Expression and autoregulation of transforming growth factor beta receptor mRNA in small-cell lung cancer cell lines.

In small-cell lung cancer cell lines resistance to growth inhibition by transforming growth factor (TGF)-beta 1, was previously shown to correlate with lack of TGF-beta receptor I (RI) and II (RII) proteins. To further investigate the role of these receptors, the expression of mRNA for RI, RII and beta-glycan (RIII) was examined. The results showed that loss of RII mRNA correlated with TGF-beta 1 resistance. In contrast, RI-and beta-glycan mRNA was expressed by all cell lines, including those lacking expression of these proteins. According to Southern blot analysis, the loss of type II mRNA was not due to gross structural changes in the gene. The effect of TGF-beta 1 on expression of TGF-beta receptor mRNA (receptor autoregulation) was examined by quantitative Northern blotting in four cell lines with different expression of TGF-beta receptor proteins. In two cell lines expressing all three TGF-beta receptor proteins beta-glycan mRNA was rapidly down-regulated and this effect was sustained throughout the 24 h observation period. RI and RII mRNAs were slightly increased 24 h after treatment. In one cell line sensitive to growth inhibition by TGF-beta, 1 but lacking beta-glycan expression, and one cell line expressing only beta-glycan and thus TGF-beta 1 -resistant, no autoregulation of mRNA of either TGF-beta receptor was demonstrated. The results suggest that TGF-beta 1 regulates the expression of its receptors, in particular beta-glycan, and that this effect is dependent on co-expression of beta-glycan, RI and RII

Reconstruction of implanted marker trajectories from cone-beam CT projection images using interdimensional correlation modeling

PURPOSE: Cone-beam CT (CBCT) is a widely used imaging modality for image-guided radiotherapy. Most vendors provide CBCT systems that are mounted on a linac gantry. Thus, CBCT can be used to estimate the actual 3-dimensional (3D) position of moving respiratory targets in the thoracic/abdominal region using 2D projection images. The authors have developed a method for estimating the 3D trajectory of respiratory-induced target motion from CBCT projection images using interdimensional correlation modeling. METHODS: Because the superior-inferior (SI) motion of a target can be easily analyzed on projection images of a gantry-mounted CBCT system, the authors investigated the interdimensional correlation of the SI motion with left-right and anterior-posterior (AP) movements while the gantry is rotating. A simple linear model and a state-augmented model were implemented and applied to the interdimensional correlation analysis, and their performance was compared. The parameters of the interdimensional correlation models were determined by least-square estimation of the 2D error between the actual and estimated projected target position. The method was validated using 160 3D tumor trajectories from 46 thoracic/abdominal cancer patients obtained during CyberKnife treatment. The authors' simulations assumed two application scenarios: (1) retrospective estimation for the purpose of moving tumor setup used just after volumetric matching with CBCT; and (2) on-the-fly estimation for the purpose of real-time target position estimation during gating or tracking delivery, either for full-rotation volumetric-modulated arc therapy (VMAT) in 60 s or a stationary six-field intensity-modulated radiation therapy (IMRT) with a beam delivery time of 20 s. RESULTS: For the retrospective CBCT simulations, the mean 3D root-mean-square error (RMSE) for all 4893 trajectory segments was 0.41 mm (simple linear model) and 0.35 mm (state-augmented model). In the on-the-fly simulations, prior projections over more than 60° appear to be necessary for reliable estimations. The mean 3D RMSE during beam delivery after the simple linear model had established with a prior 90° projection data was 0.42 mm for VMAT and 0.45 mm for IMRT. CONCLUSIONS: The proposed method does not require any internal/external correlation or statistical modeling to estimate the target trajectory and can be used for both retrospective image-guided radiotherapy with CBCT projection images and real-time target position monitoring for respiratory gating or tracking.NHMRC, National Research Foundation of Kore

Infinite qubit rings with maximal nearest neighbor entanglement: the Bethe ansatz solution

We search for translationally invariant states of qubits on a ring that maximize the nearest neighbor entanglement. This problem was initially studied by O'Connor and Wootters [Phys. Rev. A {\bf 63}, 052302 (2001)]. We first map the problem to the search for the ground state of a spin 1/2 Heisenberg XXZ model. Using the exact Bethe ansatz solution in the limit of an infinite ring, we prove the correctness of the assumption of O'Connor and Wootters that the state of maximal entanglement does not have any pair of neighboring spins ``down'' (or, alternatively spins ``up''). For sufficiently small fixed magnetization, however, the assumption does not hold: we identify the region of magnetizations for which the states that maximize the nearest neighbor entanglement necessarily contain pairs of neighboring spins ``down''.Comment: 10 pages, 4 figures; Eq. (45) and Fig. 3 corrected, no qualitative change in conclusion

Growth suppression by transforming growth factor beta 1 of human small-cell lung cancer cell lines is associated with expression of the type II receptor.

Nine human small-cell lung cancer cell lines were treated with transforming growth factor beta 1 (TGF-beta 1). Seven of the cell lines expressed receptors for transforming growth factor beta (TGF-beta-r) in different combinations between the three human subtypes I, II and III, and two were receptor negative. Growth suppression was induced by TGF-beta 1 exclusively in the five cell lines expressing the type II receptor. For the first time growth suppression by TGF-beta 1 of a cell line expressing the type II receptor without coexpression of the type I receptor is reported. No effect on growth was observed in two cell lines expressing only type III receptor and in TGF-beta-r negative cell lines. In two cell lines expressing all three receptor types, growth suppression was accompanied by morphological changes. To evaluate the possible involvement of the retinoblastoma protein (pRb) in mediating the growth-suppressive effect of TGF-beta 1, the expression of functional pRb, as characterised by nuclear localisation, was examined by immunocytochemistry. Nuclear association of pRb was only seen in two of the five TGF-beta 1-responsive cell lines. These results indicate that in SCLC pRb is not required for mediation of TGF-beta 1-induced growth suppression