor sequencing, among other barriers, precludes precision cancer treatment in low- and middle-income countries. To build towards the implementation of precision oncology in Chile and Latin America, we designed a 25-gene panel that contains predictive biomarkers for currently or near-future available therapies in Latin America. Library preparation was optimized to account for DNA integrity variability in Formalin-Fixed Paraffin-Embedded (FFPE) tissue. The bioinformatic pipeline removes FFPE-induced artifacts and known germline variants; while identifying possible discrepancies in somatic mutations due to Latin Americans’ underrepresentation in the reference genome databases. Analytic sensitivity...
Introduction Therapies that target activating Egfr, Alk, Ros1 and other mutations have become fir... more Introduction Therapies that target activating Egfr, Alk, Ros1 and other mutations have become first-line treatments that improve NSCLC patient life expectancy. Latin-American patients are poorly represented in clinical trials and in genomic databases, thus little is known about the prevalence of actionable mutations in this population. This study characterizes, for the first time, the somatic mutations found in 52 actionable genes, and describe a novel set of potentially actionable mutations, in NSCLC patients from Chile, Brazil and Peru, while correlating these genomic occurrences with relevant clinical, demographic and pathology aspects. Methods 1732 subjects diagnosed with NSCLC were analyzed. DNA and RNA were sequenced using a 52 genes NGS panel. Mutations were annotated using the Variant Effect Predictor, COSMIC, OncoKB and the Cancer Genome Interpreter to categorize somatic mutations. Results We found a total of 1713 mutations with 626 (36.5%) novel, potentially driver mutatio...
Next-generation sequencing (NGS) is progressively being used in clinical practice. However, sever... more Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America. Library preparation was optimized to account for low DNA integrity observed in formalin-fixed paraffin-embedded tissue. The workflow includes an automated bioinformatic pipeline that accounts for the underrepresentation of Latin Americans in genome databases. The panel detected small insertions, deletions, and single nucleotide variants down to allelic frequencies of 0.05 with high sensitivity, specificity, and reproducibility. The workflow was validated in 272 clinical samples from several solid tumor types, including gallbladder (GBC). More than 50 biomarkers were detected in these samples, mainly in BRCA...
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Papers by Loreto Spencer