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Therapeutic resistance in melanoma and other cancers arises via irreversible genetic, and dynamic phenotypic, heterogeneity. Here, we use directed phenotype switching in melanoma to sensitize melanoma cells to lineage-specific therapy. We show that methotrexate (MTX) induces microphthalmia-associated transcription factor (MITF) expression to inhibit(More)
AIMS The gold standard for detection of Sentinel Lymph Nodes (SLN) is a combined radioisotope and blue dye breast injection, using a gamma probe (GP). A new, non-radioactive method was developed, using a tracer (Sienna+(®)) of superparamagnetic iron oxide (SPIO) nanoparticles and a manual magnetometer (SentiMag(®)) (SM). The IMAGINE study was designed to(More)
Melanoma, the most aggressive form of skin cancer, is notoriously resistant to all current modalities of cancer therapy, including to the drug methotrexate. Melanosomal sequestration and cellular exportation of methotrexate have been proposed to be important melanoma-specific mechanisms that contribute to the resistance of melanoma to methotrexate. In(More)
BACKGROUND Tumour suppressor genes are often transcriptionally silenced by promoter hypermethylation, and recent research has implicated alterations in chromatin structure as the mechanistic basis for this repression. In addition to DNA methylation, other epigenetic post-translational modifications that modulate the stability and binding of specific(More)
Cancer is as much an epigenetic disease as it is a genetic disease, and epigenetic alterations in cancer often serve as potent surrogates for genetic mutations. Because the epigenetic factors involved in the DNA damage response are regulated by multiple elements, therapies to target specific components of the epigenetic machinery can be inefficient. In(More)
INTRODUCTION A controversial aspect of breast cancer management is the use of sentinel lymph node biopsy (SLNB) in patients requiring neoadjuvant chemotherapy (NCT). This paper discusses the detection rate (DT) and false negatives (FN) of SLNB after NCT to investigate the influence of initial nodal disease and the protocols applied. METHODS Prospective(More)
Human melanoma is a significant clinical problem. As most melanoma patients relapse with lethal drug-resistant disease, understanding and preventing mechanism(s) of resistance is one of the highest priorities to improve melanoma therapy. Melanosomal sequestration and the cellular exportation of cytotoxic drugs have been proposed to be important(More)
Sir, A recent work remarks the influence of molecular lymph node assay to diagnose micrometastases in the sentinel node of intraductal carcinoma of the breast (Osako et al, 2012). In fact, the detection of small epithelial cell aggregates became much more frequent as the sentinel lymph node biopsy replaced complete axillary dissection as a method of staging(More)
AIM One-Step Nucleic Acid Amplification (OSNA) can detect isolated tumour loads in axillary lymph nodes of breast cancer patients. We investigated the predictability of the non-sentinel lymph node (SLN) metastatic involvement (MI) based on the OSNA SLN assessment in surgical invasive breast cancer. METHODS We studied surgical breast invasive carcinoma(More)
OBJECTIVES The sentinel node is defined as the node with the highest probability of being involved in the case of lymphatic spread from a tumor. Accurate identification and biopsy of this node can avoid unnecessary lymphadenectomies. The aim of this study was to determine if there are differences in the number of isolated sentinel lymph nodes in breast(More)