Papers by Giuseppe Castello
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
ABSTRACT
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
Melanoma Research, Feb 1, 2007
Purpose Clinical predictors for germline mutations of candidate genes in large clinic-based popul... more Purpose Clinical predictors for germline mutations of candidate genes in large clinic-based population of patients with cutaneous malignant melanoma (CMM) are widely awaited for a more accurate guidance to patients and their families about genetic testing. Methods Five ...
The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitiz... more The CXCR4/CXCL12 axis plays a role in cancer metastases, stem cell mobilization and chemosensitization. Proof of concept for efficient CXCR4 inhibition has been demonstrated in stem cell mobilization prior to autologous transplantation in hematological malignancies. Nevertheless CXCR4 inhibitors suitable for prolonged use as required for anticancer therapy are not available. To develop new CXCR4 antagonists a rational, ligand-based approach was taken, distinct from the more commonly used development strategy. A three amino acid motif (Ar-Ar-X) in CXCL12, also found in the reverse orientation (X-Ar-Ar) in the vMIP-II inhibitory chemokine formed the core of nineteen cyclic peptides evaluated for inhibition of CXCR4dependent migration, binding, P-ERK1/2-induction and calcium efflux. Peptides R, S and I were chosen for evaluation in in vivo models of lung metastases (B16-CXCR4 and KTM2 murine osteosarcoma cells) and growth of a renal cells xenograft. Peptides R, S, and T significantly reduced the association of the 12G5-CXCR4 antibody to the receptor and inhibited CXCL12induced calcium efflux. The four peptides efficiently inhibited CXCL12-dependent migration at concentrations as low as 10 nM and delayed CXCL12-mediated wound healing in PES43 human melanoma cells. Intraperitoneal treatment with peptides R, I or S drastically reduced the number of B16-CXCR4-derived lung metastases in C57/BL mice. KTM2 osteosarcoma lung metastases were also reduced in Balb/C mice following CXCR4 inhibition. All three peptides significantly inhibited subcutaneous growth of SN12C-EGFP renal cancer cells. A novel class of CXCR4 inhibitory peptides was discovered. Three peptides, R, I and S inhibited lung metastases and primary tumor growth and will be evaluated as anticancer agents.
Molecules, Jun 24, 2014
In this work, we characterized conjugated linolenic acids (e.g., punicic acid) as the major compo... more In this work, we characterized conjugated linolenic acids (e.g., punicic acid) as the major components of the hydrophilic fraction (80% aqueous methanol extract) from pomegranate (Punica granatum L.) seed oil (PSO) and evaluated their anti-inflammatory potential on some human colon (HT29 and HCT116), liver (HepG2 and Huh7), breast (MCF-7 and MDA-MB-231) and prostate (DU145) cancer lines. Our results demonstrated that punicic acid and its congeners induce a significant decrease of cell viability for two breast cell lines with a related increase of the cell cycle G 0 /G 1 phase respect to untreated cells. Moreover, the evaluation of a great panel of cytokines expressed by MCF-7 and MDA-MB-231 cells showed that the levels of VEGF and nine pro-inflammatory cytokines (IL-2, IL-6, IL-12, IL-17, IP-10, MIP-1α, MIP-1β, MCP-1 and TNF-α) decreased in a dose dependent way with increasing amounts of the hydrophilic extracts of PSO, supporting the evidence of an anti-inflammatory effect. Taken together, the data herein suggest a potential synergistic cytotoxic, anti-inflammatory and anti-oxidant role of the polar compounds from PSO.
Journal of Clinical Oncology, 2004
9584 Background: Somatic mutations of the BRAF gene has been recently reported in about two third... more 9584 Background: Somatic mutations of the BRAF gene has been recently reported in about two thirds of patients with malignant melanoma (MM). We here defined the contribution of BRAF to melanoma susceptibility, also making a comparison with the prevalence of CDKN2A germline mutations in MM patients from different geographical areas in Italy. METHODS Using a combination of DHPLC analysis and automated sequencing on genomic DNA from peripheral blood or tumor tissue samples, 569 melanoma patients (211 from North Italy and 358 from South Italy) were screened for BRAF mutations. RESULTS Three BRAF germline sequence variants (M116R, V599E, and G608H) were identified in 4/569 (0.7%) melanoma patients. High frequency (59%) of BRAF mutations was instead observed in tumor samples from cases also undergoing germline DNA analysis; at somatic level, substitution of valine 599 was found to account for majority (88%) of BRAF mutations. We then estimated the germline mutation rates in BRAF and CDKN2A among 358 consecutively-collected patients originating from South Italy; a low (2.5%) or very low (0.29%) prevalence of CDKN2A and BRAF mutations, respectively, was detected. CONCLUSIONS Our study provides a clear assessment that mutational activation of the BRAF gene is a pathogenetic event contributing to melanoma tumorigenesis at somatic level with nearly absent participation to MM predisposition at germline level. Although at lower frequency in our population, germline CDKN2A mutations have been instead demonstrated to remain the major gene involved into the melanoma susceptibility. Work was supported by Associazione Italiana Ricerca sul Cancro and Regione Autonoma Sardegna. No significant financial relationships to disclose.
European Journal of Cancer and Clinical Oncology, 1988
We studied neopterin excretion levels and immunological features of 20 patients affected by Kapos... more We studied neopterin excretion levels and immunological features of 20 patients affected by Kaposi's sarcoma (KS), compared to 30 normal controls. Eighteen patients had the classic form of Kaposi's sarcoma (CKS), while two patients were anti-human immunodejciency virus (HIV) seropositive and affected by the epidemic form associated with the acquired immunodejiciev syndrome (AIDS). In CKS patients, a trend of an increase of neopterin levels with more advanced stages appeared from our data whereas a significant reduction in CD3i-and CD4+ lymphocytes subsets was observed already at early stages (P < 0.01). CD8+ cells did not show significant variations. A significant increase in serum IgA immunoglobulins (P < 0.05) was also observed. Comparative analysis of the two patients affected by AIDS/KS showed the profound deficit in T-cell immunity but also the prognostic value of neopterin monitoring. Furthermore these hndings seem to co&n Kaposi's sarcoma as an 'opportunistic neoplasia' and indicate neopterin as a useful prognostic marker.
British journal of pharmacology, 2015
Sphingosine-1-phosphate (S1P) has been shown to be involved in the asthmatic disease as well in p... more Sphingosine-1-phosphate (S1P) has been shown to be involved in the asthmatic disease as well in preclinical mouse experimental models of this disease. The aim of this study was to understand the mechanism(s) underlying S1P effects on the lung. BALB/c, mast cell-deficient and Nude mice were injected with S1P (s.c.) on days 0 and 7. Functional, molecular and cellular studies were performed. S1P administration to BALB/c mice increased airway smooth muscle reactivity, mucus production, PGD2 , IgE, IL-4 and IL-13 release. These features were associated to a higher recruitment of mast cells to the lung. Mast cell-deficient Kit (W) (-sh/) (W) (-sh) mice injected with S1P did not display airway smooth muscle hyper-reactivity. However, lung inflammation and IgE production were still present. Treatment in vivo with the anti-CD23 antibody B3B4, which blocks IgE production, inhibited both S1P-induced airway smooth muscle reactivity in vitro and lung inflammation. S1P administration to Nude mice...
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Papers by Giuseppe Castello