Residential Radon and Risk of Lung Cancer in an Italian Alpine Area

To evaluate whether residential radon exposure explains the excess mortality for lung cancer in an Italian alpine valley with high natural radioactivity, the authors conducted a population-based case-control study on 138 deceased cases and 291 sex- and year-of-birth-matched controls. Year-long alpha-track measurements of radon were performed in the most recent residence, and information about occupational history and lifetime smoking habits was obtained. The authors adjusted for smoking, and radon was associated with lung cancer risk among men: compared with a radon level of < 40 becquerels (Bq) per cubic meter (m³), the odds ratios for 40–76 Bq/m³, 77–139 Bq/m³, 140–199 Bq/m³, and 200+ Bq/m³ were 2.1, 2.0, 2.7, and 1.4, respectively. The association between radon and lung cancer, as determined with a multiplicative model, was found only among male smokers.     

Metachronous tumor development in unilateral retinoblastoma

PURPOSE: A series of 205 retinoblastoma (RB) patients referred to the Department of Ophthalmology at the University of Siena (Italy) was evaluated in order to assess the proportion of unilateral cases later developing tumors in the companion eye ("metachronous" bilateral retinobastoma) (MBRB). METHODS: The total number of unilaterally affected patients developing tumors in the fellow eye was recorded and the risk factors assessed for the development of asynchronous bilateral retinoblastoma, i.e., family history, tumor multifocality and early age at diagnosis. RESULTS: Only two out of 133 (1.5%) unilateral retinoblastoma patients in our series could be considered affected by MBRB. CONCLUSIONS: The incidence of MBRB in our series was negligible (1.5% of all unilateral cases) compared to other reports. None of the reported risk factors for the development of tumors in the fellow eye was relevant in the present series. Although close follow-up of some unilateral cases is still recommended, thorough examination of the fellow eye, to search for lesions in the peripheral retina, is essential in all cases of unilateral RB. MBRB may be a distinctive clinical entity with specific clinical, genetic and prognostic features. However, all these aspects need to be better investigated in larger series.     

Allogeneic tumor-dendritic cell fusion vaccines for generation of broad prostate cancer T-cell responses

Antigen-loaded dendritic cells (DC) are considered potent stimulators of protective immunity. In some studies, DC hybridized with tumor cells have shown promising antitumor responses in mice as well as in humans. A practical drawback of this approach is the limited availability of autologous tumor samples. We investigated the possibility of hybridizing allogeneic prostate cancer cells with human-monocyte-derived DC, and thereby combine the wide repertoire of antigens from the tumor cells with the costimulatory features of the autologous antigen-presenting cells. Three tumor cell lines were used for hybridization using polyethylene glycol (PEG). We show that all three cell lines formed hybrids with DC to the same extent and without significant loss of viability. Restimulation of autologous T cells with these hybrids resulted in generation of tumor-specific IFNγ-producing T cells with all three tumor cell lines. Similar tumor specificity could not be obtained if T cells were stimulated using a mixture of non-PEG-fused tumor cells and DC. Moreover, these T cells were capable of specific recognition of other tumor cells of prostate cancer origin and autologous DC pulsed with lysate from these prostate cancer cell lines, while a panel of unrelated EBV-transformed B cell lines were not recognized. These results are strongly indicative of the true tumor specificity of these T cells. Our results suggest that DC hybridized with allogeneic prostate cancer cell lines are potent stimulators of a broad prostate-tumor-specific response.     

Primers and protocols for standardized detection of minimal residual disease in acute lymphoblastic leukemia using immunoglobulin and T cell receptor gene rearrangements and TAL1 deletions as PCR targets: report of the BIOMED-1 CONCERTED ACTION: investigation of minimal residual disease in acute leukemia.

It is now widely accepted that the detection of minimal residual disease (MRD) has prognostic value in acute leukemia. However clinical MRD studies need standardized techniques. Therefore, several European laboratories have aligned their goals and performed comparative studies to achieve optimization and standardization of MRD techniques. This was achieved via the BIOMED-1 Concerted Action "Investigation of minimal residual disease in acute leukemia: International standardization and clinical evaluation." This report describes the development of PCR primers and protocols for the detection of MRD in acute lymphoblastic leukemia (ALL) using clone-specific junctional regions of immunoglobulin and T cell receptor gene rearrangements and TAL1 deletions as PCR targets. A total of 54 primers was developed (1) to amplify rearrangements of the TCRD, TCRG, and IGK (Kde) genes as well as TAL1 deletions; (2) to sequence the junctional regions and breakpoint fusion regions; and (3) to perform MRD detection in bone marrow or peripheral blood samples during follow-up of ALL patients. Protocols were established to identify PCR targets at diagnosis by performing 25 PCR reactions per patient using appropriate positive and negative controls. Standardized protocols were developed for MRD monitoring via single amplification of the PCR target followed by dot blot hybridization with the corresponding patient-specific junctional region probe. In addition, alternative approaches were designed for cases where the target sensitivity of at least 10(-4) was not obtained. The standardization described here of MRD-PCR techniques is essential for the process of translating MRD research into clinical practice.     

Serum interferon (IFN)-neutralizing antibodies and bioactivities of IFNs in patients with severe type II essential mixed cryoglobulinemia

The efficacy of alpha interferon (IFN-alpha) in the treatment of severe type II essential mixed cryoglobulinemia (EMC) has been reported previously. In some patients, the development of neutralizing antibodies to recombinant IFN-alpha (rIFN-alpha) can affect the clinical response achieved with rIFN-alpha; a second treatment with natural IFN-alpha preparations may reinduce the clinical response. In the present study the ability of leukocyte IFN (LeIFN) to restore the response was investigated from a pharmacodynamic viewpoint. Specifically, the pharmacodynamic profiles of different IFN-alpha preparations were studied by measuring the serum neopterin levels and the levels of expression of protein MxA mRNA in in vivo peripheral blood mononuclear cells in two patients with EMC whose resistance to rIFN-alpha2a treatment increased concomitantly with the development of neutralizing antibodies. These markers were measured before injection and at 24 and 48 h after a single injection of rIFN-alpha2a, consensus IFN [(C)IFN], or LeIFN. No increase or only a slight increase in MxA mRNA levels was detectable after administration of rIFN-alpha2a or (C)IFN, whereas a significant increase (>/=10-fold) in MxA mRNA expression was recorded following administration of LeIFN. The neutralizing antibodies to rIFN-alpha2a cross-react with (C)IFN. Sera from these patients neutralized most but not all of the subtypes present in the natural IFN-alpha (LeIFN) mixture, and no significant increase in neopterin levels was observed after these patients were switched to LeIFN treatment. In summary, the data demonstrate that the problem of neutralizing antibodies still exists and that LeIFN may induce an increase in the level of MxA mRNA expression but not an increase in neopterin levels in patients who are resistant to treatment with rIFN-alpha2a or (C)IFN.     

Migration, socio-economic status and the risk of colorectal cancer in Italy.

To assess how the risk of cancer of the colon and rectum relates to place of birth and socio-economic status, we analysed data from an Italian case-control study. Data included 1225 cases with a recent diagnosis of cancer of the colon (ages 19-74 years), 728 cases of cancer of the rectum (ages 23-74 years) and 4154 controls (ages 19-74 years), frequency-matched with cases by age and catchment area and admitted to hospitals for a wide spectrum of acute non-neoplastic conditions. Compared with residents born in the north of Italy, migrants from the centre and south had an odds ratio (OR) of 0.7 (95% CI 0.5-0.9) for colon cancer and OR of 0.9 (95% CI 0.7-1.2) for cancer of the rectum. The inverse association of migration with colon cancer was stronger among women (OR 0.5, 95% CI 0.4-0.8) than among men (OR 0.8, 95% CI 0.6-1.1), and was independent of education and occupation. Among migrants, the direct association between education and colon cancer risk was less clear than among non-migrants. In conclusion, place of origin played an independent role in colon cancer aetiology. Results on rectal cancer were less clear, although in the same direction. Among migrants, those less susceptible to behavioural changes (e.g. women) retained most of the benefit associated with their place of origin.     

Motor somatotopy in the striatum of rat: manipulation, biting and gait

The objective of this study was to examine the hypothesis of somatotopically organized motor functions in the striatum. In Experiment 1, ibotenate-induced lesions of the rostrolateral striatum in rats produced a transient decrease of ad libitum food intake, a more enduring decrease of body weight, and chronic impairments of food biting, holding of hard food pellets and feeding efficiency, with no apparent alterations of gait balance in a beam walking task. Lesions of the medial striatum had minimal or no reliable effects on any of the measured parameters. In Experiment 2, the motoric effects of ibotenate lesions restricted to either the dorsomedial or the dorsolateral or the ventrolateral regions of the rostral striatum were examined. Lesions of the dorsolateral striatum produced the most deleterious effect on holding postures of the forelimbs, whereas lesions of the ventrolateral striatum maximally affected food biting, feeding efficiency, ad libitum food intake, and body weight. No regional lesions affected gait balance. Dorsomedial striatal lesions did not affect any of the measured parameters. The findings support the hypothesis of a somatotopically organized role of the rostrolateral striatum in orofacial and forelimb motor control.