Role of F-18-FDG-PET/CT in restaging of patients affected by gastrointestinal stromal tumours (GIST)

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are a subset of mesenchymal tumours that represent the most common mesenchymal neoplasms of the gastrointestinal (GI) tract and account for less than 1% of all gastrointestinal tumours. MATERIAL AND METHODS: We retrospectively evaluated 19 patients (6 females and 13 males; median age: 61 years ± 15 standard deviation) affected by GIST histologically documented after surgical intervention or biopsy. RESULTS: F18-FDG-PET/CT had identified pathologic uptakes and was considered positive for neoplastic tissue in 10 patients (53%) and negative in 9 (47%), in concordance with radiological findings. CONCLUSIONS: F18-FDG-PET/CT is a feasible, reliable, and accurate method to restage patients affected by previously histologically confirmed GIST, also in the absence of a staging study. Nuclear Med Rev 2010; 13, 2: 76–8

Primary breast non-Hodgkin lymphoma. A report of an unusual case

Although lymphomas are generally considered as tumors oflymph nodes about 25-40% arise at extranodal sites. We reporta case of a 60 years old female who developed a right breastB-diffuse large cell non-Hodgkin lymphoma in 2005 treated bychemo/radio-therapy which relapsed at the same breast in 2007and at the other breast in 2010. The patient underwent bothradiologic and nuclear medicine studies.Although lymphomas are generally considered as tumors oflymph nodes about 25-40% arise at extranodal sites. We reporta case of a 60 years old female who developed a right breastB-diffuse large cell non-Hodgkin lymphoma in 2005 treated bychemo/radio-therapy which relapsed at the same breast in 2007and at the other breast in 2010. The patient underwent bothradiologic and nuclear medicine studies

New TFR2 mutations in young Italian patients with hemochromatosis.

This work describes the identification of two subjects with young-age iron overload carrying new causative mutations in transferrin receptor-2 gene. One was compound heterozygous (Asn411del/Ala444Thr) and the second was homozygous for a mutation affecting RNA splicing (IVS17+5636G>A). Another mutation (His33Asn) and a polymorphism were found in a group of 50 controls

Human Mitochondrial Ferritin Expressed in HeLa Cells Incorporates Iron and Affects Cellular Iron Metabolism

Mitochondrial ferritin (MtF) is a newly identified ferritin encoded by an intronless gene on chromosome 5q23.1. The mature recombinant MtF has a ferroxidase center and binds iron in vitro similarly to H-ferritin. To explore the structural and functional aspects of MtF, we expressed the following forms in HeLa cells: the MtF precursor (approximately 28 kDa), a mutant MtF precursor with a mutated ferroxidase center, a truncated MtF lacking the approximately 6-kDa mitochondrial leader sequence, and a chimeric H-ferritin with this leader sequence. The experiments show that all constructs with the leader sequence were processed into approximately 22-kDa subunits that assembled into multimeric shells electrophoretically distinct from the cytosolic ferritins. Mature MtF was found in the matrix of mitochondria, where it is a homopolymer. The wild type MtF and the mitochondrially targeted H-ferritin both incorporated the (55)Fe label in vivo. The mutant MtF with an inactivated ferroxidase center did not take up iron, nor did the truncated MtF expressed transiently in cytoplasm. Increased levels of MtF both in transient and in stable transfectants resulted in a greater retention of iron as MtF in mitochondria, a decrease in the levels of cytosolic ferritins, and up-regulation of transferrin receptor. Neither effect occurred with the mutant MtF with the inactivated ferroxidase center. Our results indicate that exogenous iron is as available to mitochondrial ferritin as it is to cytosolic ferritins and that the level of MtF expression may have profound consequences for cellular iron homeostasis

A case of discrepant laboratory results in samples obtained from a central venous catheter and peripheral veins: when solving a pre-analytical mystery could improve patient care

It is now generally accepted that laboratory errors or inaccurate results are mainly due to deficiencies in the pre-analytical phase. In this report, we describe the case of a 64-year-old male affected by a relapsing follicular lymphoma, who has been treated with chemotherapy through a central venous catheter (CVC). Four different samples were collected alternatively through peripheral venipuncture and CVC sampling. Unexpectedly, the samples collected from the two different sources showed contrasting results, with the presence of unusual macrophage-like cells in the samples obtained from CVC. It was later found that the CVC was displaced into the pleural space. This case report shows how the sampling process can sometimes influence test results and how it can help clinicians identify clinical conditions that have not yet manifested

The impact of antiretroviral therapy on iron homeostasis and inflammation markers in HIV-infected patients with mild anemia

BACKGROUND: Anemia is frequent during HIV infection and is predictive of mortality. Although cART has demonstrated to reduce its prevalence, several patients still experience unresolved anemia. We aimed to characterize iron homeostasis and inflammation in HIV-infected individuals with mild anemia in relation to cART. METHODS: In this retrospective cohort study, HIV-infected patients with mild anemia, CD4+ cells > 200/mm3 at baseline, maintaining virological response for 12 months after cART starting were selected within the Standardized Management of Antiretroviral Therapy Cohort (MASTER) cohort. Several inflammation and immune activation markers and iron homeostasis indexes were measured in stored samples, obtained at cART initiation (T0) and 12 months later (T1). Patients were grouped on the basis of hemoglobin values at T1: group A (> 13 g/dl) and B (< 13 g/dl). Wilcoxon rank sum test was used to compare biomarker values. Pearson correlation coefficients were calculated for all variables. RESULTS: cART improved CD4+ and CD8+ cell counts and their ratio, but this effect was significant only in group A. Only these patients had mild iron deficiency at T0 and showed higher transferrin and lower percentage of transferrin saturation than patients of group B, but differences disappeared with cART. cART decreased inflammation in all patients, but group B had higher levels of all markers than group A, reaching statistical significance only for IL-8 values at T1 (16 vs 2.9 pg/ml; p = 0.017). Hepcidin and IL-6 levels did not show significant differences between groups. Hemoglobin levels both at T0 and T1 did not correlate with any marker. CONCLUSIONS: Baseline mild anemia in HIV-infected patients cannot always be resolved with durable efficient cART, possibly due to residual inflammation or immune activation rather than unbalanced iron homeostasis. Further research is needed on cytokine profiling to understand the mechanisms that induce anemia in HIV with suppressive cART

Analytical and clinical validation of a blood progranulin ELISA in frontotemporal dementias

OBJECTIVES: Heterozygous mutations in the granulin (GRN) gene may result in haploinsufficiency of progranulin (PGRN), which might lead to frontotemporal dementia (FTD). In this study, we aimed to perform analytical and clinical validation of a commercial progranulin kit for clinical use. METHODS: Analytical validation parameters including assay precision, selectivity, measurement range, dilution linearity, interferences and sample stability were tested according to previously described procedures. For clinical validation, PGRN levels were measured in plasma from 32 cognitively healthy individuals, 52 confirmed GRN mutation carriers, 25 C9orf72 mutation carriers and 216 patients with different neurodegenerative diseases of which 70 were confirmed as non-mutation carriers. RESULTS: Among the analytical validation parameters, assay precision and repeatability were very stable (coefficients of variation <7 %). Spike recovery was 96 %, the measurement range was 6.25-400 μg/L and dilution linearity ranged from 1:50-1:200. Hemolysis did not interfere with progranulin levels, and these were resistant to freeze/thaw cycles and storage at different temperatures. For the clinical validation, the assay was capable of distinguishing GRN mutation carriers from controls and non-GRN mutation carriers with very good sensitivity and specificity at a cut-off of 57 μg/L (97 %, 100 %, respectively). CONCLUSIONS: In this study, we demonstrate robust analytical and diagnostic performance of this commercial progranulin kit for implementation in clinical laboratory practice. This easy-to-use test allows identification of potential GRN mutation carriers, which may guide further evaluation of the patient. This assay might also be used to evaluate the effect of novel PGRN-targeting drugs and therapies

Mice lacking mitochondrial ferritin are more sensitive to doxorubicin-mediated cardiotoxicity

15noMitochondrial ferritin is a functional ferritin that localizes in themitochondria.Itisexpressedinthetestis, heart,brain,and cells with active respiratory activity. Its overexpression in culturedcellsprotectedagainstoxidativedamageandreduced cytosolic iron availability. However, no overt phenotype was describedinmicewithinactivationoftheFtMtgene.Here,we usedthe doxorubicin model ofcardiac injuryina novel strain of FtMt-null mice to investigate the antioxidant role of FtMt. These mice did not show any evident phenotype, but after acute treatment to doxorubicin, they showed enhanced mortalityandaltered heartmorphologywithfibrildisorganization and severe mitochondrial damage. Signs of mitochondrial damage were present also in mock-treated FtMt−/− mice. The hearts of saline- and doxorubicin-treated FtMt−/− mice had higher thiobarbituric acid reactive substance levels, heme oxygenase 1 expression, and protein oxidation, but did not differ from FtMt+/+ in the cardiac damage marker B-type natriureticpeptide(BNP),ATP levels, and apoptosis.However,the autophagy marker LC3 was activated. The results show that the absence of FtMt, which is highly expressed in the heart, increases the sensitivity of heart mitochondria to the toxicity of doxorubicin. This study represents the first in vivo evidence of the antioxidant role of FtMt.openopenMaccarinelli, Federica; Gammella, Elena; Asperti, Michela; Mariaregon, ; Donetti, Elena; Recalcati, Stefania; Poli, Maura; Finazzi, Dario; Arosio, Paolo; Biasiotto, Giorgio; Emiliaturco, ; Altruda, Fiorella; Lonardi, Silvia; Cornaghi, Laura; Cairo, GaetanoMaccarinelli, Federica; Gammella, Elena; Asperti, Michela; Mariaregon, ; Donetti, Elena; Recalcati, Stefania; Poli, Maura; Finazzi, Dario; Arosio, Paolo; Biasiotto, Giorgio; Emiliaturco, ; Altruda, Fiorella; Lonardi, Silvia; Cornaghi, Laura; Cairo, Gaetan