ABSTRACT
PURPOSE: Anemia is common in oncology and negatively impacts quality of life. However, there is lack of knowledge about iron deficiency (ID) epidemiology. The aim of this study was to prospectively assess iron status in patients with locally advanced or metastatic cancer beginning chemotherapy. METHODS: In this prospective, multicenter cohort study, anemia and ID were evaluated in patients with locally advanced or metastatic solid tumors and lymphoma before starting chemotherapy. Blood samples were collected at inclusion (W0), 6 weeks (W6), and 12 weeks (W12). Prevalence was evaluated in the general population, according to tumor location and was correlated with tumor response. RESULTS: One hundred twenty-nine patients were enrolled between 2013 and 2015; 119 had solid tumors and 10 lymphomas. At W0, there were no significant difference between locations with a prevalence around 50-60% (range 47.2-70.4%) and only a trend for colorectal cancer (70.4%, P = 0.069) due to a higher prevalence of absolute ID (18.5%). Prevalence of ID+ decreased between W0 and W6 and remained stable until W12 due to the proportion of patients with ID and without anemia. However, anemia prevalence increased during W0 and W6 and remained stable to W6 from W12 due to patients with anemia but without ID. A significant correlation between tumor response and ID prevalence was found (P = 0.036). CONCLUSIONS: We confirm the high prevalence of ID and anemia in cancer patients. ID status is correlated to tumor response providing a strong rationale for iron monitoring during cancer management.
Subject(s)
Anemia, Iron-Deficiency/epidemiology , Iron Deficiencies , Iron Metabolism Disorders/epidemiology , Neoplasms/drug therapy , Neoplasms/epidemiology , Aged , Aged, 80 and over , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/chemically induced , Cohort Studies , Female , Humans , Iron Metabolism Disorders/blood , Iron Metabolism Disorders/chemically induced , Male , Middle Aged , Prevalence , Prospective Studies , Quality of LifeABSTRACT
Gliomas represent the most frequent form of primary brain tumors in adults, the prognosis of which remains extremely poor. Inactivating mutations on the tumor suppressor TP53 were proposed as a key etiological trigger of glioma development. p53 has been recently identified as a transcriptional target of parkin. Interestingly, somatic mutations on parkin have also been linked to glioma genesis. We examined the possibility that a disruption of a functional interaction between p53 and parkin could contribute to glioma development in samples devoid of somatic parkin mutations or genetic allele deletion. We show here that parkin levels inversely correlate to brain tumor grade and p53 levels in oligodendrogliomas, mixed gliomas and glioblastomas. We demonstrate that p53 levels negatively and positively correlate to bax and Bcl2 respectively, underlying a loss of p53 transcriptional activity in all types of glial tumors. Using various cell models lacking p53 or harboring either transcriptionally inactive or dominant negative p53, as well as in p53 knockout mice brain, we establish that p53 controls parkin promoter transactivation, mRNA and protein levels. Furthermore, we document an increase of parkin expression in mice brain after p53-bearing viral infection. Finally, both cancer-related p53 inactivating mutations and deletion of a consensus p53 binding sequence located on parkin promoter abolish p53-mediated control of parkin transcription, demonstrating that p53 regulates parkin transcription via its DNA binding properties. In conclusion, our work delineates a functional interplay between mutated p53 and parkin in glioma genesis that is disrupted by cancer-linked pathogenic mutations. It also allows envisioning parkin as a novel biomarker of glioma biopsies enabling to follow the progression of this type of cancers.
Subject(s)
Brain Neoplasms/metabolism , Neoplasms/metabolism , Tumor Suppressor Protein p53/genetics , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/physiology , Alleles , Animals , Binding Sites , Brain/metabolism , Brain Neoplasms/genetics , Cell Line, Tumor , DNA Mutational Analysis , Female , Gene Deletion , Gene Expression Regulation, Neoplastic , Glioblastoma/genetics , Glioblastoma/metabolism , Glioma/genetics , Glioma/metabolism , Humans , Male , Mice , Mutation , Neoplasms/genetics , Oligodendroglioma/genetics , Oligodendroglioma/metabolism , Oligonucleotide Array Sequence Analysis , Promoter Regions, Genetic , Proto-Oncogene Proteins c-bcl-2/metabolism , Transcriptional Activation , bcl-2-Associated X Protein/metabolismABSTRACT
Six cases of perforated diverticulitis are presented that needed urgency surgery. The objective is to consider our guides of diagnosis and treatment towards this pathology and to justify Hartmann's operation as the technique of choice for these cases of generalised peritonitis.
Subject(s)
Diverticulitis, Colonic/diagnosis , Intestinal Perforation/diagnosis , Aged , Anti-Bacterial Agents , Diverticulitis, Colonic/surgery , Female , Humans , Intestinal Perforation/surgery , Male , Middle Aged , Premedication , Rectum/surgeryABSTRACT
Six cases of perforated diverticulitis are presented that needed urgency surgery. The objective is to consider our guides of diagnosis and treatment towards this pathology and to justify Hartmanns operation as the technique of choice for these cases of generalised peritonitis.
ABSTRACT
Six cases of perforated diverticulitis are presented that needed urgency surgery. The objective is to consider our guides of diagnosis and treatment towards this pathology and to justify Hartmanns operation as the technique of choice for these cases of generalised peritonitis.
ABSTRACT
Actinomycosis is a chronic infectious disease, caused by an anaerobic gram positive microorganism, the actinomyces israelii. It grows by continuity toward adjacent organs, with formation of dense masses of woody tissue, producing draining abscesses and fistulae. General symptoms of this disease are fever, chills, in association with symptoms proper of each localization. The diagnosis is made when the "sulphur granules" that are characteristic of the pus of actinomycosis are found.
Subject(s)
Abdominal Muscles/surgery , Actinomycosis/surgery , Skin Diseases, Infectious/surgery , Actinomycosis/diagnosis , Actinomycosis/drug therapy , Adult , Anti-Bacterial Agents/therapeutic use , Female , Humans , Premedication , Skin Diseases, Infectious/pathologyABSTRACT
Actinomycosis is a chronic infectious disease, caused by an anaerobic gram positive microorganism, the actinomyces israelii. It grows by continuity toward adjacent organs, with formation of dense masses of woody tissue, producing draining abscesses and fistulae. General symptoms of this disease are fever, chills, in association with symptoms proper of each localization. The diagnosis is made when the [quot ]sulphur granules[quot ] that are characteristic of the pus of actinomycosis are found.