The expression of the anti-apoptotic protein BAG3 is induced in several cell types by exposure to high temperature, oxidants, and other stressful agents. We investigated whether exposure to 50 Hz electromagnetic fields raised BAG3 levels in the human melanoma cell line M14, in vitro and in orthotopic xenografts. Exposure of cultured cells or xenografts for 6 h or 4 weeks, respectively, produced a significant (P < 0.01) increase in BAG3 protein amounts. Interestingly, at the same times, we could not detect any significant variation in the levels of HSP70/72 protein or cell apoptosis. These results confirm the stressful effect of exposure to ELF in human cells, by identifying BAG3 protein as a marker of ELF-induced stress. Furthermore, they suggest that BAG3 induction by ELF may contribute to melanoma cell survival and/or resistance to therapy.

Human leukemia results from multiple mutations that lead to abnormalities in the expressions and functions of genes that maintain the delicate balance between proliferation, differentiation and apoptosis. Continued research on the molecular aspects of leukemia cells has resulted in the developments of several potentially useful therapeutic agents. Discovery of new cellular and/or molecular pathways enabling innate or acquired resistance of cancers to current chemotherapeutics to be overcome is therefore of crucial importance if one wants to efficiently combat those cancers associated with dismal prognoses. In this concern, natural compounds are regarded as new chemical entities for the development of drugs against various pharmacological targets, including cancer, and, above all, leukemia.

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with neuroendocrine differentiation (1-4). Most MCC affect the skin of the head and neck, often the periorbital region and the extremities; less than 10% affect the trunk or mucus membranes (1-5); regional lymph nodal metastases occur in 50 - 66% of the cases.\ud In 1992, Eusebi et al (5) described eight cases of nodal MCC in the absence of primary skin tumours or any other localization. Afterwards other authors (3,4) reported cases of “primary” nodal MCC pointing out the question if it really exists or represents, instead, metastasis from an occult neoplasm (3,4). In these cases strict clinical and instrumental criteria should be applied to perform the diagnosis of primary nodal MCC (2); likewise it is difficult to diagnose these “ectopic” tumours as MCC due to their similarity to other poorly differentiated small cell neoplasms. Therefore a specific immunohistochemical (IHC) has to be demonstrated, namely coexistence of both neuroendocrine and epithelial features, this latter with typical dot-like pattern (1-5). We report a case of recurring MCC in two distinct lymph nodal sites in absence of any evidence of primary tumor. \ud A 77-year-old male underwent to excision of a 35 X 27 mm large, right inguinal node. Histologically the node was replaced by diffuse infiltration of undifferentiated neoplasm. The tumor showed a roughly solid pattern, the cells were monomorphic, small and round with ovoid vesicular nuclei and scanty cytoplasm (fig. 1A); mitoses were frequent. ICC showed positivity for cytokeratin AE1/AE3 pattern, positivity for NSE, cromogranin and cytokeratin 20 with paranuclear-dots (fig. 1B) and negativity for LCA, cytokeratin 7 and TdT. Being negative all the clinical and instrumental investigations, including a PET-CT, a diagnosis of nodal MCC was performed. The patient received local radiotherapy (45 Gy) and was disease-free for 4 years when a routine ultrasound examination revealed a right axillary 35 x 28 mm node. The patient underwent to fine-needle cytology (FNC); the smears showed a dispersed cell population consisting of small cells with scanty and clear cytoplasm; the nuclei were round or polygonal with fine chromatin and inconspicuous nucleoli (fig. 1C). Immunocytochemistry, performed on cell block, showed a phenotype similar to that one observed in the former histological sample: NSE, CD56, CK AE1/AE3 and CK20 positivity, this latter with a dot-like pattern (Fig. 1D) and LCA, CK7 and TTF1 negativity; therefore a cytological diagnosis of nodal MCC was made. Again a careful investigation did not demonstrate any extra nodal site of origin; the patient underwent to the same former therapeutic procedure and after 8 months he is alive and free from disease.\ud In conclusion, being Merkel cells or their precursors absent in normal lymph nodes (2), in case of primary nodal MCC the presence of an occult and/or regressed primary MCC is still the most reliable hypothesis. Nonetheless the peculiar clinico-pathological presentation of our ca...

The recent introduction of pemetrexed in the first-line and maintenance treatment of advanced non-squamous NSCLC represents, in our opinion, a significant step forward in the treatment of this disease in the last 3 years. Furthermore, cisplatin plus pemetrexed has a more favorable safety profile as compared with those of pre-existing cisplatin-based regimens.

Lung cancer is the most common cancer in the world. One third of patients with non-small cell lung cancer (NSCLC) are diagnosed with locally or regionally advanced unresectable disease at presentation. Currently, in this stage of disease, a combination of chemotherapy and radiotherapy is the standard treatment approach for patients with good performance status, and concomitant chemo-radiotherapy has demonstrated to be the best therapeutic approach. However, despite improvements in treatment, local tumor control remains suboptimal and distant metastases remain the major site of failure. The diversity of molecular abnormalities in NSCLC may partly contribute to its resistance to therapy. It is therefore widely accepted that one approach to improve the efficacy of cancer therapy is the development of rational combinations of anticancer agents that may exhibit synergistic interactions. The introduction of several biologic agents represents an important advance in the management of NSCLC and some of them have shown to have a synergistic effect when given in combination with radiotherapy and chemotherapy in preclinical and in clinical models. In the present review we discuss the rationale and the feasibility of these combinations and the first results available from clinical trials.