Biomedical subjects

Paola Bonginelli

Publications and source records attributed to Paola Bonginelli.

6 recordsLinked to original sources

PubMed2006

Trastuzumab in combination with gemcitabine and vinorelbine as second-line therapy for HER-2/neu overexpressing metastatic breast cancer.

The aim of this study was to evaluate the safety and efficacy of combined treatment with trastuzumab (T), gemcitabine (gem) and vinorelbine (vin) as second-line therapy for HER-2 overexpressing metastatic breast cancer, pretreated with anthracyclines and/or taxanes and/or trastuzumab. Eligible patients had HER-2/neu-positive disease (IHC 2+ or 3+), performance status (PS) or=2 metastatic sites. Of the patients, 7 (23.3%) had received trastuzumab as first-line therapy. Treatment was well-tolerated with grade 4 neutropenia in 6 patients, grade 3 thrombocytopenia and grade 3 anemia in 1 patient, and grade 3 asthenia in 4 patients. Fifteen patients obtained an objective response (response rate, 50%; C.I. 95%, range, 31.3-68.7%). Among the patients with HER-2/neu 3+, the response rate was 73.3%. Noteworthy were 4 objective responses observed in patients with brain metastasis. Also, 7 patients had stable disease (23.3%). Median progression-free survival was 7 months (range 5-10), and median overall survival was 15 months (range 5-33). T-gem-vin is a safe and active regimen in this subgroup of patients with poor prognosis, and the efficacy of such a schedule was particularly satisfactory in patients with HercepTest 3+.

Adult↗

PubMed2004

Antiangiogenic strategies, compounds, and early clinical results in breast cancer.

Angiogenesis is a multi-step process leading to the formation of new blood vessels from pre-existing vasculature and it is necessary for primary tumor growth, invasiveness and development of metastasis. Experimental and clinical data demonstrated that breast cancer is an angiogenesis-dependent disease and that the vascular endothelial growth factor (VEGF) family plays a key role it being a highly expressed and selective endothelial cell growth factor. Preclinical studies have shown that the angiogenic switch occurs early in the multistage process of breast cancer development. Targeting the molecular pathways involved in tumor progression by biologically-designed treatments is a new therapeutic paradigm aimed to reach cancer growth control. A number of possible therapeutic targets for antiangiogenic agents have been identified. Here we discuss the therapeutic approach based on inhibition of angiogenesis in the context of breast cancer with a focus on the early clinical studies on antiangiogenic agents in advanced disease.

Angiogenesis Inhibitors↗

PubMed2003

Ex vivo screening for immunodominant viral epitopes by quantitative real time polymerase chain reaction (qRT-PCR).

The identification and characterization of viral epitopes across the Human Leukocyte Antigen (HLA) polymorphism is critical for the development of actives-specific or adoptive immunotherapy of virally-mediated diseases. This work investigates whether cytokine mRNA transcripts could be used to identify epitope-specific HLA-restricted memory T lymphocytes reactivity directly in fresh peripheral blood mononuclear cells (PBMCs) from viral-seropositive individuals in response to ex vivo antigen recall. PBMCs from HLA-A*0201 healthy donors, seropositive for Cytomegalovirus (CMV) and Influenza (Flu), were exposed for different periods and at different cell concentrations to the HLA-A*0201-restricted viral FluM158-66 and CMVpp65495-503 peptides. Quantitative real time PCR (qRT-PCR) was employed to evaluate memory T lymphocyte immune reactivation by measuring the production of mRNA encoding four cytokines: Interferon-gamma (IFN-gamma), Interleukin-2 (IL-2), Interleukin-4 (IL-4), and Interleukin-10 (IL-10). We could characterize cytokine expression kinetics that illustrated how cytokine mRNA levels could be used as ex vivo indicators of T cell reactivity. Particularly, IFN-gamma mRNA transcripts could be consistently detected within 3 to 12 hours of short-term stimulation in levels sufficient to screen for HLA-restricted viral immune responses in seropositive subjects. This strategy will enhance the efficiency of the identification of viral epitopes independently of the individual HLA phenotype and could be used to follow the intensity of immune responses during disease progression or in response to in vivo antigen-specific immunization.

Journal Article↗

PubMed2002

[Innovative treatment in oncology].

The improved knowledge of the key molecular mechanisms involved in cell transformation and tumor progression allows to the identification of new therapeutic targets for anticancer therapy. Several molecular-targeting compounds have been developed, capable to selectively interfire with tumorangiogenesis, receptors with tyrosin-chinase activity, specific tumor growth factors. A rationale selection of the patients as well as an appropriate monitoring of pharmacodynamics effects of molecular-targeting compounds need of the availability of surrogate markers, assessable in tumor tissue of circulating blood.

Antibodies, Monoclonal↗

PubMedDate not supplied

The combination of the selective cyclooxygenase-2 inhibitor celecoxib with weekly paclitaxel is a safe and active second-line therapy for non-small cell lung cancer: a phase II study with biological correlates.

PURPOSE: The selection of effective schedules of treatment for metastatic non-small cell lung cancer still remains a challenge for the oncologist. The present multicentric phase II study was designed in order to investigate the activity and safety of the combination of weekly paclitaxel and celecoxib as second-line treatment for non-small cell lung cancer. As a secondary endpoint, the possible correlation of biomarkers with objective response was investigated in a subset of patients. PATIENTS AND METHODS: Patients with platinum-refractory non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0-2 entered the present phase II study. Paclitaxel was administered at the dose of 80 mg/m(2) i.v. weekly for 6 weeks, followed by a 2-week rest, and celecoxib, 400 mg p.o. b.i.d. administered continuously. A cycle consisted of 8 weeks of treatment. Determination of circulating vascular endothelial growth factor and interleukin 6 was performed at baseline and every two cycles. RESULTS: Fifty-eight patients were enrolled: median age, 60 years (range, 30-77 years); male/female ratio = 44/14; performance status, 0, 31 patients; 1, 25 patients; and 2, two patients. Predominant histotype was adenocarcinoma (34 cases), and most patients had at least two sites of disease. According to the intent-to-treat analysis, 14/58 objective responses (24.1%) and 24/58 (41.3%) stabilizations of disease were observed, with a median duration of 4 months (range, 2-22+ months) and 5 months (range, 1-13 months), respectively. Median time to progression and median overall survival were 5 and 11 months, respectively. One-year survival was 42.5%. The main toxicity was neuropathy (4% of grade 3). Preliminary results suggest that decrease in serum vascular endothelial growth factor level is significantly associated with clinical response. DISCUSSION: Combination of celecoxib and weekly paclitaxel is safe and active new regimen in pretreated non-small cell lung cancer. Toxicity appears not to be worsened by the addition of celecoxib. According to preliminary results, serum vascular endothelial growth factor level seems to be predictive of response, suggesting that it should be further investigated as a surrogate marker of response.

Administration, Oral↗

PubMedDate not supplied

Antiangiogenic agents.

Explore the source record for details and available documents.

Angiogenesis Inhibitors↗