Cytolytic tests with hyperimmune patient sera is a good prognostic tool in racotumomab immunotherapy in advanced non-small cell lung cancer

<p>Aberrant accumulation of a specific sialic acid has been shown to exist in many human malignant cell membranes termed as N-glycolyl neuraminic acid (NeuGc). This particular ganglioside do not normally exist in normal human cells, due to the lack of an enzyme (cytidine monophospho-N-acetyl-neuraminic acid) which is responsible for the synthesis of N—glycolyl neurominic acid. The aberrant expression of NeuGcGM3 ganglioside in the cell surface of certain human tumors, made this molecule an attractive target for immunotherapy. By using 14 F7 monoclonal antibody directed to identify NeuGcGM3 in the tumor tissue, it is possible to select patients for anti-NeuGcGM3 immunotherapy. Racotumomab is an anti-idiotype vaccine, being a mirror image of NeuGcGm3 mimics this ganglioside and triggers an immune response. Antibodies reactive to NeuGcGM3 ganglioside in the vaccinated patient’s sera have cytotoxic anti-tumor properties which can be assessed in L1210 cell line, expressing this ganglioside.</p><p>In this study, we monitored 12 patients with advanced non-small cell lung cancer (NSCLC) who are on racotumomab vaccine maintenance following chemotherapy. Cytotoxic tests with vaccinated patients’ sera were performed using L1210 cell lines at the 3^rd, 6^th, 9^th, and 12^th months of vaccination and the results were compared with clinical outcomes. Serum antibodies to NeuGcGm3 ganglioside were also checked before initiation and thereafter with the same intervals. The aim of the study was to investigate the value of antibodies and cytotoxic test as biomarkers for treatment outcome. Our observation confirmed that consistently higher cytotoxicity rates in the cell culture correlated with better progression free survivals of the patients who are on racotumomab maintenance.</p>

Lectin detection of cell surface saccharides remodeling induced by development of P-glycoprotein mediated multidrug resistance phenotype in L1210 leukemia cells

P-glycoprotein is an ATP dependent drug efflux pump the expression of which is responsible for strong depression of cell sensitivities to large group of structurally unrelated substances in neoplastic cells. We found that the expression of this protein in mice leukemia cells L1210 is associated with massive remodeling of cell surface saccharides. This remodeling is consistent with the alteration of cellular contents of UDP-sugars, glycogen and glycoproteins when P-gp positive and P-gp negative L1210 cell variants were compared. The current paper is focused on bringing the state of art information about this topic.

BENZOPHENONE GLUCOSIDE ISOLATED FROM THE ETHYL ACETATE EXTRACT OF THE BARK OF MAHKOTA DEWA [Phaleria macrocarpa (Scheff.) Boerl.] AND ITS INHIBITORY ACTIVITY ON LEUKEMIA L1210 CELL LINE

Isolation and elucidation of benzophenone glucoside from ethyl acetate extract of Phaleria macrocarpa bark and its inhibitory activity test against leukemia L1210 cell line have been done. The Phaleria macrocarpa bark were macerated using n-hexane, ethyl acetate, and ethanol, respectively. The ethyl acetate extract was then chromatographed on silica gel column and gradiently eluted by n-hexane - ethyl acetate - ethanol with the composition from 20:1:0 until 0:0:1, gave eight fractions. Separation of fraction 6 using semipreparative HPLC on reverse phase column (Capcell Pak C-18 SG120, 15 mm I.D. x 250 mm) using methanol - water (40:60, 5 mL/min) gave a brown powder, with the melting point of 182.3 ºC. Spectroscopic analysis and comparison of its physico-chemical data, this compound was clarified as 2,4'-dihydroxy-4-methoxy-benzophenone-6-O-b-D-glucopyranoside (3). Inhibitory activity of its compound against leukemia L1210 cell line showed that this compound exhibited inhibitory activity with IC50 was 5.1mg/mL. Keywords: Phaleria macrocarpa, 2,4'-dihydroxy-4-methoxybenzophenone-6-O-b-D-glucopyranoside, cytotoxic activity, leukemia L1210

Alkaloids from Lindera Aggregata

Eight alkaloids, including a new compound, (+)-norboldine acetate (1), and seven known ones, (+)-norboldine (2), (+)-boldine (3), (+)-laurotetanine (4), (+)- N-methyllaurotetanine (5), (+)-reticuline (6), (–)-pronuciferine (7), and pallidine (8) were isolated from the roots of Lindera aggregata. The structures of these alkaloids were determined by spectroscopic and chemical methods, especially 2D NMR techniques, which also allowed the first full NMR assignments of alkaloids 2, 4 and 5. Among them, the 1D NMR chemical shifts of (+)-norboldine (2) showed a remarkable environmental sensitive behavior. All the alkaloids were tested in cytotoxicity assays against L1210 and K562 tumor cell lines; only (+)-norboldine (2) showed weak activity against the L1210 cell line.