Search results for "Metas"
showing 10 items of 1693 documents
Genetic evolution of T-cell resistance in the course of melanoma progression
2014
Abstract Purpose: CD8+ T lymphocytes can kill autologous melanoma cells, but their activity is impaired when poorly immunogenic tumor phenotypes evolve in the course of disease progression. Here, we analyzed three consecutive melanoma lesions obtained within one year of developing stage IV disease for their recognition by autologous T cells. Experimental Design: One skin (Ma-Mel-48a) and two lymph node (Ma-Mel-48b, Ma-Mel-48c) metastases were analyzed for T-cell infiltration. Melanoma cell lines established from the respective lesions were characterized, determining the T-cell–stimulatory capacity, expression of surface molecules involved in T-cell activation, and specific genetic alteratio…
Balixafortide (a CXCR4 antagonist) + eribulin in HER2-negative metastatic breast cancer (MBC): Survival outcomes of the phase I trial.
2019
2606 Background: Balixafortide (B) is a potent antagonist of the chemokine receptor CXCR4. Preclinical evidence suggests that disrupting CXCR4 dependent pathways prevents development of breast cancer metastases, enhances the cytotoxic effect of chemotherapy and immunotherapy, and counteracts tumor cell evasion of the immune system. Encouraging safety and efficacy data were published recently from the ongoing Phase 1 trial investigating B + eribulin (E) in patients with HER2 negative MBC (Pernas S. et al. Lancet Oncol. 2018; 19: 812−24). The objective response rate, median progression free survival and median overall survival (OS) for the expanded cohort (EC) and the overall efficacy popula…
Erratum: Melanoma Unknown Primary Brain Metastasis Treatment With ECHO-7 Oncolytic Virus Rigvir: A Case Report
2018
Melanoma is considered an aggressive malignancy with a tendency of forming metastasis in the brain. Less than 10% of all melanoma cases present with unknown primary tumor location. This diagnose is yet to be fully understood, because there are only theoretical assumptions about the nature of the disease. Melanoma brain metastases have many severe side effects and, unfortunately, any disease related to the brain has limited therapeutic options due to the blood–brain barrier. The course of the disease after a treatment course is complicated to predict, and it is difficult to obtain long-lasting remission. In this report, we describe a female patient with unknown primary melanoma brain metasta…
Abstract PR04: Epigenetic silencing of CDR1as drives IGF2BP3-mediated melanoma invasion and metastasis
2020
Abstract Metastasis is the primary cause of death of cancer patients. Dissecting mechanisms governing metastatic spread may uncover new biology and/or yield promising therapeutic insights. Here we investigated the role of circular RNAs (circRNAs), a class of noncoding RNAs lacking characterized functions, in metastasis, using melanoma as a model aggressive tumor. We analyzed RNA-seq of melanocytes and melanoma short-term cultures to characterize the landscape of circRNA in melanocytic cells. We observed silencing of Cerebellar Degeneration Related 1 (CDR1as), a neuronal-enriched circRNA and known regulator of the microRNA miR-7, in melanoma cell lines and short-term cultures compared to cul…
The human Lgl polarity gene, Hugl-2, induces MET and suppresses Snail tumorigenesis
2012
Lethal giant larvae proteins have key roles in regulating polarity in a variety of cell types and function as tumour suppressors. A transcriptional programme initiated by aberrant Snail expression transforms epithelial cells to potentially aggressive cancer cells. Although progress in defining the molecular determinants of this programme has been made, we have little knowledge as to how the Snail-induced phenotype can be suppressed. In our studies we identified the human lethal giant larvae homologue 2, Hugl-2, (Llgl2/Lgl2) polarity gene as downregulated by Snail. Snail binds E-boxes in the Hugl-2 promoter and represses Hugl-2 expression, whereas removal of the E-boxes releases Hugl-2 from …
Abstract LB-243: Cetuximab and Artesunate synergistically inhibit the invasion and distant metastasis of non-small cell lung cancer
2012
Abstract Cancer is a complex disease and multi step process evolving from malfunctions of molecules and their complex networks which regulate this process. The blockage of the cancer signalling network is crucial in the cancer treatment. In some cases, single drug therapy might not be comprehensive enough to inhibit the activity of secondary signals, feedback regulations and resistance to particular molecules, due to their abundant expression or activity. An understanding of these complex phenomena in cancer therapy for the benefit of patients is essential, especially since it bears the chance to establish novel concepts of combination drug therapy. In the present study, we have tried to fi…
Abstract 3940: Inactivation of the PARD3 gene is a recurrent event in lung squamous cell carcinomas and affects STAT3 activity and tumor invasiveness
2015
Abstract Correct apicobasal polarization and intercellular adhesions are essential for the appropriate development of normal epithelia. Here, we investigated the contribution of the partitioning defective 3 gene, PARD3, to the carcinogenesis of lung squamous cell carcinomas (LSCCs). Tumor-specific PARD3 alterations were found in eight per cent of the tumors, placing PARD3 among the most common tumor suppressor genes in LSCC. Some PAR3 mutant proteins prevented the formation of contacts between neighboring cells, i.e. had reduced ability to form tight junctions and actin-based protrusions. This affected subsequent downstream signaling, i.e. binding to aPKC and activation of RAC1. Further, we…
Tumoricidal activity of endothelium-derived NO and the survival of metastatic cells with high GSH and Bcl-2 levels.
2008
Metastatic spread, not primary tumor burden, is the leading cause of cancer death. Glutathione (L-gamma-glutamyl-L-cysteinyl-glycine; GSH) is the most prevalent non-protein thiol in mammalian cells, and in cancer cells is particularly relevant in regulating mutagenic mechanisms, DNA synthesis, growth, and multidrug and radiation resistance. In malignant tumors, as compared with normal tissues, that resistance associates in most cases with higher GSH levels. Interaction of metastatic cells with the vascular endothelium activates local release of proinflammatory cytokines, which act as signals promoting cancer cell adhesion, extravasation, and proliferation. A high% of metastatic cells with h…
Moguntinones--new selective inhibitors for the treatment of human colorectal cancer.
2014
Abstract 3-Indolyl and 3-azaindolyl-4-aryl maleimide derivatives, called moguntinones (MOG), have been selected for their ability to inhibit protein kinases associated with angiogenesis and induce apoptosis. Here, we characterize their mode of action and their potential clinical value in human colorectal cancer in vitro and in vivo. MOG-19 and MOG-13 were characterized in vitro using kinase, viability, and apoptosis assays in different human colon cancer (HT-29, HCT-116, Caco-2, and SW480) and normal colon cell lines (CCD-18Co, FHC, and HCoEpiC) alone or in combination with topoisomerase I inhibitors. Intracellular signaling pathways were analyzed by Western blotting. To determine their pot…
Myeloid cell heterogeneity in lung cancer: implication for immunotherapy
2020
Lung is a specialized tissue where metastases from primary lung tumors takeoff and those originating from extra-pulmonary sites land. One commonality characterizing these processes is the supportive role exerted by myeloid cells, particularly neutrophils, whose recruitment is facilitated in this tissue microenvironment. Indeed, neutrophils have important part in the pathophysiology of this organ and the key mechanisms regulating neutrophil expansion and recruitment during infection can be co-opted by tumor cells to promote growth and metastasis. Although neutrophils dominate the myeloid landscape of lung cancer other populations including macrophages, dendritic cells, mast cells, basophils …