Search results for "target [deuteron]"
showing 10 items of 159 documents
The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models
2014
Background:Cetuximab is the only targeted agent approved for the treatment of head and neck squamous cell carcinomas (HNSCC), but low response rates and disease progression are frequently reported. As the phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways have an important role in the pathogenesis of HNSCC, we investigated their involvement in cetuximab resistance.Methods:Different human squamous cancer cell lines sensitive or resistant to cetuximab were tested for the dual PI3K/mTOR inhibitor PF-05212384 (PKI-587), alone and in combination, both in vitro and in vivo.Results:Treatment with PKI-587 enhances sensitivity to cetuximab in vitro, even in the co…
Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors
2022
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlight…
Imaging of non-glandular superficial metastases: A comparison of xeroradiography, ultrasonography and computed tomography
1989
Between January 1983 and July 1987, 1,622 cancer patients were evaluated to outline the possible applications and limits of various investigative techniques for evaluating metastases. Seventy-three cases with superficial metastases of the dermal-hypodermal (59) layers, of the muscles (11) and of other target organs (3) were included in the study. Although non-glandular superficial metastases are a relatively rare occurrence, diagnostic imaging techniques are indicated for evaluating their extent and anatomical connections. Secondary neoplasms were studied using the imaging techniques of sonography, computed tomography and xeroradiography. The diagnostic reliability of these three techniques…
Molecular diagnosis and therapy of hepatocellular carcinoma (HCC): an emerging field for advanced technologies.
2011
Despite great progress in diagnosis and management of hepatocellular carcinoma (HCC), the exact biology of the tumor remains poorly understood overall limiting the patients' outcome. Detailed analysis and characterization of the molecular mechanisms and subsequently individual prediction of corresponding prognostic traits would revolutionize both diagnosis and treatment of HCC and is the key goal of modern personalized medicine. Over the recent years systematic approaches for the analysis of whole tumor genomes and transcriptomes as well as epigenomes became affordable tools in translational research. This includes simultaneous analyses of thousands of molecular targets using microarray-bas…
Liquid Biopsy in Cancer Patients: The Hand Lens to Investigate Tumor Evolution
2017
In recent years the treatment of cancer patients has profoundly changed due to a better comprehension of the biological processes underlying tumor development and progression. Several tumors are defined as “oncogene addicted” and this discovery has led the way to the development of target therapies that are able to specifically kill cancer cells sparing normal cells from toxicity. Nowadays treatment decision is strictly dependent on the molecular characterization of the tumor; thus the path of cancer patients’ survival is tissue dependent but this may have several limitations. Indeed a single tissue biopsy represents only a snapshot limited in time and space but we are learning that tumor e…
Molecular Diagnostics: Innovative Technologies for Clinical and Translational Research
2021
In recent years, cancer patients’ treatment has profoundly changed due to a better comprehension of the biological processes underlying tumor development and progression. Several tumors are defined as “oncogene addicted” meaning that they are strictly dependent on oncogene activation for their own survival. This discovery has indeed led the way to the development of target therapies that are able to specifically kill cancer cells sparing normal cells from toxicity. For these reasons, nowadays, treatment decision is strictly dependent on the molecular characterization of the tumor that can be achieved through different technologies. Within this chapter, we will discuss the main technologies …
Biochemical bases for a widespread tolerance of cyanobacteria to the phosphonate herbicide glyphosate
2008
Possible non-target effects of the widely used, non-selective herbicide glyphosate were examined in six cyanobacterial strains, and the basis of their resistance was investigated. All cyanobacteria showed a remarkable tolerance to the herbicide up to millimolar levels. Two of them were found to possess an insensitive form of glyphosate target, the shikimate pathway enzyme 5-enol-pyruvyl-shikimate-3-phosphate synthase. Four strains were able to use the phosphonate as the only phosphorus source. Low uptake rates were measured only under phosphorus deprivation. Experimental evidence for glyphosate metabolism was also obtained in strains apparently unable to use the phosphonate. Results suggest…
Using Y-chromosome capture enrichment to resolve haplogroup H2 shows new evidence for a two-path Neolithic expansion to Western Europe
2021
Uniparentally-inherited markers on mitochondrial DNA (mtDNA) and the non-recombining regions of the Y chromosome (NRY), have been used for the past 30 years to investigate the history of humans from a maternal and paternal perspective. Researchers have preferred mtDNA due to its abundance in the cells, and comparatively high substitution rate. Conversely, the NRY is less susceptible to back mutations and saturation, and is potentially more informative than mtDNA owing to its longer sequence length. However, due to comparatively poor NRY coverage via shotgun sequencing, and the relatively low and biased representation of Y-chromosome variants on capture assays such as the 1240 k, ancient DNA…
Morphological abnormalities induced by Fenoxycarb on the pupa ofPhanerotoma (Phanerotoma) ocularisKohl (Hym., Braconidae)
1993
Fenoxycarb at concentrations of 0.001 μg/ml, 0.005 μg/ml, 0.01 μg/ml, 0.05μg/ml and 0.1 μg/ml had an adverse effect on the pupa of Phanerotoma (Phanerotoma) ocularis. When topically applied, it induced morphological abnormalities. The percentage of anomalous obtained depended of developmental pupal stage and was higher when was applied in the first moment of development (80 %-90 %) than in the final of development (50%-60%). These anomalous was inviables. Zusammenfassung Morphologische Abnormitaten bei Puppen von Phanerotoma (Phanerotoma) ocularis Kohl (Hym., Braconidae) nach Einwirkung von Fenoxycarb Fenoxycarb, in Konzentrationen von 0.001 μg/ml, 0.0005 μg/ml, 0.01 μg/ml, 0.05 |μg/ml und …
Positron emission tomography in CNS drug discovery and drug monitoring.
2014
Molecular imaging methods such as positron emission tomography (PET) are increasingly involved in the development of new drugs. Using radioactive tracers as imaging probes, PET allows the determination of the pharmacokinetic and pharmacodynamic properties of a drug candidate, via recording target engagement, the pattern of distribution, and metabolism. Because of the noninvasive nature and quantitative end point obtainable by molecular imaging, it seems inherently suited for the examination of a pharmaceutical’s behavior in the brain. Molecular imaging, most especially PET, can therefore be a valuable tool in CNS drug research. In this Perspective, we present the basic principles of PET, th…