60 research outputs found
Galectin-3C Inhibits Tumor Growth and Increases the Anticancer Activity of Bortezomib in a Murine Model of Human Multiple Myeloma
Galectin-3 is a human lectin involved in many cellular processes including differentiation, apoptosis, angiogenesis, neoplastic transformation, and metastasis. We evaluated galectin-3C, an N-terminally truncated form of galectin-3 that is thought to act as a dominant negative inhibitor, as a potential treatment for multiple myeloma (MM). Galectin-3 was expressed at varying levels by all 9 human MM cell lines tested. In vitro galectin-3C exhibited modest anti-proliferative effects on MM cells and inhibited chemotaxis and invasion of U266 MM cells induced by stromal cell-derived factor (SDF)-1α. Galectin-3C facilitated the anticancer activity of bortezomib, a proteasome inhibitor approved by the FDA for MM treatment. Galectin-3C and bortezomib also synergistically inhibited MM-induced angiogenesis activity in vitro. Delivery of galectin-3C intravenously via an osmotic pump in a subcutaneous U266 cell NOD/SCID mouse model of MM significantly inhibited tumor growth. The average tumor volume of bortezomib-treated animals was 19.6% and of galectin-3C treated animals was 13.5% of the average volume of the untreated controls at day 35. The maximal effect was obtained with the combination of galectin-3C with bortezomib that afforded a reduction of 94% in the mean tumor volume compared to the untreated controls at day 35. In conclusion, this is the first study to show that inhibition of galectin-3 is efficacious in a murine model of human MM. Our results demonstrated that galectin-3C alone was efficacious in a xenograft mouse model of human MM, and that it enhanced the anti-tumor activity of bortezomib in vitro and in vivo. These data provide the rationale for continued testing of galectin-3C towards initiation of clinical trials for treatment of MM
Incorporating novel agents in the treatment of myelodysplastic syndromes
Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal stem cell (SC) disorders that mainly affect the elderly population. They are characterized by ineffective hematopoiesis which results in quantitative and qualitative cellular defects and high incidence of leukemic transformation. Recent advances in MDS research have led to the development of novel agents which appears to improve remission rates and survival when compared to best supportive care. Currently azacitidine, decitabine, and lenalidomide are approved by the US FDA for the treatment of MDS, while the activity of other novel agents such as histone deacetylase inhibitors, farnesyl-transferase inhibitors, novel thrombopoietic agents, and anti-angiogenesis molecules is under evaluation. Erythropoietin-stimulating agents, iron chelating therapy and thrombopoietin receptor ligands may also improve quality of life and possibly prolong survival in MDS patients. The only treatment modality that can achieve long-term survival is the allogeneic SC transplantation which is given only in selected patients. Moreover the heterogeneity of MDS and the patient's advanced age and co-morbidity are significant factors besides cytogenetics, IPSS and WPSS that should be taken into account during the decision-making process. Therefore clinicians should treat patients with MDS on an individual basis aiming the increase of the response rates and the decrease of treatment-associated toxicities. This can only be achieved through the better understanding of the MDS subgroups. If we can better define MDS subgroups we will be able to identify patients who will benefit from the incorporation of the novel agents, as monotherapy or in combinations regimens along with supportive care. © 2009 Elsevier Ltd. All rights reserved
Low dose melphalan is a treatment option in elderly patients with high risk myelodysplastic syndrome or secondary acute myeloblastic leukaemia
We present the case of a 71 year-old man with secondary acute
myeloblastic leukemia, who was successfully treated with low dose
melphalan plus Epo plus G-CSF. We treated the patient with 2 mg of
melphalan once a day orally, G-CSF 5 mg/kg 3 times a week and Epo 10.000
ui subcutaneously 3 times a week until the maximum response was
obtained. Complete remission was achieved after 16 weeks of continuous
treatment. Treatment-related toxicity was not significant. We recommend
the use of low dose melphalan in elderly patients with high risk MDS as
a treatment option
Increased bone mineral density in a subset of patients with relapsed multiple myeloma who received the combination of bortezomib, dexamethasone and zoledronic acid
Effect of pamidronate administration on markers of bone turnover and disease activity in multiple myeloma
Aim: Bisphosphonates are potent inhibitors of osteoclastic activity and
are used in the treatment of multiple myeloma (MM) in combination with
chemotherapy. The effect of pamidronate on markers of bone resorption
[cross-linked N-telopeptides of type I collagen (NTx)] markers of bone
formation [serum alkaline phosphatase (BAP) and osteocalcin (OSC)],
interleukin-6 (IL-6), beta (2)-microglobulin, CRP, paraprotein and
disease-related pain and skeletal events has been evaluated in 62 newly
diagnosed patients with MM. Patients and methods: The patients were
randomly assigned to two groups: the first included 32 patients under
chemotherapy and pamidronate (group I) and the second 30 patients on
chemotherapy only (group II). Pamidronate was administered at a monthly
dose of 90 mg iv, and the above parameters were evaluated at the
beginning of this study and after 1, 3, 6, 9, 12 and 14 months of
treatment. Results: The addition of pamidronate to chemotherapy resulted
in a significant reduction of NTx, IL-6 and paraprotein from the 3rd
month and of beta (2)-microglobulin, CRP and pain from the 6th month of
treatment. No changes of NTx, IL-6, beta2-microglobulin, CRP or skeletal
events were observed in patients of group II, while paraprotein was
significantly reduced after 6 months of treatment. The differences in
NTx, IL-6, paraprotein and beta (2)-microglobulin were statistically
significant between the two groups. Multivariate analysis revealed a
significant correlation between changes of NTx, changes of IL-6 in both
groups and reduction of pain and paraprotein in group I. Conclusions:
These results suggest that pamidronate may have a synergistic action
with chemotherapy in decreasing osteoclastic activity, in reducing
markers of myeloma activity and myeloma related pain and in improving
the quality of life in patients with MM
Increased bone mineral density in a subset of patients with relapsed multiple myeloma who received the combination of bortezomib, dexamethasone and zoledronic acid
Retrospective evaluation of the risk profile in chronic myelogenous leukemia (CML) according to a new prognostic scoring system
Increased bone mineral density in a subset of patients with relapsed multiple myeloma who received the combination of bortezomib, dexamethasone and zoledronic acid
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