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Cell Reports. Medicine Dec 2022Homologous recombination DNA-repair deficiency (HRD) is becoming a well-recognized marker of platinum salt and polyADP-ribose polymerase inhibitor chemotherapies in...
Homologous recombination DNA-repair deficiency (HRD) is becoming a well-recognized marker of platinum salt and polyADP-ribose polymerase inhibitor chemotherapies in ovarian and breast cancers. While large-scale screening for HRD using genomic markers is logistically and economically challenging, stained tissue slides are routinely acquired in clinical practice. With the objectives of providing a robust deep-learning method for HRD prediction from tissue slides and identifying related morphological phenotypes, we first show that digital pathology workflows are sensitive to potential biases in the training set, then we propose a method to overcome the influence of these biases, and we develop an interpretation method capable of identifying complex phenotypes. Application to our carefully curated in-house dataset allows us to predict HRD with high accuracy (area under the receiver-operator characteristics curve 0.86) and to identify morphological phenotypes related to HRD. In particular, the presence of laminated fibrosis and clear tumor cells associated with HRD open new hypotheses regarding its phenotypic impact.
Topics: Humans; Deep Learning; Neoplasms; Recombinational DNA Repair; Biomarkers, Tumor
PubMed: 36516847
DOI: 10.1016/j.xcrm.2022.100872 -
Nuclear Medicine and Molecular Imaging Oct 2022Neuroblastoma (NB) is childhood's most common extracranial solid malignancy. We have compared two imaging modalities, I-MIBG and F-DOPA PET/CT, to evaluate NB. Also,...
PURPOSE
Neuroblastoma (NB) is childhood's most common extracranial solid malignancy. We have compared two imaging modalities, I-MIBG and F-DOPA PET/CT, to evaluate NB. Also, feasibility of the application of standardised scoring systems, SIOPEN and Curie scoring systems, in F-DOPA PET/CT was explored.
METHODS
Patients with histopathology-proven NB underwent I-MIBG (planar and SPECT/CT) and F-DOPA PET/CT scans, as per standard imaging protocols. Duration between scans ranged from 1 to 30 days (median = 8 days). Number of lesions in Curie and SIOPEN scoring systems applied on both modalities was compared.
RESULTS
Forty-six patients were included (M:F = 29:17) with a median age of 36 months. Both I-MIBG and F-DOPA scans were positive in 39 patients and negative in four patients. F-DOPA PET/CT was positive in additional three patients, in which I-MIBG was negative ( = 0.25). Overall, F-DOPA identified significantly greater number of lesions than I-MIBG, especially metastatic skeletal lesions ( < 0.05). Significant difference was observed between Curie scores in the two modalities, unlike SIOPEN scores. However, when the cut-off age of 18 months was taken, no significant difference was seen in either of the scoring systems in both the scans ( > 0.05). CS and SIOPEN scores were significantly higher in bone marrow-positive patients.
CONCLUSION
F-DOPA PET/CT detected more lesions than I-MIBG but had little impact on staging of the disease. For evaluation of NB, both scans can be used interchangeably as per the availability. Furthermore, both SIOPEN and Curie scoring systems, standardised for MIBG, can also be used to semi-quantify disease extent in F-DOPA PET/CT.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s13139-022-00762-6.
PubMed: 36310834
DOI: 10.1007/s13139-022-00762-6 -
Annals of Oncology : Official Journal... May 2018
Topics: Carcinoma, Hepatocellular; Cell-Free Nucleic Acids; Circulating Tumor DNA; Humans; Liver Neoplasms; Neoplastic Cells, Circulating; Pilot Projects
PubMed: 29635453
DOI: 10.1093/annonc/mdy111 -
Journal For Immunotherapy of Cancer Aug 2022High-risk neuroblastoma is a pediatric cancer with still a dismal prognosis, despite multimodal and intensive therapies. Tumor microenvironment represents a key...
BACKGROUND
High-risk neuroblastoma is a pediatric cancer with still a dismal prognosis, despite multimodal and intensive therapies. Tumor microenvironment represents a key component of the tumor ecosystem the complexity of which has to be accurately understood to define selective targeting opportunities, including immune-based therapies.
METHODS
We combined various approaches including single-cell transcriptomics to dissect the tumor microenvironment of both a transgenic mouse neuroblastoma model and a cohort of 10 biopsies from neuroblastoma patients, either at diagnosis or at relapse. Features of related cells were validated by multicolor flow cytometry and functional assays.
RESULTS
We show that the immune microenvironment of MYCN-driven mouse neuroblastoma is characterized by a low content of T cells, several phenotypes of macrophages and a population of cells expressing signatures of myeloid-derived suppressor cells (MDSCs) that are molecularly distinct from the various macrophage subsets. We document two cancer-associated fibroblasts (CAFs) subsets, one of which corresponding to CAF-S1, known to have immunosuppressive functions. Our data unravel a complex content in myeloid cells in patient tumors and further document a striking correspondence of the microenvironment populations between both mouse and human tumors. We show that mouse intratumor T cells exhibit increased expression of inhibitory receptors at the protein level. Consistently, T cells from patients are characterized by features of exhaustion, expressing inhibitory receptors and showing low expression of effector cytokines. We further functionally demonstrate that MDSCs isolated from mouse neuroblastoma have immunosuppressive properties, impairing the proliferation of T lymphocytes.
CONCLUSIONS
Our study demonstrates that neuroblastoma tumors have an immunocompromised microenvironment characterized by dysfunctional T cells and accumulation of immunosuppressive cells. Our work provides a new and precious data resource to better understand the neuroblastoma ecosystem and suggest novel therapeutic strategies, targeting both tumor cells and components of the microenvironment.
Topics: Animals; Child; Ecosystem; Humans; Mice; Neoplasm Recurrence, Local; Neuroblastoma; Transcriptome; Tumor Microenvironment
PubMed: 36054452
DOI: 10.1136/jitc-2022-004807 -
Edinburgh Medical Journal Jan 1935
PubMed: 29646766
DOI: No ID Found -
International Journal of Radiation... 2022This review is focused on radium and radionuclides in its decay chain in honor of Marie Curie, who discovered this element. (Review)
Review
PURPOSE
This review is focused on radium and radionuclides in its decay chain in honor of Marie Curie, who discovered this element.
MATERIALS AND METHODS
We conglomerated current knowledge regarding radium and its history predating our present understanding of this radionuclide.
RESULTS
An overview of the properties of radium and its dose assessment is shown followed by discussions about both the negative detrimental and positive therapeutic applications of radium with this history and its evolution reflecting current innovations in medical science.
CONCLUSIONS
We hope to remind all those who are interested in the progress of science about the vagaries of the process of scientific discovery. In addition, we raise the interesting question of whether Marie Curie's initial success was in part possible due to her tight alignment with her husband Pierre Curie who pushed the work along.
Topics: Female; France; History, 19th Century; History, 20th Century; Humans; Radiology; Radium
PubMed: 35030065
DOI: 10.1080/09553002.2022.2027542 -
National Science Review Mar 2021We propose a new approach to obtain ultra-high piezoelectric coefficients that can be infinitely large theoretically, where ferroelectrics with strain-sensitive Curie...
We propose a new approach to obtain ultra-high piezoelectric coefficients that can be infinitely large theoretically, where ferroelectrics with strain-sensitive Curie temperature are necessary. We show the first-principles plus Monte Carlo simulation evidence that many hydrogen-bonded ferroelectrics (e.g. organic PhMDA) can be ideal candidates, which are also flexible and lead-free. Owing to the specific features of hydrogen bonding, their proton hopping barrier will drastically increase with prolonged proton transfer distance, while their hydrogen-bonded network can be easily compressed or stretched due to softness of hydrogen bonds. Their barriers as well as the Curie temperature can be approximately doubled upon a tensile strain as low as 2%. Their Curie temperature can be tuned exactly to room temperature by fixing a strain in one direction, and in another direction, an unprecedented ultra-high piezoelectric coefficient of 2058 pC/N can be obtained. This value is even underestimated and can be greatly enhanced when applying a smaller strain. Aside from sensors, they can also be utilized for converting either mechanical or thermal energies into electrical energies due to high pyroelectric coefficients.
PubMed: 34691594
DOI: 10.1093/nsr/nwaa203 -
Nature Communications Feb 2024Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. Here we address...
Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. Here we address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global content in stroma increases in HGSOC after chemotherapy, the proportion of FAP CAF (also called CAF-S1) decreases. Still, maintenance of high residual CAF-S1 content after chemotherapy is associated with reduced CD8 T lymphocyte density and poor patient prognosis, emphasizing the importance of CAF-S1 reduction upon treatment. Single cell analysis, spatial transcriptomics and immunohistochemistry reveal that the content in the ECM-producing ANTXR1 CAF-S1 cluster (ECM-myCAF) is the most affected by chemotherapy. Moreover, functional assays demonstrate that ECM-myCAF isolated from HGSOC reduce CD8 T-cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, efficient inhibition after treatment of YAP1-signaling pathway in the ECM-myCAF cluster could enhance CD8 T-cell cytotoxicity. Altogether, these data pave the way for therapy targeting YAP1 in ECM-myCAF in HGSOC.
Topics: Female; Humans; Cancer-Associated Fibroblasts; Microfilament Proteins; Myofibroblasts; Ovarian Neoplasms; Ovary; Receptors, Cell Surface; Signal Transduction; Tumor Microenvironment
PubMed: 38346978
DOI: 10.1038/s41467-024-45595-3 -
Heliyon Nov 2022Spectral analysis of the pole reduced magnetic anomaly data and inversion of complete Bouguer anomaly data are employed here as there is no previous published data...
Determination of Conrad and Curie point depth relationship with the variations in lithospheric structure, geothermal gradient and heat flow beneath the central main Ethiopian rift.
Spectral analysis of the pole reduced magnetic anomaly data and inversion of complete Bouguer anomaly data are employed here as there is no previous published data regarding for the determination of the Curie point depth (CPD), Conrad depth (CD) and lithospheric mantle thickness in the central main Ethiopian rift (CMER) and its environs. The results confirm that the CPD, range between 7.68 and 20.3 km, CD, range between 16 and 25 km and lithospheric mantle thickness, range between 13.4 and 27. 8 km. These results indicate that the CMER magnetic crust occur close to the CD and lithospheric mantle thickness, but below the Moho depth beneath the study area. Based on the results on CPD, we estimate the magnitude of the geothermal gradient and heat flow in the study area. The results confirm that the geothermal gradient, range between 32.4 and 65 °C km and heat flow, range between 80 and 160 mWm. These results are found to be inversely correlated with the CPD. It is a commonly known fact that shallow CPDs generate negative magnetization. Similarly, in this study, it is recorded low magnetic anomalies overlap with shallow (less than 13.1 km) CPDs in line with high (110-160 mWm) heat flow and high (48-64 °C km) geothermal gradient values are determined to occur beneath the CMER. These results associate with the presented geotectonic and geothermal signatures of the study area.
PubMed: 36439756
DOI: 10.1016/j.heliyon.2022.e11735 -
Journal of Contemporary Brachytherapy Oct 2014In 1911, when the Nobel Foundation awarded its coveted Chemistry Prize to a 44 year old Polish born woman, it is likely they may not have expected the action ever... (Review)
Review
In 1911, when the Nobel Foundation awarded its coveted Chemistry Prize to a 44 year old Polish born woman, it is likely they may not have expected the action ever duplicated in the more than 100 years that followed. In fact, it was the second Nobel Prize in the sciences awarded to Maria Sklodowska-Curie, whom the world would come to admire, know, and love as Madame Curie. In a time of science dominated by men, the diminutive in size but larger-than-life Curie would become the first women to be awarded the prize. To this date, she remains the only person in history to win two Nobel prizes in two different science fields, and only one of four persons to win more than one. In total, Mme. Curie and her immediate family would be awarded five Nobel prizes. As astonishing as these facts may be, Mme. Curie did not seek fame nor did she seek self aggrandizement. Her whole life was one of service to humanity, an indefatigable work ethic, and humility.
PubMed: 25337133
DOI: 10.5114/jcb.2014.45133