Solid Tumours Show Osteotropism: Mechanisms of Bone Metastases

Bone metastases are a dismal consequence of cancer, causing severe morbidity and reducing the quality of life of patients. Solid tumours such as breast, prostate, lung and kidney cancer showed a marked osteotropism dependent on the special microenvironment provided by bone. Different cellular types are involved in the formation of bone metastases, indeed bone, immune system and tumour cells interact leading to bone lesions. During the bone resorption process, there is an intense cross-talk between immune system cells and osteoclasts (OCs). In particular, T cells release factors and cytokines, which rule osteoclastogenesis, and on the other hand, OCs produce factors that act on T cells, which are mediators of the tumour growth in bone. This review will summarize the main mechanisms of action in cancer-induced bone disease with particular regard to the cross-talk among cells of bone, tumour and immune system, focusing on factors and cytokines released by osteoclast, osteoblast, tumour cells and T cells.     

Use of a portable gamma camera for guiding surgical treatment in locally advanced breast cancer in a post-neoadjuvant therapy setting

The aim of the present study was to assess the feasibility of a portable gamma camera (PGC) for guiding surgical treatment in locally advanced breast cancer (LABC) after neoadjuvant therapy (NT). Since January 2012, a PGC (Sentinella 102, ONCOVISION) has been available in our center. We planned to perform a feasibility monocentric prospective study involving 15–20 patients with LABC for assessing the diagnostic performance of this PGC after NT (Breast Cancer Surgery-S102). Before the surgical treatment and at the end of NT an injection of 99mTc-Sestamibi (100–150 MBq) was made. Conventional scintimmamography (SMM) and Sentinella 102 images were obtained from 18 patients. 10 (55.5 %) patients showed a focal uptake of tracer in the breast or lymph nodes before or after the surgical excision (on histological specimen), while 8 did not. The histological specimen concluded for a complete response to NT in 4 (22.2 %) patients and for a partial or no response to treatment in the remnant 14 subjects. The specificity and false-negative rate of the Sentinella 102 compared to SMM were 100 % for both and 38 % vs. 60 %, respectively. The global diagnostic accuracy of Sentinella 102 was: 66.7 % (95 % confidence interval: 44.88–88.44 %). The present feasibility study shows how a new nuclear imaging device can be useful in the operating theatre for guiding a radical surgery approach in patients with LABC after NT.     

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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In vitro human colonic fermentation of indigestible fraction isolated from lunch menus: impact on the gut metabolites and antioxidant capacity

The indigestible fraction (IF) isolated from three lunch menus: Modified Mexican Lunch (MM-L), Traditional Mexican Lunch (TM-L) and Alternative Mexican Lunch (AM-L), was studied in terms of antioxidant capacity (AOX) and metabolites produced through fermentation by human intestinal microbiota. IFs were isolated after withstanding in vitro gastrointestinal digestion and total soluble polyphenols (TSP), condensed tannins (CT), hydrolysable polyphenols (HP) and AOX (DPPH, FRAP) were evaluated. AOX, pH and bacterial metabolites profile changes were also monitored during in vitro colonic fermentation. Lunch menus showed differences in IF, TSP, CT and FRAP values (p<.05). TM-L had the highest TSP and CT contents (0.84 and 1.89?g/100?g DW, respectively). Changes in pH and AOX during fermentation were time-dependent and substrate-dependent (p<.05). Butyric acid production was not significantly modified by the IFs (p>.05). Fifty-seven microbiota-produced volatile compounds were detected by SPME-GC–MS. This study shows the potential effects of food habits on bacterial metabolite production.     

Oxidation of Therapeutic Proteins and Peptides: Structural and Biological Consequences

Oxidation is a common degradation pathway that affects therapeutic proteins and peptides during production, purification, formulation, transportation, storage and handling of solid and liquid preparations. In the present work we review the scientific literature about structural and biological consequences of protein/peptide oxidation. Representative examples are discussed of specific products whose oxidation has been recently studied, including monoclonal antibodies, calcitonin, granulocyte colony-stimulating factor, growth hormone, insulin, interferon alpha and beta, oxytocin and parathyroid hormone. These examples illustrate that oxidation often leads to modifications of higher-order structures, including aggregate induction, and can generate products that are pharmacokinetically different, biologically less active and/or potentially more immunogenic than their native counterpart. It is therefore crucially important during the pharmaceutical development of therapeutic proteins and peptides to comprehensively characterize oxidation products and evaluate the impact of oxidation-induced structural modifications on the biological properties of the drug.