Search results for "cancers"
showing 10 items of 276 documents
Differential modulation and prognostic values of immune-escape genes in uveal melanoma
2019
Uveal melanoma (UM) is the most common primary intraocular cancer in adults. In the present study, we aimed to characterize the immunological features of primary UM cancer and to provide an association with prognostic markers and outcome. Also, we assessed the influence of the microenvironment on the expression of inhibitory immune checkpoints in UM. Genes of interest included MHC Class I and Class II molecules, as well as inhibitory immune-checkpoints, i.e. PDL1, PDL2, B7-H3, B7-H4, TBFRSF6B, CD47, CD155, GAL9, HVEM and CD200. We observed significant lower levels of MHC genes in UM cells as compared to normal uveal melanocytes. Unexpectedly however, the expression levels of most of the ana…
Characterization of Human γδ T Lymphocytes Infiltrating Primary Malignant Melanomas
2012
T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that gamma delta T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating gamma delta T cells from 74 patients with primary melanoma. We found that gamma delta T cells represent the major lymphocyte population infiltrating melanoma, and both V delta 1(+) and V delta 2(+) cells are involved. The majority of melanoma-infiltrating gamma delta cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal gamma delta T cell lines obtained from tumor-infiltrat…
Skewed Differentiation of Circulating Vγ9Vδ2 T Lymphocytes in Melanoma and Impact on Clinical Outcome
2016
OBJECTIVE:The aim of this study was to evaluate over time circulating γδ T lymphocytes in melanoma patients in terms of frequency, effector functions, and relationship with clinical stage and evolution, by comparing preoperative values to those obtained at a mean follow-up of 36 months or in the event of recurrence or disease progression, and to those of healthy controls. Also, we correlated the presence of tumor-infiltrating γδ T lymphocytes with clinical evolution of melanoma. RESULTS:Mean frequencies of circulating γδ T cells before and after melanoma removal were very similar and comparable to healthy subjects, but patients who progressed to stage III or IV showed a significantly decrea…
Willingness to pay for a cure of low-risk melanoma patients in Germany
2018
Malignant melanoma is potentially life-threatening but in most cases curable if detected early. Willingness to pay (WTP) is a preference-based construct that reflects burden of disease by assessment of the monetary value for a hypothetical cure from disease. Since WTP (directly as total amount of money) has not been assessed so far in patients with low risk melanoma, it was interesting to gain insights in this patient population and then, in a second step, compare it directly with the WTP of their treating dermato-oncologists. WTP was assessed in 125 patients with low-risk melanoma and additionally in 105 treating physicians, asking for the one-time and continuous payments they would be wil…
Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential bi…
2017
Background Malignant Pleural Mesothelioma (MPM) is an aggressive cancer mainly caused by asbestos exposure and refractory to current therapies. Specific diagnostic markers for early MPM diagnosis are needed. Changes in miRNA expression have been implicated in several diseases and cancers, including MPM. We examined if a specific miRNA signature in plasmatic extracellular vesicles (EV) may help to discriminate between malignant pleural mesothelioma patients (MPM) and subjects with Past Asbestos Exposure (PAE). Methodology/Principal findings We investigated 23 MPM patients and 19 cancer-free subjects with past asbestos exposure (PAE). We screened 754 miRNAs in plasmatic EVs by OpenArray and f…
Factors Determining Sensitivity and Resistance of Tumor Cells to Arsenic Trioxide
2012
Previously, arsenic trioxide showed impressive regression rates of acute promyelocytic leukemia. Here, we investigated molecular determinants of sensitivity and resistance of cell lines of different tumor types towards arsenic trioxide. Arsenic trioxide was the most cytotoxic compound among 8 arsenicals investigated in the NCI cell line panel. We correlated transcriptome-wide microarray-based mRNA expression to the IC(50) values for arsenic trioxide by bioinformatic approaches (COMPARE and hierarchical cluster analyses, Ingenuity signaling pathway analysis). Among the identified pathways were signaling routes for p53, integrin-linked kinase, and actin cytoskeleton. Genes from these pathways…
A modelling population-based approach to the effect of granulocyte growth factors during chemotherapy-induced neutropenia
2020
The work of this thesis is based on results of a cohort study whose main objective was to define the optimal schedule of prophylactic administration of granulocyte growth factors (G-CSF) in the context of FOLFIRINOX treatment. For this purpose, a pharmacokinetic/pharmacodynamic (PK/PD) model was built to describe the absolute neutrophil counts (ANC) time course in our population, including the three chemotherapies neutropenic effect, but also the stimulating effect of exogenous G-CSF on the proliferation and maturation of neutrophils. Based on the estimates of the model parameters, simulations were performed to determine the incidence and duration of neutropenia for each prophylactic G-CSF …
Bleomycin Exerts Ambivalent Antitumor Immune Effect by Triggering Both Immunogenic Cell Death and Proliferation of Regulatory T Cells
2013
International audience; Bleomycin (BLM) is an anticancer drug currently used for the treatment of testis cancer and Hodgkin lymphoma. This drug triggers cancer cell death via its capacity to generate radical oxygen species (ROS). However, the putative contribution of anticancer immune responses to the efficacy of BLM has not been evaluated. We make here the observation that BLM induces immunogenic cell death. In particular, BLM is able to induce ROS-mediated reticulum stress and autophagy, which result in the surface exposure of chaperones, including calreticulin and ERp57, and liberation of HMBG1 and ATP. BLM induces anti-tumor immunity which relies on calreticulin, CD8(+) T cells and inte…
The overlapping burden of the three leading causes of disability and death in sub-Saharan African children
2022
Publisher Copyright: © 2022, The Author(s). Despite substantial declines since 2000, lower respiratory infections (LRIs), diarrhoeal diseases, and malaria remain among the leading causes of nonfatal and fatal disease burden for children under 5 years of age (under 5), primarily in sub-Saharan Africa (SSA). The spatial burden of each of these diseases has been estimated subnationally across SSA, yet no prior analyses have examined the pattern of their combined burden. Here we synthesise subnational estimates of the burden of LRIs, diarrhoea, and malaria in children under-5 from 2000 to 2017 for 43 sub-Saharan countries. Some units faced a relatively equal burden from each of the three diseas…
PROX1 transcription factor controls rhabdomyosarcoma growth, stemness, myogenic properties and therapeutic targets
2022
Funding Information: ACKNOWLEDGMENTS. We would like to thank Dr. Tuomas Tammela and Dr. Monika Ehnmann for providing RMS cell lines and Dr. Jenny Högström for discussions and comments during the project. Kirsi Mattinen, Jefim Brodkin, Maxime Laird, Manon Gruchet, Ilse Paetau, Tanja Laakkonen, and Tapio Tainola are acknowledged for their excellent technical help. We also thank the Laboratory Animal Center at the University of Helsinki for expert animal care, the Biomedicum Imaging Unit for microscope support, the Biomedicum Functional Genomics Unit for the RNAseq experiments and the FIMM Technology Centre High Throughput Biomedicine for the drug sensitivity and resistance testing. Our first …