Phase II study of weekly Kahalalide F in patients with advanced malignant melanoma

Martín‐Algarra, Salvador; Espinosa, Enrique; Rubió, J.; López, Juan José; Manzano, José Luís; Alonso-Carrión, Lorenzo; Plazaola, Arrate; Tanovı́c, Adnan; Paz‐Ares, Luis

doi:10.1016/j.ejca.2008.12.005

Cited by 77 publications

(49 citation statements)

References 11 publications

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“…As far as we know, there have been few reports of polysaccharides with structures similar to that of CFPS-1, a protein-bound polysaccharide mainly linked by α-configuration glycosidic bonds with a mean M w of about 283 kDa, inducing both cell growth arrest and apoptosis in human breast tumor (MCF-7 and MDA-MB-231) cells. In the peptide moiety, fifteen amino acids in the CFPS-1 were also detected, and were consistent with a previous study showing that a peptide from Elysia rufescens , a marine gastropod mollusk, significantly in vitro and in vivo suppressed cellular proliferation in human breast tumor cell lines [42]. Therefore, this study provides novel insight into the structural basis of a protein-bound polysaccharide with anticancer effects in vitro and its mechanism.…”

Section: Discussionsupporting

confidence: 90%

Protein-Bound Polysaccharide from Corbicula fluminea Inhibits Cell Growth in MCF-7 and MDA-MB-231 Human Breast Cancer Cells

Liao

Zhong

et al. 2016

PLoS ONE

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A novel protein-bound polysaccharide, CFPS-1, isolated from Corbicula fluminea, is composed predominantly of mannose (Man) and glucose (Glc) in a molar ratio of 3.1:12.7. The polysaccharide, with an average molecular weight of about 283 kDa, also contains 10.8% protein. Atomic force microscopy, high-performance liquid chromatography, Fourier transform infrared spectroscopy, gas chromatography/mass spectrometry, and nuclear magnetic resonance spectroscopy analyses revealed that CFPS-1 has a backbone of 1,6-linked and 1,4,6-linked-α-D-Glc, which is terminated with a 1-linked-α-D-Man residue at the O-4 position of 1,4,6-linked-α-D-Glc, in a molar ratio of 3:1:1. Preliminary in vitro bioactivity tests revealed that CFPS-1 effectively and dose-dependently inhibits human breast cancer MCF-7 and MDA-MB-231 cell growth, with an IC50 of 243 ± 6.79 and 1142 ± 14.84 μg/mL, respectively. In MCF-7, CFPS-1 produced a significant up-regulation of p53, p21, Bax and cleaved caspase-7 and down-regulation of Cdk4, cyclin D1, Bcl-2 and caspase-7. These effects resulted in cell cycle blockade at the S-phase and apoptosis induction. In contrast, in MDA-MB-231, with limited degree of change in cell cycle distribution, CFPS-1 increases the proportion of cells in apoptotic sub-G1 phase executed by down-regulation of Bcl-2 and caspase-7 and up-regulation of Bax and cleaved caspase-7. This study extends our understanding of the anticancer mechanism of C. fluminea protein-bound polysaccharide.

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Section: Discussionsupporting

confidence: 90%

Protein-Bound Polysaccharide from Corbicula fluminea Inhibits Cell Growth in MCF-7 and MDA-MB-231 Human Breast Cancer Cells

Liao

Zhong

et al. 2016

PLoS ONE

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“…Transaminase increases were also reported in phase I trials with the related compound kahalalide F [24][25][26]. An evaluation done with data from the entire clinical development program of elisidepsin, including phase I and II data, showed no serious liver dysfunction as related to elisidepsin; no patients qualified for Hy's law criteria [23].…”

Section: Discussionmentioning

confidence: 95%

First-in-human, phase I study of elisidepsin (PM02734) administered as a 30-min or as a 3-hour intravenous infusion every three weeks in patients with advanced solid tumors

et al. 2015

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This first-in-human, phase I clinical trial was designed to determine the dose-limiting toxicities (DLTs) and the dose for phase II trials (P2D) of elisidepsin (PM02734) administered as a 30-min or as a 3-h intravenous infusion every 3 weeks (q3wk). Between March 2006 and April 2011, 53 patients with advanced malignant solid tumors were enrolled and treated with elisidepsin on the two different q3wk infusion schedules: 22 (30-min) and 31 (3-h), respectively. Doses evaluated ranged from 0.1 to 1.6 mg/m(2) (30-min q3wk) and from 2.0 to 11.0 mg flat dose (FD) (3-h q3wk). In the 30-min q3wk schedule, transient grade 3/4 increases in hepatic transaminases were the DLT, which appeared at the highest doses tested (from 1.1 to 1.6 mg/m(2)). No DLTs were observed on the 3-h schedule at doses up to 11.0 mg q3wk. Common adverse events were grade 1/2 pruritus, nausea, fatigue and hypersensitivity. Of note, myelotoxicity was not observed. Plasma maximum concentration and total drug exposure increased linearly with dose. Prolonged (≥3 months) disease stabilization was observed in pretreated patients with pleural mesothelioma (n = 1) in the 30-min q3wk arm, and with colorectal adenocarcinoma (n = 3), esophagus adenocarcinoma, endometrium adenocarcinoma, pleural mesothelioma, and head and neck carcinoma (n = 1 each) in the 3-h q3wk arm. In conclusion, elisidepsin doses of 1.1 mg/m(2) (equivalent to a FD of 2.0 mg) and 11.0 mg FD are the dose levels achieved for further phase II trials testing the 30-min q3wk and 3-h q3wk schedules, respectively.

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“…These peptides had several effects; they display anti mitotic effect by inhibiting microtubule assembly and polymerization blocking cancer cells in metaphase [17], an antitumor effect by inducing a disturbance in the lysosomal function which leads cell to cell death [18]. They also block the expression of some enzymes involved in DNA replication and cellular proliferation and therefore they inhibit the growth and tumor invasion [19].…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of Two Helix Aspersa Extracts on Tumor Cell Lines (Hut-78 and Seax) Proliferation and MMP-9 Secretion

Romeila

Naïmi²,

Riani

et al. 2016

Int J Pharm Pharm Sci

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Objective: Despite the progress in cancer research, current therapies are ineffective and cause many adverse effects. The discovery of new natural anti-tumor agents that can act on multiple mechanisms of growth and tumor invasion with minor side effects and which can be safe for patients. Therefore, we sought new natural products from an invertebrate organism belonging to the phylum of mollusks: a land snail, Helix aspersa. This study was aimed to evaluate the cytotoxic activity of two extracts prepared from Helix aspersa, on two cutaneous T cell lymphoma cell line (HUT-78 and SeAx). Their effect on MMP-9 expression was also tested. Methods:We prepared from the snail Helix aspersa: an aqueous (AE) and a hydroalcoholic extracts (HAE). We have evaluated the concentration of total proteins and total phenols in these extracts. The percentage of cell mortality was evaluated after incubating the cell lines with the two extracts at different concentrations, by using trypan blue exclusion method. Finally, the tumor cells expression of metalloproteinase MMP-9 was examined by zymography analysis. Results:We have found that 1 mg/ml of AE contains (4.53±0.48 mg) of total proteins and (2.44±0.11 mg) GAE g -1 of phenols. 1 mg/ml of HAE contains (1.83±0.23 mg) of total proteins and (2.81±0.16 mg) GAE g -1 Conclusion: Helix aspersa's extracts had a toxic effect on cutaneous T cell lymphoma (CTCL), but did not inhibit the production of the protease by these two cell lines in culture.of phenols. On one hand, both extracts exerted a toxic effect on these tumor cells. Indeed, aqueous extract induced 44.09 % mortality in HUT-78 and 31.47 % mortality in SeAx tumor cell line with 50 µg/ml. While, the hydroalcoholic extract induced 29.90 % in HUT-78 and 25 % in SeAx. On the other hand, the result showed no changes of MMP-9 expression.

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Phase II study of weekly Kahalalide F in patients with advanced malignant melanoma

Cited by 77 publications

References 11 publications

Protein-Bound Polysaccharide from Corbicula fluminea Inhibits Cell Growth in MCF-7 and MDA-MB-231 Human Breast Cancer Cells

Protein-Bound Polysaccharide from Corbicula fluminea Inhibits Cell Growth in MCF-7 and MDA-MB-231 Human Breast Cancer Cells

First-in-human, phase I study of elisidepsin (PM02734) administered as a 30-min or as a 3-hour intravenous infusion every three weeks in patients with advanced solid tumors

Comparative Study of Two Helix Aspersa Extracts on Tumor Cell Lines (Hut-78 and Seax) Proliferation and MMP-9 Secretion

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