Papers by Giuseppe Castello
Cancer, 2005
We recently performed what to our knowledge is the largest survey published to date regarding cli... more We recently performed what to our knowledge is the largest survey published to date regarding clinical trials of biotherapies for solid tumors to review their content and quality. Data concerning general study characteristics, patient and disease factors, study methodology, and factors related to the completeness of reporting in 334 prospective clinical trials were collected from 5 distinguished journals between 1990 and 2002. We found a wide diversity with regard to the modalities of conducting and reporting such trials as well as the presence of some methodologic pitfalls, suggesting that the methodologic standards for the conduction and publishing of clinical trials of biotherapies should be improved. In an additional analysis, we found a statistically significant association between the high impact factor of the journal ( 5) and a positive conclusion for the study (P 0.0003). It is interesting to note that, in a multiple regressionmodel performed to analyze the correlation between impact factor and two explanatory variables of Phase II studies (high quality vs. poor quality and a positive study conclusion vs. a negative study conclusion), the only variable found to be predictive of publication in a high-impact factor journal was the positive conclusion of the study (P 0.0024). These latter findings could indicate that a positive trial regarding biologic therapies is more likely to be published in a highimpact factor journal independent of its quality. Publication bias in other medical contexts already has been found and discussed previously. We would point out that interest in biotherapies is increasing and that, in the near future, these new compounds will enrich the therapeutic possibilities of oncology. However, the considerable heterogeneity observed between trials and evidence of a publication bias might affect the reliability of the body of published data concerning biotherapies for cancer. This issue should prompt editors and reviewers to improve their strategies and methodologic tools, particularly when discussing and evaluating negative study results.
European Journal of Cancer, Sep 1, 1999
Melanoma Research, Apr 1, 2004
The aim of this work was to study the possibility of mutations in p16/CDKN2A gene of patients wit... more The aim of this work was to study the possibility of mutations in p16/CDKN2A gene of patients with melanoma and additional nonmelanoma cancers in family history. Materials and methods Genomic DNA was extracted from blood samples of patients with histologicaly confirmed melanoma, who had in family other cancer than melanoma. The entire coding region of the p16/CDKN2A gene was screened by single stranded conformation polimorphism (SSCP) analyses and direct DNA sequencing. DNA sequence alterations were confirmed by restriction enzyme digests. Results From 85 melanoma patients with known family history 35 (41%) patients have an additional unrelated cancer in family and 9 (10%) patients have two or more cancers in family. The most frequently occurred cancers were gastric cancer (n¼9) and breast cancer (n¼7). Several known polimorphisms of the tumour suppressor p16/CDKN2A gene were detected. We have found some carriers with polimorphism at position À33 (G-C), some carriers with the Ala148 Thr polimorphism at the end of the second exon and several instancies of 500 (C-G) substitution at the 3 0 untranslated portion of the gene. Conclusions It would appear that melanoma and additional unrelated cancer in family history are not to be related with mutations in tumour suppressor p16/CDKN2A gene, but the polimorphims of this gene, possible, determine the predisposition to melanoma development. Furthermore, it can be concluded that de novo germline p16/CDKN2A mutations are rare.
Clinical Immunology, Mar 1, 2010
Hepatitis C virus (HCV) infection is a worldwide health problem because of its incidence and path... more Hepatitis C virus (HCV) infection is a worldwide health problem because of its incidence and pathogenicity. It might evolve into chronic disease, cirrhosis, and/or hepatocellular carcinoma (HCC) and the outcome is mainly determined by the host immune response. For viral clearance, combined innate and adaptive immune responses are required; resolution requires a vigorous, durable, polyclonal CD4 + and CD8 + T-cell response, with an increase in virus-specific CD8 + T cells or cytotoxic T lymphocytes. Failure of efficient immune response can lead to chronic inflammation, tissue remodeling through cell growth, apoptosis and/or necrosis and induction of oxidative stress. Development of fibrosis and/or cirrhosis plus a microenvironment conducive to genomic instability mutations will promote neoplastic transformation. System governance derives from cellular (regulatory cells) and humoral (cytokines and chemokines) immune networks. Therefore, HCC pathogenesis may be a model to study the disease progression from chronic inflammation to cancer allowing design of new strategies targeting the immune response, thereby modifying disease outcome.
Journal of Translational Medicine, Nov 3, 2010
Epidemiological, preclinical and clinical studies demonstrated that chronic inflammation induced ... more Epidemiological, preclinical and clinical studies demonstrated that chronic inflammation induced by hepatitis C virus (HCV) is crucial in hepatocellular carcinogenesis. The interaction between hepatocytes and microenvironment regards virus, inflammatory and immunocompetent cells, chemo-and cyto-kines, reactive oxygen species (ROS) and nitric oxide (NO), generating cell transformation. We suggest hepatocarcinoma (HCC) as a model in which the targeting of microenvironment determine neoplastic transformation. The present review focuses on: the role of inflammation in carcinogenesis, the clinical impact of HCC and the inadequacy of the actual therapy, the chemoprevention targeting the microenvironment.
Pharmacogenomics Journal, Jun 15, 2010
Nonsteroidal anti-inflammatory drugs possess antiproliferative activities that can affect cancer ... more Nonsteroidal anti-inflammatory drugs possess antiproliferative activities that can affect cancer cells. The aim of this study was to examine the antiproliferative effects of ibuprofen on the MKN-45 cell line. Cells were treated with ibuprofen for 24, 48 or 72 h, and cell proliferation was evaluated by cell counting and [ 3 H]-thymidine incorporation. Using microarray technology, we studied changes in the gene expression profiles over time after ibuprofen treatment. Ibuprofen induced a dose-and time-dependent reduction in cell number without altering cell viability. Genes involved in the 'biological oxidation' and 'G 1 /S checkpoint' pathways were the most significantly represented at 24 h, whereas genes involved in the 'cell cycle' and 'DNA replication' pathways were represented at 48 and 72 h. Genes associated with the 'apoptosis' pathway were also significantly represented at 72 h. Modulation of the expression of p53 and p53-induced genes (CDKN1A/ p21 and GADD45), which are involved in the G 1 /S transition, suggested an effect of ibuprofen on cell-cycle progression. Using flow cytometry, we observed an early block in the G 1 phase of the cell cycle after ibuprofen treatment. In addition, P450 family transcripts were upregulated and intracellular reactive oxygen species (ROS) was increased following 12 h of ibuprofen treatment. Ibuprofen induced ROS, which resulted in cellular alterations that promoted a p53-dependent G 1 blockade. These findings suggest that ibuprofen exerts its antiproliferative actions through cell-cycle control and the induction of apoptosis. Both of these mechanisms appear to be independent of ibuprofen's anti-inflammatory effects.
Immunochemistry, May 1, 1976
The anti-p-azobenzoate antibody response was investigated in rabbits immunized according to diffe... more The anti-p-azobenzoate antibody response was investigated in rabbits immunized according to different methods. The antibody was purified from serum samples obtained at different intervals from the beginning of immunization, and was analyzed by isoelectric focusing assay in polyacrylamide gel. Quantitation of single isoelectric components was permitted by the use of 1251-trace labeled samples. A number of isoelectric bands were identified as main components in all rabbits, and their quantitative expression was followed with time. Detection of such components was easier in animals primed subcutaneously. Main components, which are also persistent for long periods of time, could be likely referred to 'dominant' cell clones. They show a restricted pI range, as compared to the whole antibody population. Results are discussed in relation to the immunization method and route.
Annals of Oncology, Apr 1, 2000
Cutaneous malignant melanoma (CMM) is reported as highly resistant to conventional cancer therapi... more Cutaneous malignant melanoma (CMM) is reported as highly resistant to conventional cancer therapies. On the other hand, CMM is one of the few human cancers to which activity of the host immune system has been largely demonstrated [1^4]. In particular, tumor-reactive CD8+ ...
Annals of Oncology, May 1, 2000
Melanoma Research, Jun 1, 2002
Dear Sirs, Two years on from reviewing adjuvant interferon (IFN) based studies for malignant mela... more Dear Sirs, Two years on from reviewing adjuvant interferon (IFN) based studies for malignant melanoma (MM) patients with high risk of recurrences 1 - stage II-III according to the American Joint Committee on Cancer (AJCC) 2 - several questions on cost-benefits still remain to ...
International Journal of Radiation Biology, 1996
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Redia-Giornale Di Zoologia, 2004
Annals of Oncology, Dec 1, 2001
Melanoma Research, Jun 1, 1997
European Journal of Cancer, Sep 1, 1999
European Journal of Cancer, Sep 1, 1997
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Papers by Giuseppe Castello