Metabolic cell communication within tumour microenvironment: models, methods and perspectives.

Environmental cues are essential in defining tumour malignancy, by promoting tumour initiation, progression and metastatic spreading. Stromal cells may metabolically cooperate or compete with cancer cells, playing a mandatory role in defining cancer metabolic plasticity, potentially dictating the final tumour outcome. Assessing shared nutrients between different tumoural or stromal compartments is essential to understand the impact of environmental nutrients on the metabolic plasticity of tumours. Here, we review analytical and computational approaches for studying the tumour metabolic microenvironment, the destiny of nutrients shared among tumour and stromal populations, as well as the molecular modules of these metabolic relationships.

Lactate modulates CD4+ T-cell polarization and induces an immunosuppressive environment, which sustains prostate carcinoma progression via TLR8/miR21 axis.

Leukocyte infiltration plays an active role in controlling tumor development. In the early stages of carcinogenesis, T cells counteract tumor growth. However, in advanced stages, cancer cells and infiltrating stromal components interfere with the immune control and instruct immune cells to support, rather than counteract, tumor malignancy, via cell-cell contact or soluble mediators. In particular, metabolites are emerging as active players in driving immunosuppression. Here we demonstrate that in a prostate cancer model lactate released by glycolytic cancer-associated fibroblasts (CAFs) acts on CD4+ T cells, shaping T-cell polarization. In particular, CAFs exposure (i) reduces the percentage of the antitumoral Th1 subset, inducing a lactate-dependent, SIRT1-mediated deacetylation/degradation of T-bet transcription factor; (ii) increases Treg cells, driving naive T cells polarization, through a lactate-based NF-kB activation and FoxP3 expression. In turn, this metabolic-based CAF-immunomodulated environment exerts a pro-invasive effect on prostate cancer cells, by activating a previously unexplored miR21/TLR8 axis that sustains cancer malignancy.

Regional cerebral blood flow and comorbid diagnosis in abstinent opioid addicts.

Studies using single photon emission computed tomography (SPECT) have found low cerebral blood flow (CBF) in frontal and parietal cortices in patients with chronic opiate dependence. In the present study, SPECT with 99mTc-HMPAO as tracer was used to compare 27 detoxified opiate addicts with nine healthy control subjects. All the subjects were evaluated with clinical psychiatric (DSM-IV), psychometric and neuropsychological measures. Compared with normal control subjects, the addicts showed a non-significant reduction of whole brain perfusion values. Significant hypoperfusion in the right frontal and left temporal lobes was found in addicts with comorbid depression, and a significant decrease in CBF in the right frontal lobe was observed in those with antisocial tendencies. A significant negative correlation emerged between Depression subscale scores on the Minnesota Multiphasic Personality Inventory and left temporal CBF in the patients. No significant correlations were found, however, between measures of cognition and CBF in opiate addicts. The asymmetrical findings in CBF that characterized the addicts relative to normal control subjects may be more closely related to mood and behavioral traits than to substance abuse, per se.

[Diabetes insipidus after selective pituitary adenomectomy. A case with late appearance]. / Diabete insipido post-adenomectomia selettiva ipofisaria. Un caso ad insorgenza tardiva.

Diabetes insipidus is a well-known complication of hypophyseal surgery. The case is described of a women presenting with evident polyuropolydipsic syndrome arising 9 years after transphenoidal hypophyseal adenectomy. The diagnosis insipidus diabetes was secondary to intrasellar scars revealed by a hypophyseal CAT scan. The unusually long interval between surgery and the onset of the syndrome is emphasised.