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.     

Slow versus standard up-titration of paroxetine for the treatment of depression in cancer patients: a pilot study

Objectives  

This study aimed to compare the tolerability and efficacy of two different titrations of paroxetine (slow and standard) in a population of cancer patients with depression.     

Targeting the “Cytokine Storm” for Therapeutic Benefit

Inflammation is the body''s first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacterium Francisella tularensis, do trigger life-threatening “cytokine storms” in the host which can result in significant pathology and ultimately death. For these diseases, it has been proposed that downregulating inflammatory immune responses may improve outcome. We review some of the current candidates for treatment of cytokine storms which may prove useful in the clinic in the future and compare them to more traditional therapeutic candidates that target the pathogen rather than the host response.     

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

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Red grape (Vitis vinifera L.) flavonoids down‐regulate collagen type III expression after UV‐A in primary human dermal blood endothelial cells

Red grape (Vitis vinifera L.) flavonoids including flavan‐3‐ols (eg, catechin and epicatechin), flavonols (eg, quercetin) and anthocyanins (eg, malvidin) exert anti‐inflammatory and antioxidant activities. In the skin they also have a photoprotective action, and their effects have been extensively investigated in keratinocytes, melanocytes and fibroblasts. Despite their known effects also on blood vasculature, little is known on their activities on human dermal blood endothelial cells (HDBECs), which are critically involved in skin homeostasis as well as in the pathogenesis of neoplastic and inflammatory skin diseases. We sought to study the biological effects of selected red grape flavonoids in preventing the consequences of ultraviolet (UV)‐A irradiation in vitro. Our results show that red grape flavonoids prevent UV‐A‐induced sICAM‐1 release in HDBECs, suggesting that this cell type could represent an additional target of the anti‐inflammatory activity of flavonoids. In addition, flavonoids effectively inhibited UV‐A‐induced synthesis of collagen type III at both RNA and protein level, indicating that dermal blood microvasculature could be actively involved in ECM remodelling as a consequence of skin photo‐ageing, and that this can be prevented by red grape flavonoids.     

Histopathological evaluation of duodenal biopsy in the PreventCD project. An observational interobserver agreement study

Aim of the current study was to evaluate the inter‐observer agreement between pathologists in the diagnosis of celiac disease (CD), in the qualified context of a multicenter study. Biopsies from the “PreventCD” study, a multinational‐ prospective‐ randomized study in children with at least one‐first‐degree relative with CD and positive for HLA‐DQ2/HLA‐DQ8. Ninety‐eight biopsies were evaluated. Considering diagnostic samples with villous atrophy (VA), the agreement was satisfactory (κ = 0.84), but much less when assessing the severity of these lesions. The use of the recently proposed Corazza‐Villanacci classification showed a moderately higher level of agreement (κ = 0.39) than using the Marsh‐Oberhuber system (κ = 0.31). 57.1% of cases were considered correctly oriented. A number of >4 samples per patient was statistically associated to a better agreement; orientation did not impact on κ values. Agreement results in this study appear more satisfactory than in previous papers and this is justified by the involvement of centers with experience in CD diagnosis and by the well‐controlled setting. Despite this, the reproducibility was far from optimal with a poor agreement in grading the severity of VA. Our results stress the need of a minimum of four samples to be assessed by the pathologist.