Browsing by Author "Kronberg, Udo"

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    Detection of lymphatic micrometastases in patients with stages I and II colorectal cancer: Impact on five-year survival
    (2004) Kronberg, Udo; López Köstner, Francisco; Soto, Gonzalo; Zuñiga A., Alvaro; Wistuba Oyarzún, Ignacio; Miranda, Vanessa; Pinto, Eliana; Viviani García, Paola; Marshall Rivera, Guillermo
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    EGFR pathway subgroups in Chilean colorectal cancer patients, detected by mutational and expression profiles, associated to different clinicopathological features
    (2017) Alvarez, Karin; Orellana, Paulina; Villarroel, Cynthia; Contreras, Luis; Kawachi, Hiroshi; Kobayashi, Maki; Wielandt, Ana María; De la Fuente, Marjorie; Triviño, Juan Carlos; Carvallo de Saint Quentin, Pilar; Kronberg, Udo; López-Köstner, Francisco
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    Interleukin 33/ST2 Axis Components Are Associated to Desmoplasia, a Metastasis-Related Factor in Colorectal Cancer
    (2019) Landskron, Glauben; De la Fuente Lopez, Marjorie; Dubois-Camacho, Karen; Diaz-Jimenez, David; Orellana-Serradell, Octavio; Romero, Diego; Sepulveda, Santiago A.; Salazar, Christian; Parada-Venegas, Daniela; Quera, Rodrigo; Simian, Daniela; Gonzalez, Maria-Julieta; Kronberg, Udo; Abedrapo, Mario; Gallegos, Ivan; Contreras, Hector R.; Pena, Cristina; Diaz-Araya, Guillermo; Carlos Roa, Juan; Hermoso, Marcela A.
    In colorectal cancer (CRC), cancer-associated fibroblasts (CAFs) are the most abundant component from the tumor microenvironment (TM). CAFs facilitate tumor progression by inducing angiogenesis, immune suppression and invasion, thus altering the organization/composition of the extracellular matrix (i.e., desmoplasia) and/or activating epithelial-mesenchymal transition (EMT). Soluble factors from the TM can also contribute to cell invasion through secretion of cytokines and recently, IL-33/ST2 pathway has gained huge interest as a protumor alarmin, promoting progression to metastasis by inducing changes in TM. Hence, we analyzed IL-33 and ST2 content in tumor and healthy tissue lysates and plasma from CRC patients. Tissue localization and distribution of these molecules was evaluated by immunohistochemistry (using localization reference markers a-smooth muscle actin or alpha-SMA and E-cadherin), and clinical/histopathological information was obtained from CRC patients. In vitro experiments were conducted in primary cultures of CAFs and normal fibroblasts (NFs) isolated from tumor and healthy tissue taken from CRC patients. Additionally, migration and proliferation analysis were performed in HT29 and HCT116 cell lines. It was found that IL-33 content increases in left-sided CRC patients with lymphatic metastasis, with localization in tumor epithelia associated with abundant desmoplasia. Although ST2 content showed similarities between tumor and healthy tissue, a decreased immunoreactivity was observed in left-sided tumor stroma, associated to metastasis related factors (advanced stages, abundant desmoplasia, and presence of tumor budding). A principal component analysis (including stromal and epithelial IL-33/ST2 and alpha-SMA immunoreactivity with extent of desmoplasia) allowed us to distinguish clusters of low, intermediate and abundant desmoplasia, with potential to develop a diagnostic signature with benefits for further therapeutic targets. IL-33 transcript levels from CAFs directly correlated with CRC cell line migration induced by CAFs conditioned media, with rhlL-33 inducing a mesenchymal phenotype in HT29 cells. These results indicate a role of IL-33/ST2 in tumor microenvironment, specifically in the interaction between CAFs and epithelial tumor cells, thus contributing to invasion and metastasis in left-sided CRC, most likely by activating desmoplasia.
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    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).
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    Rectal diffuse large B cell lymphoma appearing after immunosuppression for ulcerative colitis. Report of one case
    (SOC MEDICA SANTIAGO, 2017) Quera, Rodrigo; Flores, Lilian; Simian, Daniela; Kronberg, Udo; Teresa Vial, Maria; Ladron De Guevara, David; Jose Garcia Rodriguez, Maria
    Primary colorectal lymphoma is a rare form of presentation of gastrointestinal tract lymphomas. Inflammatory bowel disease and its treatment are risk factors for its development. We report a 47-year-old male patient with Ulcerative Colitis of two years of evolution, treated initially with azathioprine and later on with infliximab. Due to a relapse in symptoms after the second dose of infliximab, a new coloncoscopy was performed showing a rectal ulcerative lesion, corresponding to a large cell Non-Hodgkin's Lymphoma. The patient was successfully treated with RCHOP chemotherapy (Rituximab cyclophosphamide doxorubicin vincristine prednisone). He is currently in disease remission.
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    Resultados y eventos adversos de la sigmoidectomía por cáncer: laparoscopia versus laparotomía
    (2008) Zárate, Alejandro José; López Köstner, Francisco; Loureiro Pérez, Carolina Andrea; Pinedo Mancilla, George; Molina Martin, María Paz; Kronberg, Udo; Viviani García, Paola
    Objetivo: Comparar resultados y complicaciones inmediatas al realizar una sigmoidectomía laparoscópica (SL) versus abierta (SA) en pacientes con cáncer de colon sigmoides. Material y método: Inclusión prospectiva y consecutiva, mediante protocolo de estudio de pacientes operados mediante SL entre el 2000 y el 2006. Análisis comparativo caso-control, mediante pareo según edad, sexo y ASA entre pacientes operados mediante SL con SA. Análisis por intención de tratamiento, mediante test t de Student, chi cuadrado, Mann-Withney y exacto de Fischer; consideramos estadísticamente significativo p <0,05. Resultados: Treinta y dos pacientes por grupo fueron comparados. Los grupos (SL v/s SA) fueron similares estadísticamente en edad (65,6 v/s 67,3 años), sexo (femenino 31,25%), y ASA (p> 0,05). La mediana del tiempo operatorio fue mayor en SL (220 v/s 172 minutos, p <0,01). Un 9,3% se convirtió a técnica abierta en SL. El tiempo medio a la expulsión de gases y realimentación con líquidos fue menor en SL (2 v/s 4 días, p<0,01 y 3 v/s 5 días, p< 0,01). La estadía media postquirúrgica (5 v/s 8 días p<0,01) fue menor en SL. Las complicaciones postoperatorias médicas, fueron menores en SL (9,3% v/s 37,5% p<0,01), pero las quirúrgicas fueron iguales (6,25% cada grupo). Los linfonodos resecados y tamaños de piezas operatorias fueron similares (SL v/s SA: 22,7 v/s 22,1 linfonodos p= 0,9 y 21,8 v/s 19,3 cm. p= 0,2). Conclusión: El desarrollo de la cirugía laparoscópica colorrectal mediante un protocolo, permite realizar la SL por cáncer con resultados quirúrgicos similares a la SA.