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Anaplastic thyroid cancer (ATC) is a rare neoplasia with a poor prognosis. Proliferation and apoptosis assays were performed on ATC cell lines (8305C, 8505C) exposed to vinorelbine, lenvatinib, as well as to concomitant combinations. ABCB1, ABCG2 and CSF-1 mRNA expression was evaluated by real time PCR. The relative levels of pospho Akt were investigated as part of a human phospho-kinase array analysis, and CSF-1 and VEGFR-2 protein levels were measured by ELISA. The intracellular concentration of lenvatinib in ATC cells was measured by combined reversed-phase liquid chromatography-tandem mass spectrometry. An ATC subcutaneous xenograft tumor model in nude mice was treated with vinorelbine, lenvatinib, or vinorelbine plus lenvatinib. After treatment with vinorelbine, lenvatinib, a significant antiproliferative effect in ATC cell lines was observed. The concomitant treatment of vinorelbine and lenvatinib revealed synergism for all the fractions of affected cells. A decrease in ABCB1 expression was reported in both ATC cell lines treated with the lenvatinib plus vinorelbine combination, as was an increase in the intracellular concentration of lenvatinib. The combination caused a decrease in Akt, GSK3α/β, PRAS40 and Src phosphorylation, and in both CSF-1 mRNA and protein levels. In the subcutaneous tumor model, the combination reduced the tumor volume during the treatment period. Our results establish the synergistic ATC antitumor activity of a vinorelbine and lenvatinib combination.

Targeting cancer stem cells with oncolytic virus (OV) holds great potential for thorough elimination of cancer cells. Based on our previous studies, we here established 11R-P53 and mGM-CSF carrying oncolytic adenovirus (OAV) SG655-mGMP and investigated its therapeutic effect on hepatocellular carcinoma stem cells Hep3B-C and teratoma stem cells ECCG5. Firstly, the augmenting effect of 11R in our construct was tested and confirmed by examining the expression of EGFP with Fluorescence and FCM assays after transfecting Hep3B-C and ECCG5 cells with OVA SG7605-EGFP and SG7605-11R-EGFP. Secondly, the expressions of 11R-P53 and GM-CSF in Hep3B-C and ECCG5 cells after transfection with OAV SG655-mGMP were detected by Western blot and Elisa assays, respectively. Thirdly, the enhanced growth inhibitory and augmented apoptosis inducing effects of OAV SG655-mGMP on Hep3B-C and ECCG5 cells were tested with FCM assays by comparing with the control, wild type 5 adenovirus, 11R-P53 carrying OVA in vitro. Lastly, the in vivo therapeutic effect of OAV SG655-mGMP toward ECCG5 cell-formed xenografts was studied by measuring tumor volumes post different treatments with PBS, OAV SG655-11R-P53, OAV SG655-mGM-CSF and OAV SG655-mGMP. Treatment with OAV SG655-mGMP induced significant xenograft growth inhibition, inflammation factor AIF1 expression and immune cells infiltration. Therefore, our OAV SG655-mGMP provides a novel platform to arm OVs to target cancer stem cells.

In this note we produce examples of converging sequences of Galois representations, and study some of their properties. Some of the results here are used in the preprint math.NT/0210296.

Motives and automorphic forms of arithmetic type give rise to Galois representations that occur in {\it compatible families}. These compatible families are of p-adic representations with p varying. By reducing such a family mod p one obtains compatible families of mod p representations. While the representations that occur in such a p-adic or mod p family are strongly correlated, in a sense each member of the family reveals a new face of the motive. In recent celebrated work of Wiles playing off a pair of Galois representations in different characteristics has been crucial. In this paper we investigate when a pair of mod p and mod q representations of the absolute Galois group of a number field K simultaneously arises from an {\it automorphic motive}: we do this in the 1-dimensional (Section 2) and 2-dimensional (Section 3: this time assuming $K={\mathbb Q}$) cases. In Section 3 we formulate a mod pq version of Serre's conjecture refining in part a question of Barry Mazur and Ken Ribet., This is an older preprint that was made available elsewhere on Sep. 19, 2001

In 1939, L. Rédei introduced a certain triple symbol in order to generalize the Legendre symbol and Gauss' genus theory. Rédei's triple symbol $[a_1,a_2, p]$ describes the decomposition law of a prime number $p$ in a certain dihedral extension over $\mathbb{Q}$ of degree 8 determined by $a_1$ and $a_2$. In this paper, we show that the triple symbol $[-p_1,p_2, p_3]$ for certain prime numbers $p_1, p_2$ and $p_3$ can be expressed as a Fourier coefficient of a modular form of weight one. For this, we employ Hecke's theory on theta series associated to binary quadratic forms and realize an explicit version of the theorem by Weil-Langlands and Deligne-Serre for Rédei's dihedral extensions. A reciprocity law for the Rédei triple symbols yields certain reciprocal relations among Fourier coefficients.

In this paper we will give a global description of the Frobenius for the division fields of an elliptic curve E which is strictly analogous to the cyclotomic case. This is then applied to determine the splitting of a prime p in subfields of such a division field. Such fields include a large class of non-solvable quintic extensions and our application provides an arithmetic counterpart to Klein's "solution" of quintic equations using elliptic functions. A central role is played by the discriminant of the ring of endomorphisms of the elliptic curve reduced modulo p., Comment: 14 pages

Racemic 6-vinyl-7-oxabicyclo[2.2.1]hept-5-en-2-one, 5-vinyl-7-oxabicyclo[2.2.1]hept-5-en-2-one and their ethylene acetals undergo highly stereoselective Diels-Alder cyclodimerizations. The optically pure semicyclic dienes give the corresponding optically pure dimers with the same ease.