276 research outputs found
P02.21. Short- and long-term effects of expressive writing in patients with renal cell carcinoma
915PD: Diagnosis, management, and burden of renal cell carcinomas: Results from a global patient survey in 43 countries
Selinunt, Sizilien. Forschungen in Selinunt, Teil 1. Ein neues Modell für die Stadt Selinunt. Die Feldarbeiten des Jahres 2021
Since 2021, the German Research Foundation has been funding a new interdisciplinary
field project to investigate the urban fabric of the Greek colony of Selinous in a spatially comprehensive and diachronic perspective. The project aims at extending the existing model of the ideal Greek city by considering also the historically conditioned fractures in the urban development and the multiple transformations of the living space between the 7th and 3rd century BCE. This is to be pursued by large scale archaeological, geophysical and geoarchaeological prospections, small excavations in selected areas and the thorough study of the finds and archaeobiological remains. This is a report about the first field campaigns of the various specialist disciplines and a
presentation of some preliminary results
Interferon-β gene transfer induces a strong cytotoxic bystander effect on melanoma cells
A local gene therapy scheme for the delivery of type I interferons could be an alternative for the treatment of melanoma. We evaluated the cytotoxic effects of interferon-β (IFNβ) gene lipofection on tumor cell lines derived from three human cutaneous and four canine mucosal melanomas. The cytotoxicity of human IFNβ gene lipofection resulted higher or equivalent to that of the corresponding addition of the recombinant protein (rhIFNβ) to human cells. IFNβ gene lipofection was not cytotoxic for only one canine melanoma cell line. When cultured as monolayers, three human and three canine IFNβ-lipofected melanoma cell lines displayed a remarkable bystander effect. As spheroids, the same six cell lines were sensitive to IFNβ gene transfer, two displaying a significant multicell resistance phenotype.The effects of conditioned IFNβ-lipofected canine melanoma cell culture media suggested the release of at least one soluble thermolabile cytotoxic factor that could not be detected in human melanoma cells. By using a secretion signal-free truncated human IFNβ, we showed that its intracellular expression was enough to induce cytotoxicity in two human melanoma cell lines. The lower cytoplasmatic levels of reactive oxygen species detected after intracellular IFNβ expression could be related to the resistance displayed by one human melanoma cell line. As IFNβ gene transfer was effective against most of the assayed melanomas in a way not limited by relatively low lipofection efficiencies, the clinical potential of this approach is strongly supported.Fil: Rossi, Ursula Amaranta. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gil Cardeza, Maria Lourdes. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Finocchiaro, Liliana Maria Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Glikin, Gerardo Claudio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
State of the Science: An Update on Renal Cell Carcinoma
Renal cell carcinomas (RCC) are emerging as a complex set of diseases with major socioeconomic impact and a continued rise in incidence throughout the world. As the field of urologic oncology faces these trends, several major genomic and mechanistic discoveries have altered our core understanding of this multitude of cancers, including several new rare subtypes of renal cancers. This review will examine these new findings, and place them in the context of the well-established association of clear cell RCC (ccRCC) with mutations in the von Hippel-Lindau (VHL) gene and resultant aberrant hypoxia inducible factor (HIF) signaling. The impact of novel ccRCC-associated genetic lesions on chromatin remodeling and epigenetic regulation is explored. The effects of VHL mutation on primary ciliary function, extracellular matrix homeostasis, and tumor metabolism are discussed. VHL proteostasis is reviewed, with the goal of harnessing the proteostatic machinery to refunctionalize mutant VHL. Translational efforts using molecular tools to understand discriminating features of ccRCC tumors and develop improved prognostic and predictive algorithms are presented and new therapeutics arising from the earliest molecular discoveries in ccRCC are summarized. By creating an integrated review of the key genomic and molecular biological disease characteristics of ccRCC and placing these data in the context of the evolving therapeutic landscape, we intend to facilitate interaction between basic, translational and clinical researchers involved in the treatment of this devastating disease, and accelerate progress towards its ultimate eradication
Cabozantinib versus everolimus, nivolumab, axitinib, sorafenib and best supportive care: A network meta-analysis of progression-free survival and overall survival in second line treatment of advanced renal cell carcinoma
Background
Relative effect of therapies indicated for the treatment of advanced renal cell carcinoma
(aRCC) after failure of first line treatment is currently not known. The objective of the present
study is to evaluate progression-free survival (PFS) and overall survival (OS) of cabozantinib
compared to everolimus, nivolumab, axitinib, sorafenib, and best supportive care (BSC)
in aRCC patients who progressed after previous VEGFR tyrosine-kinase inhibitor (TKI)
treatment.
Methodology & findings
Systematic literature search identified 5 studies for inclusion in this analysis. The assessment
of the proportional hazard (PH) assumption between the survival curves for different
treatment arms in the identified studies showed that survival curves in two of the studies did
not fulfil the PH assumption, making comparisons of constant hazard ratios (HRs) inappropriate.
Consequently, a parametric survival network meta-analysis model was implemented
with five families of functions being jointly fitted in a Bayesian framework to PFS, then OS,
data on all treatments. The comparison relied on data digitized from the Kaplan-Meier
curves of published studies, except for cabozantinib and its comparator everolimus where
patient level data were available. This analysis applied a Bayesian fixed-effects network
meta-analysis model to compare PFS and OS of cabozantinib versus its comparators. The
log-normal fixed-effects model displayed the best fit of data for both PFS and OS, and
showed that patients on cabozantinib had a higher probability of longer PFS and OS than
patients exposed to comparators. The survival advantage of cabozantinib increased over
time for OS. For PFS the survival advantage reached its maximum at the end of the first
year’s treatment and then decreased over time to zero.
Conclusion
With all five families of distributions, cabozantinib was superior to all its comparators with a
higher probability of longer PFS and OS during the analyzed 3 years, except with the Gompertz
model, where nivolumab was preferred after 24 months
Long-term therapy of interferon-alpha induced pulmonary arterial hypertension with different PDE-5 inhibitors: a case report
BACKGROUND: Interferon alpha2 is widely used in hepatitis and high-risk melanoma. Interferon-induced pulmonary arterial hypertension as a side effect is rare. CASE PRESENTATION: We describe a melanoma patient who developed severe pulmonary arterial hypertension 30 months after initiation of adjuvant interferon alpha2b therapy. Discontinuation of interferon did not improve pulmonary arterial hypertension. This patient could be treated successfully with phosphodiesterase-5 inhibitor therapy. CONCLUSION: This is only the 5th case of interferon-induced pulmonary arterial hypertension and the first documented case where pulmonary arterial hypertension was not reversible after termination of interferon alpha2 therapy. If interferon alpha2 treated patients develop respiratory symptoms, pulmonary arterial hypertension should be considered in the differential diagnosis. For these patients phosphodiesterase-5 inhibitors, e.g. sildenafil or vardenafil, could be an effective therapeutic approach
Serum interferon alpha receptor 2 mRNA may predict efficacy of interferon alpha with/without low-dose sorafenib for metastatic clear cell renal cell carcinoma
Variation in chromatin accessibility in human kidney cancer links H3K36 methyltransferase loss with widespread RNA processing defects
Comprehensive sequencing of human cancers has identified recurrent mutations in genes encoding chromatin regulatory proteins. For clear cell renal cell carcinoma (ccRCC), three of the five commonly mutated genes encode the chromatin regulators PBRM1, SETD2, and BAP1. How these mutations alter the chromatin landscape and transcriptional program in ccRCC or other cancers is not understood. Here, we identified alterations in chromatin organization and transcript profiles associated with mutations in chromatin regulators in a large cohort of primary human kidney tumors. By associating variation in chromatin organization with mutations in SETD2, which encodes the enzyme responsible for H3K36 trimethylation, we found that changes in chromatin accessibility occurred primarily within actively transcribed genes. This increase in chromatin accessibility was linked with widespread alterations in RNA processing, including intron retention and aberrant splicing, affecting ∼25% of all expressed genes. Furthermore, decreased nucleosome occupancy proximal to misspliced exons was observed in tumors lacking H3K36me3. These results directly link mutations in SETD2 to chromatin accessibility changes and RNA processing defects in cancer. Detecting the functional consequences of specific mutations in chromatin regulatory proteins in primary human samples could ultimately inform the therapeutic application of an emerging class of chromatin-targeted compounds
Biomarker expression patterns that correlate with high grade features in treatment naive, organ-confined prostate cancer
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