Inhibition of anaphylactic shock by gadolinium chloride-induced Kupffer cell blockade.

Data in the literature concerning the role of macrophages in anaphylaxis are contradictory. In the present study, the effect of macrophage blockade induced by gadolinium chloride (GdCl3) on anaphylactic shock is investigated. Our observations show that GdCl3 prevents lethal anaphylactic shock in mice sensitized to ovalbumin. Gadolinium chloride given i.v. in a dose of 1 mg/100 g body weight 24 or 48 h before the elicitation of anaphylactic shock resulted in 80% survival, compared with the 43% survival in the control group. The same dose of this rare-earth metal salt also greatly reduced the mortality in mice sensitized with ovalbumin containing Bordetella pertussis vaccine, and similarly abrogated the symptoms of anaphylaxis, including the accumulation of serotonin and histamine in the liver. The results suggest that macrophages play an important role in mouse anaphylaxis

Current Updates in Bleomycin-Based Electrochemotherapy for Deep-Seated Soft-Tissue Tumors

Electrochemotherapy (ECT) has evolved significantly during the last decade, expanding treatment indications from superficial skin lesions to advanced-stage, deep-seated tumors in hard-to-reach areas. Electrodes have also shown steady technological improvement throughout the years. Besides standard and VEG (variable geometry electrode) electrodes, the introduction of laparoscopic electrodes has brought on a new era in ECT treatment, making the minimally invasive approach a reality. The exact role of ECT in the oncological dashboard is yet to be determined; however, increased tumor response, pain relief, and a low number of adverse events may yield the way for more widespread application of the technique with possible further inclusion of ECT in international oncological guidelines. The aim of this review is to give an overview on the current status of ECT in deep-seated tumor treatment and shed light on its emerging role in local anticancer therapy

Detection of a rare CDKN2A intronic mutation in a Hungarian melanoma-prone family and its role in splicing regulation

The genetic predisposition to melanoma is quite heterogeneous. The major locus for melanoma predisposition is the cell cycle regulatory CDKN2A gene on chromosome 9p21 though alterations in it have been detected in only 20 40% of melanoma prone families. However, with regard to the frequency of melanoma-prone families linked to 9p21, the frequency of germline coding mutations of the CDKN2A gene is lower than expected. We set out to investigate whether the rare IVS1+37 G/C intronic mutation of the CDKN2A gene recently identified in a Hungarian melanoma prone family, influences mRNA splicing regulation. To this end, CDKN2A minigenes containing the wild type and the mutant intronic sequence were created and transfected into HeLa cells with the aim of study of the mRNA transcripts. The results revealed the emergence of a differential splicing pattern from the wild type and the mutant minigene, suggesting that this mutation may alter the splicing of CDKN2A primary mRNA and therefore might have a pathogenetic role in familial melanoma. We believe that these results confirm the importance of the identification and characterization of CDKN2A intronic mutations with a view to improvement of our understanding of the pathogenesis and the explanation of why the frequency of germline coding mutations of the CDKN2A gene is lower than expected in melanoma-prone families linked to chromosome 9p21