Showing papers by "Michele Caraglia published in 2000"
TL;DR: The combination of lanreotide with interferon had a major impact on clinical symptoms and was well tolerated and coupled with a decrease of 50% or more in serum calcitonin levels in three of seven patients.
Abstract: Somatostatin analogs are promising agents in the treatment of medullary thyroid carcinoma. We have evaluated the effects of the slow release somatostatin analog lanreotide in combination with interferon-α2b in seven patients with advanced and symptomatic medullary thyroid carcinoma. The frequency and intensity of daily flushing episodes and bowel movements, the intensity of fatigue, weight, performance status, calcitonin levels, and change in tumor masses were recorded before and during treatment. No objective complete or partial responses were recorded. However, disease stabilization and minor tumor regression were observed in three of seven and two of seven patients, respectively. The number and intensity of bowel movements and flushing episodes decreased in five of six and two of two patients, respectively. Decrease in fatigue and improvement in performance status were observed in five of seven and six of seven patients, respectively. Weight gain was recorded in three of four patients. Plasma levels of...
79 citations
TL;DR: The novel insights on the biochemical and molecular events leading to protein biosynthesis are reviewed and their involvement in cell proliferation and tumorigenesis are described and a new multimodal strategy is proposed based on the simultaneous intervention on protein synthesis and signal transduction.
Abstract: In the past years, the attention of scientists has focused mainly on the study of the genetic information and alterations that regulate eukaryotic cell proliferation and that lead to neoplastic transformation. All therapeutic strategies against cancer are, to date, directed at DNA either with cytotoxic drugs or gene therapy. Little or no interest has been aroused by protein synthesis mechanisms. However, an increasing body of data is emerging about the involvement of translational processes and factors in control of cell proliferation, indicating that protein synthesis can be an additional target for anticancer strategies. In this paper we review the novel insights on the biochemical and molecular events leading to protein biosynthesis and we describe their involvement in cell proliferation and tumorigenesis. A possible mechanistic explanation is given by the interactions that occur between protein synthesis machinery and the proliferative signal transduction pathways and that are therefore suitable targets for indirect modulation of protein synthesis. We briefly describe the molecular tools used to block protein synthesis and the attempts made at increasing their efficacy. Finally, we propose a new multimodal strategy against cancer based on the simultaneous intervention on protein synthesis and signal transduction.
70 citations
TL;DR: Observations from the testing of the induction of apoptosis in B16-F10 melanoma cells provide useful information for the potential clinical application of theophylline as a chemotherapeutic agent against malignant melanoma.
Abstract: Theophylline-treated B16-F10 melanoma cells show a lower experimental metastatic potential in vivo. To identify the possible mechanism(s) involved and on the basis of previous reports, we tested the induction of apoptosis in B16-F10 cells. Fluorescence activated cell sorter (FACS) analysis and p53 overexpression in theophylline-treated B16-F10 melanoma cells appeared to suggest enhanced cell death by apoptosis. The in vivo effects of orally administered theophylline in mice were investigated using different treatment schedules in mice that had undergone hepatic or pulmonary colonization with tumour cells. Mice received theophylline in their drinking water according to different protocols: (i) from 3 days before tumour cell inoculation until animal sacrifice ('early treatment'); (ii) from 3 days before until 3 days after tumour cell inoculation ('short treatment'); or (iii) from 3 days after tumour cell inoculation until animal sacrifice ('late treatment'). In the 'early treatment' group, the number of melanoma foci was reduced by 92.3% in the liver and 81.4% in the lung compared with control animals (P < 0.001). In the 'short treatment' group, there was an 80.2% and 72.2% reduction in liver and lung metastases, respectively (P < 0.001). In the 'late treatment' group, the inhibition of metastasis was 59.7% for liver and 45.3% for lung (P < 0.005). Survival studies showed that 50% of the 'early' theophylline-treated animals died 33.2 +/- 2.0 days after intrasplenic injection (control group: 23.1 1.8 days; P < 0.001) and 33.9 +/- 2.5 days after tail vein injection (control group: 24.1 +/- 1.4 days; P < 0.001). Taken together, these observations provide useful information for the potential clinical application of theophylline as a chemotherapeutic agent against malignant melanoma.
23 citations
TL;DR: Computerised image analysis, performed on histological sections of mouse lungs that had been intravenously injected with B16-F10 melanoma cells was used to develop a novel method to quantify the efficacy of potential antineoplastic drugs, resulting in more accurate data than that obtained from common macroscopical counting of surface metastatic foci.
23 citations