Management and outcome of metastatic pheochromocytomas/paragangliomas: a monocentric experience.

BACKGROUND: Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors releasing catecholamines. Metastatic pheochromocytomas/paragangliomas (PPGLs) occur in about 5-26% of cases. To date, the management of patients affected by metastatic disease is a challenge in the absence of guidelines. AIM: The aim of this study was to evaluate the overall survival (OS) and the progression-free survival (PFS) in metastatic PPGLs. METHODS: Clinical data of 20 patients referred to the Careggi University Hospital (Florence, Italy) were retrospectively collected. Follow-up ranged from 1989 to 2019. Site and size of primary tumor, biochemical activity, genetic analysis and employed therapies were considered. Data were analyzed with SPSS version 27. RESULTS: Nine PHEOs (45%) and 11 PGLs (55%) were enrolled. Median age at diagnosis was 43.5 years [30-55]. Mean follow-up was 104.6 ± 89.3 months. Catecholamines were released in 70% of cases. An inherited disease was reported in 50% of patients. OS from the initial diagnosis (OSpt) and from the metastatic appearance (OSmtx) were lower in older patients (OSpt p = 0.028; OSmtx p < 0.001), abdominal PGLs (OSpt p = 0.007; OSmtx p = 0.041), larger tumors (OSpt p = 0.008; OSmtx p = 0.025) and sporadic disease (OSpt p = 0.013; OSmtx p = 0.008). CONCLUSION: Our data showed that older age at the initial diagnosis, sympathetic extra-adrenal localization, larger tumors and wild-type neoplasms are related to worse prognosis. Notably, the employed therapies do not seem to influence the survival of our patients. At present, effective treatments for metastatic PPGLs are missing and a multidisciplinary approach is indispensably required.

Giant dipole resonance in the hot and thermalized 132Ce nucleus: damping of collective modes at finite temperature.

The gamma decay of the giant dipole resonance (GDR) in the 132Ce compound nucleus with temperature up to approximately 4 MeV has been measured, using the reaction 64Ni + 68Zn at E(beam) = 300, 400, and 500 MeV. The gamma and charged particles measured in coincidence with recoils are consistent with a fully equilibrated compound nucleus emission. The GDR width, obtained with the statistical model analysis, is found to increase almost linearly with temperature. This increase is rather well reproduced within a model including thermal shape fluctuations and the lifetime of the compound nucleus.

Strong enhancement of extremely energetic proton production in central heavy ion collisions at intermediate energy.

The energetic proton emission has been investigated as a function of the reaction centrality for the system (58)Ni + (58)Ni at 30A MeV. Extremely energetic protons (E(NN)(p) > or = 130 MeV) were measured and their multiplicity is found to increase almost quadratically with the number of participant nucleons, thus indicating the onset of a mechanism beyond one- and two-body dynamics.

Nuclear detecting systems at LNL and LNS: foreseen experiments to provide basic data for heavy-ion risk assessment.

The use of existing detecting systems developed for nuclear physics studies allows collecting data on particle and ion production cross-sections in reactions induced by Oxygen and Carbon beams, of interest for hadrontherapy and heavy-ion risk assessment. The MULTICS and GARFIELD apparatus, together with the foreseen experiments, are reviewed.

Dependence of benzo(a)pyrene metabolism on NADPH pool in normal and glucose-6-phosphate dehydrogenase deficient human fibroblasts.

Human skin fibroblasts (HSF), from normal donors and donors carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase, grown in vitro in the presence of 0.25-5 microM benzo(a)pyrene (BaP), produced the following organic-soluble metabolites: 9,10-diol, 7,8-diol, quinones, 3- and 9-hydroxide and a more polar fraction, and the following water-soluble metabolites: more polar, 3- and 9-hydroxide and 9,10-diol. Single organic- and water-soluble metabolites increased with BaP concentration in both types of HSF, but the ratio normal/variant increased with BaP concentration. NADPH level and NADPH/NADP+ ratio underwent a slight decrease in normal HSF incubated with 2.5 microM BaP, while a greater fall occurred in the deficient HSF at 0.25 and 2.5 microM BaP. NADPH content seems to be rate-limiting for BaP metabolism in the deficient cells.

5-Azacytidine accelerates yeast-mycelium conversion in Candida albicans.

The effect of the DNA demethylating agent 5-azacytidine (5-azaC) on the morphological development of Candida albicans blastospores has been investigated by microscopic observations. It was found that this compound does not produce any morphogenetic effect when the cells are not induced to mycelial form. By contrast, on the induced cells, 5-azaC markedly accelerates the process of germ tube formation. In addition in the treated cells, yeast-mycelium conversion develops synchronously, whereas it is asynchronous and slow in the normal cells. These data indicate that, together with phenotypic modifications, modulation of gene activity by DNA demethylation occurs in Candida albicans during morphogenetic changes.

Aberrant development of Trichophyton mentagrophytes hyphae cultured in the presence of Congo red.

When Trichophyton mentagrophytes colonies were placed on a medium containing 150 micrograms/ml of Congo red, a dye which prevents chitin fibrillogenesis, their growth rate was reduced. The newly formed mycelium, examined under an ultraviolet microscope, consisted of thick, curled and branched hyphae endowed with swollen tips and subapical bulges. Short-time exposure revealed that the major sites of dye accumulation were the extension zones. Normally structured hyphae arose from aberrant mycelia when they were transferred onto a dye-free medium. The phenomena observed suggest that Congo red alters the wall properties of the extension zone, by inhibiting the gradual conversion of chitin chains, synthesized at the extreme tip, into microfibrils of increasing size and density.

Exocytosis in Saccharomyces cerevisiae treated with congo red.

When dividing cells of Saccharomyces cerevisiae were exposed to the polysaccharide-binding dye Congo red, the walls and septa became sites of chitin accumulation. In addition, the cytoplasm showed many vesicles that were different from those accumulating in the growing bud and from the lytic vacuoles of the untreated yeasts. To obtain information about these membranous structures, living cells were observed under phase contrast and UV light microscopes. Furthermore, ultrathin sections of Congo red-treated cells were processed by cytochemical techniques to reveal the chitin areas. Observations suggest that the aberrant vesicles were involved in a secretory process, and that pre-assembled chitin was not among the components transported to the cell periphery.

The effect of monensin on chitin synthesis in Candida albicans blastospores.

Monensin, a monovalent cation ionophore, was used to investigate some steps of the wall synthesis and morphogenesis in Candida albicans blastospores. In the presence of the drug, the pathogenic yeast developed enormous wall and septum thickenings that reacted intensely and specifically with wheat germ agglutinin and chitinase coupled to colloidal gold and fluorescein isothiocyanate. Therefore, the aberrant zones are interpreted as sites of chitin accumulation. The increased production of this homopolymer, also demonstrated by the chemical analysis of cell wall preparations, implies that monensin interferes in some way with the regulatory factors that normally control, in space and time, chitin synthetase activity.

Effects of a new pyrazolo [3, 4-d]pyrimidine on growth and morphology of Candida albicans.

A new pyrazolo [3, 4-d]pyrimidine derivative was synthesized and its antifungal activity evaluated in vitro against mycelial and yeast cells of Candida albicans. The most striking ultrastructural changes following treatment with 10-30 micrograms/ml (mycelia) and 25-75 micrograms/ml (yeasts) consisted in the deterioration of the organelle membranes and in aberrant thickenings of the cell wall. The complete disorganization of the cytoplasmic structures seemed to be the final event.

Morphological anomalies induced by Congo red in Aspergillus niger.

Aspergillus niger germ tubes were exposed for 6 h to 0.15 mg/ml of Congo red, a stain which prevents chitin microfibril assembly. The most evident alterations, detected under ultraviolet light and by transmission and scanning electron microscopy, concerned the hyphal tips which burst or, most frequently, expanded into bulges. In the latter structures, new hyphal tips appeared which, after giving rise to more or less developed hyphae, were themselves converted into new bulges. Therefore, segments derived from isotropic and polarized growth alternated in the organisms exposed to the dye. An interpretation of these abnormalities is advanced based upon the assumption that the maintainance of a regular gradient of wall viscosity in the hyphal extension zone depends primarily on the capability of glycan chains to form crystalline aggregates of increasing complexity.

Autophagic vacuole development in Trichophyton mentagrophytes exposed in vitro to miconazole.

Trichophyton mentagrophytes was treated in vitro for 24 h with an inhibitory concentration of miconazole (10(-5) M). The youngest, apical hyphal cells showed alterations of the ultrastructure of their membranes and cell wall as well as several vacuoles of an autophagic nature. Cellular autophagy appeared as a multi-step process beginning with swelling of the endoplasmic reticulum, whose membranes later fused and gave rise to large vacuoles that entrapped previously demarcated portions of the cytoplasm. Sequestered materials, initially unaltered, were ultimately degraded. The initial event in vacuolation was interpreted as entry of water into the cells, especially into the luminal space of the endoplasmic reticulum, in response to a decrease of wall pressure on the cytoplasm.