Anticancer research
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Anticancer research · May 2003
ReviewT-antigen of human polyomavirus JC cooperates withIGF-IR signaling system in cerebellar tumors of the childhood-medulloblastomas.
Polyomaviruses are implicated in a number of cancers, and the transforming activity of their early protein, large T-antigen, has been documented in a variety of cell types and in experimental animals (1). Although the pathways by which T-antigen induces uncontrolled cell growth are not fully defined, T-antigen mediated inactivation of tumor suppressors, p53 and pRB, is well-documented in some malignancies (2). Here we postulate that functional interaction between the insulin-like growth factor (IGF-IR) and the T-antigen of human polyomavirus JC (JCV T-antigen) may contribute to the process of malignant transformation in medulloblastomas: (i) the IGF-IR signaling system is strongly activated in medulloblastoma cell lines and medulloblastoma biopsies; (ii) the cytoplasmic protein, insulin receptor substrate 1 (IRS-1), is translocated to the nucleus in the presence of JCV T-antigen; (iii) molecular characterization of the interaction between IRS-1 and JCV T-antigen indicates that the binding involves the N-terminal portion of IRS-1 (PH/PTB domain) and the C-terminal region of JCV T-antigen (aa 411-628); and finally (iv) competition for the IRS-1-JCV T-antigen binding attenuates anchorage-independent growth of T-antigen positive medulloblastoma cells in culture. Based on these findings, we propose a novel role for IRS-1 in JCV T-antigen-mediated deregulation of cellular equilibrium, which may involve uncoupling of IRS-1 from the surface receptor and translocation of its function to the nuclear compartment of the cell.
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Anticancer research · May 2002
ReviewMistletoe extracts standardized to mistletoe lectins in oncology: review on current status of preclinical research.
Since the identification and characterization of mistletoe lectins as pharmacologically active constituents at the end of the 1980s, research on mistletoe has made substantial advances. Mistletoe extracts are now available that are standardized in terms of the active mistletoe lectins (measured as mistletoe lectin I, ML I). This constitutes an indispensable precondition for reproducible investigations. ⋯ Cytotoxic effects on tumor cells are likewise apoptosis-related, but at higher levels necrotic cell death predominates. Due to these properties, mistletoe extracts or pure ML I showed antitumoral activities in different animal models. The objective of this review is to present the current state of preclinical research on standardized mistletoe extracts which hence may be included in the category of rationalphytotherapy.
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The majority of patients with advanced ovarian cancer need a second-line treatment for recurrent disease after surgical cytoreduction and first-line chemotherapy. In these patients, treatment planning is mainly dependent on the platinum-free-interval. The patients may be distinguished as platinum-refractory (progression under platinum-based therapy), platinum-resistant (relapse within 6 months), or platinum-sensitive (relapse after 6 months). ⋯ Since response rate and duration to different single-agents are similar, patient convenience, toxicities from prior treatment, side-effects and costs play a role in the drug selection for salvage chemotherapy. Patients with platinum-sensitive disease should receive carboplatin based or carboplatin-plus paclitaxel-based regimens. Secondary surgical cytoreduction may have a role in highly selected patients with good performance status, with long disease-free interval and without extra-abdominal or liver metastases.
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Anticancer research · Nov 2000
ReviewHuman hematopoietic growth factors: old lessons and new perspectives.
Erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage stimulating factor (GM-CSF) are currently licensed for use in cancer patients and play a significant role in the management of anemia and neutropenia following myeloblative chemotherapy. EPO was the first recombinant hematopoietic growth factor to be used clinically after a number of clinical trials which demonstrated its effectiveness in treating mild to moderate cancer-associated anemia with or without concomitant chemotherapy (particulary cisplatin). An extensive research has been made for the improvement of the quality of life with EPO therapy, however, when formally assessed, variable effects of this important treatment have been observed. ⋯ Recently, innovative chimeric growth factor receptor agonists have been synthesized. Synthokine (SC-55494) (a high-affinity human IL-3 receptor ligand analog), myelopoietin (MPO) (activates human IL-3 and G-CSF receptors) and promegapoietin (PMP) (stimulates the human IL-3 and c-mpl receptors) were found to be multilineage hematopoietic growth factors and are currently undergoing clinical trials. Preliminary results suggest that these compounds may have a major impact on the management of myeloablative chemotherapy because of their ability to enhance platelet recovery in addition to their neutrophil restorative activity.
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Anticancer research · Nov 2000
Review Case ReportsMultiple endocrine neoplasia (MEN)--an overview and case report--patient with sporadic bilateral pheochromocytoma, hyperparathyroidism and marfanoid habitus.
The multiple endocrine neoplasia syndromes are divided into two categories: MEN type I and MEN type II. The MEN type II syndrome is further divided into MEN IIa and MEN IIb. The syndromes are characterized by benign and malignant changes in two or more endocrine organs, as well as incidental changes in nervous, muscular and connective tissue. ⋯ We have reported the case of a young man exhibiting bilateral pheochromocytoma. In addition, the patient showed mild primary hyperparathyroidism and marfanoid habitus, all these stigmata usually being part of the MEN-II syndrome. Although this described patient showed a phenotypic mixture of the MEN-IIa and MEN-IIb syndrome, the genetic analysis for MEN II and von-Hippel-Lindau gene did not reveal any pathologic mutations, the endocrine disorders described here are not related to multiple endocrine neoplasia syndromes.