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Browsing by Author "Corvalan, Alejandro"

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Analytical detection of immunoglobulin heavy chain gene rearrangements in gastric lymphoid infiltrates by peak area analysis of the melting curve in the LightCycler System
(ELSEVIER SCIENCE INC, 2007) Retamales, Eduardo; Rodriguez, Luis; Guzman, Leda; Aguayo, Francisco; Palma, Mariana; Backhouse, Claudia; Argandona, Jorge; Riquelme, Erick; Corvalan, Alejandro
Because it is difficult to differentiate gastric mucosa-associated lymphoid tissue (MALT) lymphoma from chronic gastritis in gastric lymphoid infiltrates, molecular detection of monoclonality through immunoglobulin heavy chain (IgH) gene rearrangements is commonly performed. However, heterogeneity in the performance and results obtained from IgH gene rearrangements has been reported. To improve the accuracy in the diagnosis of gastric lymphoid infiltrates, we developed an analytical approach based on one-peak area analysis of the melting curve in the LightCycler System. Using a training-testing approach, the likelihood ratio method was selected to find a discriminative function of 4.64 in the training set (10 gastric MALT lymphomas and 10 chronic gastritis cases). This discriminative function was validated in the testing set (five gastric MALT lymphomas, six abnormal lymphocytic infiltrates with subsequently demonstrated gastric MALT lymphomas, and six cases of chronic gastritis). All but one case of gastric MALT lymphoma, as well as abnormal lymphocytic infiltrates, clustered under 4.64, and all chronic gastritis cases clustered above 4.64. These results were validated by conventional electrophoreses confirming one or two sharp bands in cases of gastric MALT lymphomas and a smear of multiple bands in cases of chronic gastritis. Analytical detection of IgH gene rearrangement in gastric lymphoid infiltrates by one-peak area analysis correctly distinguishes gastric MALT lymphomas from chronic gastritis, even in cases with diagnosis of abnormal lymphocytic infiltrates.
DNA methylation profile in diffuse type gastric cancer: evidence for hypermethylation of the BRCA 1 promoter region in early-onset gastric carcinogenesis
(SOC BIOLGIA CHILE, 2008) Bernal, Carolina; Vargas, Macarena; Ossandon, Francisco; Santibanez, Eudocia; Urrutia, Julio; Luengo, Victor; Zavala, Luis F.; Backhouse, Claudia; Palma, Mariana; Argandona, Jorge; Aguayo, Francisco; Corvalan, Alejandro
Diffuse type gastric carcinoma is the most aggressive type of gastric cancer. This type Of tumor is not preceded by precancerous changes and is associated with carly-onset and hereditary syndromes. To test the hypothesis that DNA methylation profile Would be useful for molecular classification of the diffuse type gastric carcinoma, DNA methylation patterns of the CpG Island of 17 genes were studied in 104 cases and 47 normal adjacent gastric mucosa by Methylation-specific PCR, Immunohistochemistry and Hierarchical Clustering analysis. The most frequent methylated genes were FHIT, E-cadherin, BRCA1 and APC (>50%), followed by p14, p16, p15, p73, MGMT and SEMA3B (20-49%). Hierarchical clustering analysis reveals four groups with different clinical features. The first was characterized by hypermethylation of BRCA 1 and younger age (<45 years old), and the second by hypermethylation of p14 and p 16 genes, male. predominance and Epstein-Barr virus infection. The third group was characterized by hypermethylation of FHIT and antrum located tumors and the fourth was not associated with any clinical variables. In normal adjacent mucosa only the p73 gene was significantly less methylated in comparison to tumor mucosa. DNA methylation identified subgroups of diffuse type gastric cancer. Hypermethylation of BRCA I associated with Young age suggests a role in early-onset gastric carcinoma.
E-cadherin and beta-catenin expression in Epstein-Barr virus-associated gastric carcinoma and their prognostic significance
(W J G PRESS, 2007) Koriyama, Chihaya; Akiba, Suminori; Itoh, Tetsuhiko; Sueyoshi, Kazunobu; Minakami, Yoshie; Corvalan, Alejandro; Yonezawa, Suguru; Eizuru, Yoshito
AIM: To examine the role of E-cadherin and betacatenin in carcinogenesis and to assess their prognostic implication in Epstein-Barr virus-associated gastric carcinomas (EBV-GCs).
Epstein-Barr virus-associated primary lymphoepitheliomalike carcinoma of the esophagus
(LIPPINCOTT WILLIAMS & WILKINS, 2007) Valbuena, Jose Rafael; Retamal, Yasmina; Bernal, Carolina; Eizuru, Yoshito; Corvalan, Alejandro
Primary lymphoepitheliomalike carcinomas (LELC) of the esophagus are uncommon, with only 29 previously reported cases in the literature. Primary LELC of the esophagus is associated with Epstein-Barr virus (EBV). We herein report a 52-year-old man who presented with dysphagia and weight loss and was found to have a polypoid mass in the middle esophagus. Pathologic examination showed LELC. EBV infection was demonstrated by immunohistochemical detection of EBNA-1 in neoplastic cells and polymerase chain reaction amplification for EBNA-3C, BamHI-F, and W1/I1 regions but not by in situ hybridization by EBER-1 transcripts. EBV genotyping analysis demonstrated infection by a novel type "i"/XhoI loss recombinant strain. Although it is accepted that polymorphisms at BamHI-W1/I1 region cosegregate with polymorphisms at XhoI restriction site, this novel recombinant EBV has been identified in healthy donors and in nasal NK/T-cell lymphoma. To our knowledge, this is the first report that describes this recombinant type "i"/XhoI loss EBV strain in a primary LELC of the esophagus.
Frequent epigenetic inactivation of chromosome 3p candidate tumor suppressor genes in gallbladder carcinoma
(ELSEVIER IRELAND LTD, 2007) Riquelme, Erick; Tang, Moying; Baez, Sergio; Diaz, Alfonso; Pruyas, Martha; Wistuba, Ignacio I.; Corvalan, Alejandro
Gallbladder carcinoma (GBC) is a highly malignant neoplasm that represents the leading cause of death for cancer in Chilean females. There is limited information about the molecular abnormalities involved in its pathogenesis. We have identified a number of molecular changes in GBC, including frequent allelic losses at chromosome 3p regions. Four distinct 3p sites (3p12, 3p14.2, 3p21.3 and 3p22-24) with frequent and early allelic losses in the sequential pathogenesis of this neoplasm have been detected. We investigated epigenetic and genetic abnormalities in GBC affecting 6 candidate tumor suppressor genes (TSG) located in chromosome 3p, including DUTT1 (3p12), FHIT(3p14.2), BLU, RASSF1A, SEMA3B and hMLH1 (3p21.3). DNA extracted from frozen tissue obtained from 50 surgical resected GBCs was examined for gene promoter methylation using MSP (methylation-specific PCR) technique after bisulfite treatment in all 6 genes. In addition, we performed PCR-based mutation examination using SSCP in FHIT and RASSF1A genes and loss of heterozygosity (LOH) analysis using microdissected tissue in a subset of tumors for the 3p21.3 region with 8 microsatellite markers. A very high frequency of GBC methylation was detected in SEMA3B (46/50, 92%) and FHIT (33/50, 66%), inter-mediate incidences in BLU (13/50, 26%) and DUTT1 (11/50, 22%) and very low frequencies in RASSF1A (4/50, 8%) and hMLH1 (2/50, 4%). Allelic loss at 3p21.3 was found in nearly half of the GBCs examined. We conclude that epigenetic inactivation by abnormal promoter methylation is a frequent event in chromosome 3p candidate TSGs in GBC pathogenesis, especially affecting genes SEMA3B (3p21.3) and FHIT (3p 14.2). (c) 2006 Elsevier Ireland Ltd. All rights reserved.
Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile
(W J G PRESS, 2006) Castillo, Andres; Aguayo, Francisco; Koriyama, Chihaya; Torres, Miyerlandi; Carrascal, Edwin; Corvalan, Alejandro; Roblero, Juan P.; Naquira, Cecilia; Palma, Mariana; Backhouse, Claudia; Argandona, Jorge; Itoh, Tetsuhiko; Shuyama, Karem; Eizuru, Yoshito; Akiba, Suminori
AIM: To examine the presence of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively.
In vitro evaluation and molecular docking of QS-21 and quillaic acid from Quillaja saponaria Molina as gastric cancer agents
(NATURE RESEARCH, 2020) Guzman, Leda; Villalon, Katherine; Jose Marchant, Maria; Elena Tarnok, Maria; Cardenas, Pilar; Aquea, Gisela; Acevedo, Waldo; Padilla, Leandro; Bernal, Giuliano; Molinari, Aurora; Corvalan, Alejandro
The cytotoxic mechanism of the saponin QS-21 and its aglycone quillaic acid (QA) was studied on human gastric cancer cells (SNU1 and KATO III). Both compounds showed in vitro cytotoxic activity with IC50 values: 7.1 mu M (QS-21) and 13.6 mu M (QA) on SNU1 cells; 7.4 mu M (QS-21) and 67 mu M (QA) on KATO III cells. QS-21 and QA induce apoptosis on SNU1 and KATO III, as demonstrated by TUNEL, Annexin-V and Caspase Assays. Additionally, we performed in silico docking studies simulating the binding of both triterpenic compounds to key proteins involved in apoptotic pathways. The binding energies (G(bin)) thus calculated, suggest that the pro-apoptotic protein Bid might be a plausible target involved in the apoptotic effect of both triterpenic compounds. Although QA shows some antiproliferative effects on SNU1 cells cultured in vitro, our results suggest that QS-21 is a more powerful antitumor agent, which merits further investigation regarding their properties as potential therapeutic agents for gastric cancer.
Lynch syndrome: selection of families by microsatellite instability and immunohistochemistry
(SOC MEDICA SANTIAGO, 2012) Maria Wielandt, Ana; Zarate, Alejandro J.; Hurtado, Claudia; Orellana, Paulina; Alvarez, Karin; Pinto, Eliana; Contreras, Luis; Corvalan, Alejandro; Kronberg, Udo; Lopez Koestner, Francisco
Background: Selection of patients with Lynch Syndrome (LS) for a genetic study involves the application of clinical criteria. To increase the rate of identification of mutations, the use of molecular studies as Microsatellite Instability (MSI) and Immunohistochemistry (IHC) in the tumor has been proposed. Aim: To demonstrate the usefulness of MSI and IHC in the detection of mutations in patients with LS. Material and Methods: From our Familial Colorectal Cancer Registry, families suspected of LS were selected according to Amsterdam or Bethesda clinical criteria. Screening of germline mutations of MLH1, MSH2 and MSH6 genes was performed. In addition, analysis of MS I and IHC were performed in colorectal tumors. Results: A total of 35 families were studied (19 met Amsterdam and 16 met Bethesda criteria). Twenty one families harbored a germline alteration in MLH1, MSH2 or MSH6 (18 Amsterdam and 3 Bethesda). In these families, eighteen different alterations were found, 15 of which were mutations and 3 corresponded to variants of uncertain pathogenicity. On the other hand, 80% of the tumors showed positive microsatellite instability (27 MSI-high and 1 MSI-low), and immunohistochemical testing showed that 77% of tumors had the loss of a protein. Correlation between results of tumor molecular studies and the finding of germline nucleotide change showed that IHC and MSI predicted mutations in 81 and 100% of patients, respectively. Conclusions: MSI and IHC can efficiently select patients with a high probability of carrying a mutation in DNA repair genes. (Rev Med Chile 2012; 140: 1132-1139).
Mismatch repair expression in testicular cancer predicts recurrence and survival
(WILEY-LISS, 2008) Velasco, Alfredo; Corvalan, Alejandro; Wistuba, Ignacio I.; Riquelme, Erick; Chuaqui, Rodrigo; Majerson, Alejandro; Leach, Fredrick S.
We investigated mismatch repair (MMR) gene expression in testicular cancer as a molecular marker for clinical outcome (recurrence, response to chemotherapy and death) using protein expression and specific genetic alterations associated with the presence or absence of MMR activity. One hundred sixty-two cases of paraffin-embedded testis cancer specimens were subjected to immunohistochemical analysis using monoclonal antibody for MLH1 and MSH2 MMR proteins and genetic analysis using specific polymorphic markers. The degree of MMR immunoreactivity and genetic instability in the form of loss of heterozygosity (LOH) and/or microsatellite instability (MSI) were determined by comparing matched normal and tumor tissue. The degree of immunohistochemical staining for MMR expression was associated with a shorter time to tumor recurrence, resistance to chemotherapy and death. Furthermore, clinical relapse and cancer specific death was also associated with tumors exhibiting a high degree of MSI, p = 0.01 and 0.04, respectively. In contrast, LOH was not associated with recurrence, resistance to chemotherapy or death. Therefore, MMR expression defines testis cancers with distinct molecular properties and clinical behavior, such that tumors with decreased MMR immunostaining and/or increased frequency of MSI have a shorter time to recurrence and death despite chemotherapy. (c) 2007 Wiley-Liss, Inc.
Promoter hypermethylation of BRCA1 correlates with absence of expression in hereditary breast cancer tumors
(TAYLOR & FRANCIS INC, 2008) Tapia, Teresa; Smalley, Susan V.; Kohen, Paulina; Munoz, Alex; Solis, Luisa M.; Corvalan, Alejandro; Faundez, Paola; Devoto, Luigi; Camus, Mauricio; Alvarez, Manuel; Carvallo, Pilar
Germline mutations in BRCA1 account for a low proportion of hereditary cases in diverse populations. Several efforts have been made to find new genes involved in the inheritance of breast cancer with no success until today. The participation of BRCA1 in the development of breast cancer has been proposed in several studies where hypermethylation of its promoter and a decrease in expression has been reported for sporadic cases and one study on familial cases. To explore the participation of BRCA1 in hereditary carcinogenesis through a different mechanism than the inheritance of germline mutations, we studied the methylation status of its promoter in breast tumors, from patients previously screened for BRCA1/BRCA2 germline mutations. We also determined the presence of the BRCA1 protein in these tumors and correlated both events with tumor grade, hormone receptors and ERBB2 presence. Promoter hypermethylation of the BRCA1 gene was detected in 51% of our biopsies, among which 67% did not express the respective protein. This result leads us to suggest that hypermethylation could be considered as an inactivating mechanism for BRCA1 expression, either as a first or second hit. Moreover, a number of biopsies with absence of expression on BRCA1 showed negative detection of estrogen and progesterone receptors, a similar phenotype to BRCA1 mutated breast tumors.
Serial analysis of gene expression identifies connective tissue growth factor expression as a prognostic biomarker in gallbladder cancer
(AMER ASSOC CANCER RESEARCH, 2008) Alvarez, Hector; Corvalan, Alejandro; Roa, Juan C.; Argani, Pedram; Murillo, Francisco; Edwards, Jennifer; Beaty, Robert; Feldmann, Georg; Hong, Seung Mo; Mullendore, Michael; Roa, Ivan; Ibanez, Luis; Pimente, Fernando; Diaz, Alfonso; Riggins, Gregory J.; Maitra, Anirban
Background: Gallbladder cancer (GBC) is an uncommon neoplasm in the United States, but one with high mortality rates. This malignancy remains largely understudied at the molecular level such that few targeted therapies or predictive biomarkers exist.

Browsing by Author "Corvalan, Alejandro"

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