Biomedical subjects

Livia Bianchi

Publications and source records attributed to Livia Bianchi.

7 recordsLinked to original sources

PubMed2006

Endoscopic CO2 laser surgery for early glottic cancer in patients who are candidates for radiotherapy: results of a prospective nonrandomized study.

BACKGROUND: Treatment of early glottic malignancies is controversial, particularly if postoperative endoscopy shows minimal/no residual disease. METHODS: In a prospective nonrandomized study, we performed endoscopic laser surgery with curative intent in 59 patients with early glottic carcinoma presenting for radiotherapy after diagnosis elsewhere by random biopsy or cordal stripping. We analyzed outcomes and residual cancer in the specimen. RESULTS: Clinical staging elsewhere did not correspond to (usually underestimated) the pathologic stage in 60.7%. In 22%, no tumor was identified on pathologic examination. After 35.3 months (mean), 93.2% were alive with no evidence of disease. Local control was achieved in 98.3% of the patients, and 13.5% of the patients required radiotherapy. The larynx was conserved in 98.3%. CONCLUSIONS: Biopsy/stripping are best abandoned for persistent glottic lesions. A single laser endoscopic procedure provides reliable staging and definitive treatment in most cases using fewer resources. Biopsied patients presenting for treatment should be offered laser surgery as an alternative to radiotherapy.

Adult↗

PubMed2006

Anthocyanidins decrease endothelin-1 production and increase endothelial nitric oxide synthase in human endothelial cells.

Epidemiological and intervention studies correlate anthocyanin-rich beverages and a low incidence of coronary heart diseases. Since endothelin-1 (ET-1) and nitric oxide (NO) produced by endothelial NO synthase (eNOS) are vascular tension regulators secreted by endothelial cells, we studied the influence of two anthocyanidins, namely cyanidin (CY) and delphinidin (DP), on the regulation of ET-1 and eNOS in cultured human umbilical vein endothelial cells (HUVECs). Aglycon anthocyanidin forms, such as CY and DP, may be present in vivo after the first deglycosylation step occurring in the jejunum and in the liver. DP showed a major action compared to CY inducing a significant dose-dependent inhibitory effect on both protein and mRNA levels of ET-1. CY and DP both increased the protein level of eNOS, but DP showed the major effect raising eNOS protein in a dose-dependent manner. To correlate the vasoprotective effect of CY and DP with their antioxidant activity, we analysed also the antioxidant effect of anthocyanidins both in vitro and in HUVECs. In particular, we examined the effect of anthocyanidins on endothelial heme oxygenase-1 (HO-1), an inducible stress protein. In all tests, DP showed a higher antioxidant activity than CY. Finally, the antiproliferative effect induced by DP was detected in HUVECs. DP and CY differ in the number and position of hydroxyl groups in their structure; therefore, the greater biological activity by DP, compared with CY, seems to be due to the presence of the three hydroxyl groups on the B ring in the molecular structure of DP.

Anthocyanins↗

PubMed2004

Intracellular localization of the cyclin-dependent kinase inhibitor p21CDKN1A-GFP fusion protein during cell cycle arrest.

The cyclin-dependent kinase (CDK) inhibitor p21CDKN1A is known to induce cell cycle arrest by inhibiting CDK activity and by interfering with DNA replication through binding to proliferating cell nuclear antigen. Although the molecular mechanisms have been elucidated, the temporal dynamics, as well as the intracellular sites of the activity of p21 bound to cyclin/CDK complexes during cell cycle arrest, have not been fully investigated. In this study we have induced the expression of p21CDKN1A fused to green fluorescent protein (GFP) in HeLa cells, in order to visualize the intracellular localization of the inhibitor during the cell cycle arrest. We show that p21-GFP is preferentially expressed in association with cyclin E in cells arrested in G1 phase, and with cyclin A more than with cyclin B1 in cells arrested in the G2/M compartment. In addition, we show for the first time that p21-GFP colocalizes with cyclin E in the nucleolus of HeLa cells during the G1 phase arrest.

Cell Cycle↗

PubMed2004

Anthocyanins induce cell cycle perturbations and apoptosis in different human cell lines.

To investigate the mechanistic basis for the biological properties of anthocyanins, two aglycone anthocyanins [delphinidin (DY) and cyanidin (CY)] were used to examine their effects on cell cycle progression and on induction of apoptosis in human cancer cells (uterine carcinoma and colon adenocarcinoma cells) and in normal human fibroblasts. These compounds differ in the number and position of hydroxyl groups on the beta ring in the molecular structure. Cellular uptake of anthocyanins was confirmed by HPLC analysis and no metabolites were detected. The clonogenic assay showed that CY induces a dose-dependent growth inhibitory effect only in fibroblasts. This effect was confirmed by flow cytometric analysis, showing a significant reduction of cells in S phase. In contrast, DP inhibited cell growth in normal and tumour cell lines. This event is accompanied in fibroblasts by an accumulation of cells in the S phase suggesting a block in the transition from S to G2 phase. On the other hand, in tumour cell lines we observed a reduction of cells in G1 phase, paralleled by the appearance of a fraction of cells with a hypodiploid DNA content, thus demonstrating an apoptotic effect by DP. The occurrence of apoptosis induced by DP was confirmed by morphological and biochemical features, including nuclear condensation and fragmentation, annexin V staining, DNA laddering and poly(ADP-ribose) polymerase-1-proteolysis. Furthermore, the mitochondrial membrane potential of apoptotic cells after treatment with DP was significantly lost. The different effects exerted by DP as compared with CY suggest that the presence of the three hydroxyl groups on the beta ring in the molecular structure of DP may be important for its greater biological activity.

Annexin A5↗

PubMed2004

Hyperfractionated radiotherapy in locally advanced nasopharyngeal cancer. An analysis of 43 consecutive patients.

BACKGROUND: Despite numerous randomized trials suggesting a benefit of unconventional fractionation in locally advanced head and neck cancer, the role of this approach in nasopharyngeal carcinoma is debatable. Based on the current clinical experience, the authors introduced hyperfractionated irradiation in the treatment of locally advanced head and neck cancer, including nasopharyngeal tumors. The preliminary results of this treatment approach in nasopharyngeal cancer patients are presented, with special focus on the pattern of failure and toxicity. PATIENTS AND METHODS: 43 patients with nasopharyngeal cancer (stage II-IV, TNM 1997) underwent hyperfractionated irradiation. In 34 cases, radiotherapy was preceded by a median of three cycles of cisplatin-based induction chemotherapy. Irradiation was delivered using a shrinking-field technique up to a total dose of 74.4 Gy in 62 fractions of 1.2 Gy twice daily (minimum 6-h interval)/5 days/week. RESULTS: Acute toxicity of hyperfractionated radiotherapy was significant but tolerable. Mucositis proved the most common side effect (grade 3: 24 patients, grade 4: three patients). Severe late toxicity was not observed. 30 of 34 patients (88%) responded to induction chemotherapy. At 6 weeks after completion of radiotherapy, complete response was seen in 35 patients (81%), partial response in five (12%), stable disease in one, and progressive disease in two. After a median follow-up of 32 months, 18 patients (41%) developed progressive disease. Primary tumor progression was observed in three patients, and seven patients each showed regional lymph node progression and distant metastases. In one case both regional lymph node progression and distant metastases were diagnosed. The 2-year progression-free survival and overall survival rates were 58% and 84%, respectively. CONCLUSION: Hyperfractionated radiotherapy seems a feasible and active regimen in locally advanced nasopharyngeal carcinoma. Accompanying acute and late toxicity is acceptable and does not compromise delivery of the planned irradiation dose. This regimen is associated with a high local control rate; relatively high nodal and distant failure, however, call for further treatment modifications, e. g., optimization of irradiation technique and/or dose escalation as well as improved systemic therapies.

Adolescent↗

PubMed2003

Lack of molecular relationships between lipid peroxidation and mitochondrial DNA single strand breaks in isolated rat hepatocytes and mitochondria.

We investigated the molecular relationships between lipid peroxidation and mitochondrial DNA (mtDNA) single strand breaks (ssb) in isolated rat hepatocytes and mitochondria exposed to tert-butylhydroperoxide (TBH). Our results show that mtDNA ssb induced by TBH are independent of lipid peroxidation and dependent on the presence of iron and of hydroxyl free radicals. These data contribute to the definition of the mechanisms whereby mtDNA ssb are induced and provide possible molecular targets for the prevention of this kind of damage in vivo.

Journal Article↗

PubMedDate not supplied

p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but inhibits subsequent binding of DNA polymerase delta at the G1/S phase transition.

The ability of the cyclin-dependent kinase (CDK) inhibitor p21CDKN1A to interact with PCNA recruited to DNA replication sites was investigated to elucidate the relevance of this interaction in cell cycle arrest. To this end, expression of p21 protein fused to green fluorescent protein (GFP) was induced in HeLa cells. G1 phase cell cycle arrest induced by p21GFP occurred also at the G1/S transition, as shown by cyclin A immunostaining of GFP-positive cells. Confocal microscopy analysis and co-immunoprecipitation studies showed that p21GFP co-localized and interacted with chromatin-bound PCNA and CDK2. GFP-p21 mutant forms unable to bind to PCNA (p21PCNA-) or CDK (p21CDK-) induced cell cycle arrest, although immunoprecipitation experiments showed these mutants to be unstable. Expression of HA-tagged p21wt or mutant proteins confirmed the ability of both mutants to arrest cell cycle. p21(wt)HA and p21CDK-HA, but not p21PCNA-, co-localized and co-immunoprecipitated with chromatin-bound PCNA. Association of p21 to chromatin-bound PCNA resulted in the loss of interaction with the p125 catalytic subunit of DNA polymerase delta (pol delta). These results suggest that in vivo p21 does not interfere with loading of PCNA at DNA replication sites, but prevents, or displaces subsequent binding of pol delta to PCNA at the G1/S phase transition.

CDC2-CDC28 Kinases↗