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Polymorphisms within autophagy-related genes as susceptibility biomarkers for m...

Clavero, Esther; Sanchez-Maldonado, José Manuel; Macauda, Angelica; Ter Horst, Rob; Marques, Maria Belém Sousa Sampaio; Jurczyszyn, Artur

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promot...


The usefulness of an Online Simplified Screening Questionnaire (SSQ) in identif...

Vazquez, Fabiana L.; Silveira, Henrique C. S.; Otero, Ubirani B.; Hosokawa, Thais T.; Fregnani, José Humberto T. G.; Longatto, Adhemar; Reis, R. M.

To obtain a history of occupational exposure in the workplace, the questionnaire is one of the main sources of information. The aim of this study was to develop an online questionnaire using the REDCap data management platform based on the Work-Related Cancer Surveillance Guidelines, reported by the Brazilian National Cancer Institute. Several issues were taken into consideration for its routine application. It...


The Barretos Cancer Hospital Animal Facility: implementation and results of a d...

Teixeira, Silvia A.; Luzzi, Mayara de Cassia; Martin, Ana Carolina Baptista Moreno; Duarte, Terence Teixeira; Leal, Mônica de Oliveira

The Barretos Cancer Hospital Animal Facility (BCHAF) is a unique facility in Brazil exclusively dedicated to working with animal models for cancer research. In this article, we briefly present our modern facility and the main experiments performed, focusing on mutant strains of mice (PTCH-knockout and <i>Apc<sup>Min</sup></i> mice), xenograft models, and patient-derived xenografts (PDXs). Our results show the p...


Comprehensive molecular landscape of cetuximab resistance in head and neck canc...

Gomes, Izabela N. F.; Silva-Oliveira, Renato J. da; Silva, Luciane Sussuchi da; Martinho, Olga; Evangelista, Adriane F.; Helvoort Lengert, André van

Cetuximab is the sole anti-EGFR monoclonal antibody that is FDA approved to treat head and neck squamous cell carcinoma (HNSCC). However, no predictive biomarkers of cetuximab response are known for HNSCC. Herein, we address the molecular mechanisms underlying cetuximab resistance in an in vitro model. We established a cetuximab resistant model (FaDu), using increased cetuximab concentrations for more than eigh...


WNK2 inhibits autophagic flux in human glioblastoma cell line

Alves, Ana Laura Vieira; Costa, Angela Margarida; Martinho, Olga; da Silva, Vinicius Duval; Jordan, Peter; Silva, Viviane Aline Oliveira; Reis, R. M.

Autophagy is a cell-survival pathway with dual role in tumorigenesis, promoting either tumor survival or tumor death. <i>WNK2</i> gene, a member of the WNK (with no lysine (K)) subfamily, acts as a tumor suppressor gene in gliomas, regulating cell migration and invasion; however, its role in autophagy process is poorly explored. The <i>WNK2</i>-methylated human glioblastoma cell line A172 WT (wild type) was com...


Establishment, molecular and biological characterization of HCB-514: a novel hu...

Rosa, Marcela Nunes; Evangelista, Adriane Feijó; Leal, Letícia Ferro; De Oliveira, Cristina Mendes; Silva, Viviane Aline Oliveira

Cervical cancer is the fourth most common cancer in women. Although cure rates are high for early stage disease, clinical outcomes for advanced, metastatic, or recurrent disease remain poor. To change this panorama, a deeper understanding of cervical cancer biology and novel study models are needed. Immortalized human cancer cell lines such as HeLa constitute crucial scientific tools, but there are few other ce...


Comparison of protocols for removal of melanin from genomic DNA to optimize PCR...

Vicente, Anna Luiza Silva Almeida; Bianchini, Raquel Alves; Laus, Ana Carolina; Macedo, Graziela; Reis, R. M.; Vazquez, Vinicius de Lima

Melanin is produced by melanocytes and protects against DNA damage by ultraviolet light. Unfortunately, the melanin protein present in melanoma tumor cells is often co-purified during DNA extraction, and this contamination may inhibit subsequent PCR methods, which directly impacts research applications and the molecular diagnostic tests needed for targeted therapeutics. There are presently no described purifica...


Mutation profling of cancer drivers in Brazilian colorectal cancer

Santos, Wellington dos; Sobanski, Thais; Carvalho, Ana Carolina de; Evangelista, Adriane Feijó; Matsushita, Marcus; Berardinelli, Gustavo Nóriz

The molecular basis of colorectal cancer (CRC) can guide patient prognosis and therapy. In Brazil, knowledge on the CRC mutation landscape is limited. Here, we investigated the mutation profile of 150 cancer-related genes by next-generation sequencing and associated with microsatellite instability (MSI) and genetic ancestry in a series of 91 Brazilian CRC patients. Driver mutations were found in the APC (71.4%)...


Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

Pertesi, Maroulio; Vallée, Maxime; Wei, Xiaomu; Revuelta, Maria V.; Galia, Perrine; Demangel, Delphine; Oliver, Javier; Foll, Matthieu; Chen, Siwei

[Excerpt] Multiple myeloma (MM) is the third most common hematological malignancy, after Non-Hodgkin Lymphoma and Leukemia. MM is generally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) [1], and epidemiological studies have identified older age, male gender, family history, and MGUS as risk factors for developing MM [2]. The somatic mutational landscape of sporadic MM has been increasing...


Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 ...

Parsons, Michael T.; Tudini, Emma; Li, Hongyan; Hahnen, Eric; Wappenschmidt, Barbara; Feliubadaló, Lidia; Aalfs, Cora M.; Agata, Simona

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, f...


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