Biomedical subjects

Marzia Palma

Publications and source records attributed to Marzia Palma.

5 recordsLinked to original sources

PubMed2006

Clinical results of vaccine therapy for cancer: learning from history for improving the future.

Active, specific immunotherapy for cancer holds the potential of providing an approach for treating cancers, which have not been controlled by conventional therapy, with very little or no associated toxicity. Despite advances in the understanding of the immunological basis of cancer vaccine therapy as well as technological progress, clinical effectiveness of this therapy has often been frustratingly unpredictable. Hundreds of preclinical and clinical studies have been performed addressing issues related to the generation of a therapeutic immune response against tumors and exploring a diverse array of antigens, immunological adjuvants, and delivery systems for vaccinating patients against cancer. In this chapter, we have summarized a number of clinical trials performed in various cancers with focus on the clinical outcome of vaccination therapy. We have also attempted to draw objective inferences from the published data that may influence the clinical effectiveness of vaccination approaches against cancer. Collectively the data indicate that vaccine therapy is safe, and no significant autoimmune reactions are observed even on long term follow-up. The design of clinical trials have not yet been optimized, but meaningful clinical effects have been seen in B-cell malignancies, lung, prostate, colorectal cancer, and melanoma. It is also obvious that patients with limited disease or in the adjuvant settings have benefited most from this targeted therapy approach. It is imperative that future studies focus on exploring the relationship between immune and clinical responses to establish whether immune monitoring could be a reliable surrogate marker for evaluating the clinical efficacy of cancer vaccines.

Antigens, Neoplasm↗

PubMed2005

BRCA1 and BRCA2: the genetic testing and the current management options for mutation carriers.

Approximately 5-10% of breast carcinomas and 10% of ovarian carcinomas are ascribable to a genetic susceptibility. Of these, about 40% are related to genetic mutations in the genes BRCA1 and BRCA2. Despite the increasing demand for genetic testing arising from the patients and their relatives, the genetic testing can be offered yet only to individuals belonging to high-risk families in which the probability that there is a germline mutation in a BRCA gene is high and thus cancer occurrence is likely the expression of a highly penetrant genetic predisposition. In this article, we review how the current knowledge on the biological mechanisms underlying BRCA1 and BRCA2 dysfunction may contribute to the understanding of breast and ovarian cancer predisposition. The most currently employed methods for genetic testing are critically overviewed, together with some indications for the interpretation of the test outcome and the clinical management of mutation carriers.

BRCA1 Protein↗

PubMed2004

Specific role for p300/CREB-binding protein-associated factor activity in E2F1 stabilization in response to DNA damage.

E2F1, a member of the E2F family of transcription factors, plays a pivotal role in controlling both physiological cell-cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. In response to genotoxic stresses, E2F1 is stabilized by signals that include ATM-dependent phosphorylation. We recently demonstrated that DNA damage induces also E2F1 acetylation, which is required for its recruitment onto apoptotic gene promoters. Here we show that E2F1 is stabilized in response to doxorubicin and cisplatin treatments even in the absence of either ATM-dependent phosphorylation or p53 and cAbl, two major transducers of DNA damage signaling. We found that acetylation of E2F1 is, instead, required to stabilize the protein in response to doxorubicin. Finally, we report that the formation of E2F1-p300/CREB-binding protein-associated factor (P/CAF) complexes is preferentially induced in doxorubicin-treated cells, and that P/CAF acetyltransferase (HAT), but not p300 HAT activity, is required for a significant E2F1 stabilization and accumulation. Our results unveil a differential role of P/CAF and p300 in acetylation-induced stabilization of E2F1, thus supporting a specific role for P/CAF HAT activity in E2F1-dependent apoptosis in response to DNA damage.

Acetylation↗

PubMedDate not supplied

Atrial fibrillation during adjuvant chemotherapy with docetaxel: a case report.

A 46-year-old woman had an episode of atrial fibrillation during infusion of docetaxel as adjuvant chemotherapy for an infiltrating ductal carcinoma of the breast. All cardiological tests performed before treatment were normal and there was no evidence of thyroid dysfunction nor any objective or anamnestic data indicating acute or chronic cardiovascular disease. None of the drugs administered has ever shown any proarrhythmic activity. In controlled clinical trials docetaxel was found to have a very low cardiotoxicity.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Hepatic arterial continuous infusion (HACI) of oxaliplatin in patients with unresectable liver metastases from colorectal cancer.

BACKGROUND: Oxaliplatin, a new DACH-platinum compound, has provided high response rates both in untreated and 5-FU-resistant patients. AIM: To define the feasibility and toxicity profile of Oxaliplatin administered as a continuous hepatic aterial infusion. PATIENTS AND METHODS: Seventeen patients with pretreated metastatic liver colorectal cancer were treated with Oxaliplatin 20 mg/m2/day by HACI x 5 days every 3 weeks. RESULTS: Toxicity grade 3 included pain (4 out of 17), asthenia (1 out of 17) and nausea (1 out of 17). Abdominal pain grade 4 (WHO) was noted in only one patient. Overall, severe abdominal pain (main dose-limiting toxicity) was observed in 41% of patients and no chemical hepatitis and sclerosing cholangitis pain-related was proven by an endoscopic retrograde cholangiography. The response rate was not a primary end-point; nonetheless among 15 evaluable patients we observed partial responses (PR) in 7 patients (46%) and stable disease (SD) in 21% of cases for an overall tumor growth control of 67%. Progression to disease (PD) was 33%. Following chemotherapy, one patient underwent surgical removal of residual metastases, with curative intent. The 1-year survival rate was 64%. The median duration of survival was 19 months. The median delay to hepatic progression was 10 months. CONCLUSION: Further studies are required to define the role of HACI Oxaliplatin, the schedule of administration (bolus vs continuous infusion) and the combination, also in this setting, with fluoropyrimidines.

Aged↗