ABSTRACT
Purpose: The purpose of this study was to analyze the extent of DNA breaks in primary uveal melanoma (UM) with regard to radiotherapy dose delivery (single-dose versus fractionated) and monosomy 3 status. Methods: A total of 54 patients with UM were included. Stereotactic radiotherapy (SRT) was performed in 23 patients, with 8 undergoing single-dose SRT (sdSRT) treatment and 15 receiving fractionated SRT (fSRT). DNA breaks in the enucleated or endoresected tumors were visualized by a TUNEL assay and quantified by measuring the TUNEL-positive area. Protein expression was analyzed by immunohistochemistry. Co-detection of chromosome 3 with proteins was performed by immuno-fluorescent in situ hybridization. Results: The amount of DNA breaks in the total irradiated group was increased by 2.7-fold (P < 0.001) compared to non-irradiated tissue. Tumors treated with fSRT were affected more severely, showing 2.1-fold more DNA damage (P = 0.007) compared to the cases after single (high) dose irradiation (sdSRT). Monosomy 3 tumors showed less DNA breaks compared to disomy 3 samples (P = 0.004). The presence of metastases after radiotherapy correlated with monosomy 3 and less DNA breaks compared to patients with non-metastatic cancer in the combined group with fSRT and sdSRT (P < 0.05). Conclusions: Fractionated irradiation led to more DNA damage than single-dose treatment in primary UM. As tumors with monosomy 3 showed less DNA breaks than those with disomy 3, this may indicate that they are less radiosensitive, which may influence the efficacy of irradiation.
Subject(s)
Chromosomes, Human, Pair 3 , DNA Damage , Melanoma , Uveal Neoplasms , Humans , Uveal Neoplasms/radiotherapy , Uveal Neoplasms/genetics , Melanoma/radiotherapy , Melanoma/genetics , Female , Chromosomes, Human, Pair 3/genetics , Male , Middle Aged , Aged , Adult , Aged, 80 and over , In Situ Hybridization, Fluorescence , In Situ Nick-End Labeling , Radiotherapy Dosage , Immunohistochemistry , Radiosurgery/adverse effects , Radiosurgery/methods , Dose-Response Relationship, RadiationABSTRACT
In this article, two novel distributed variational Bayesian (VB) algorithms for a general class of conjugate-exponential models are proposed over synchronous and asynchronous sensor networks. First, we design a penalty-based distributed VB (PB-DVB) algorithm for synchronous networks, where a penalty function based on the Kullback-Leibler (KL) divergence is introduced to penalize the difference of posterior distributions between nodes. Then, a token-passing-based distributed VB (TPB-DVB) algorithm is developed for asynchronous networks by borrowing the token-passing approach and the stochastic variational inference. Finally, applications of the proposed algorithm on the Gaussian mixture model (GMM) are exhibited. Simulation results show that the PB-DVB algorithm has good performance in the aspects of estimation/inference ability, robustness against initialization, and convergence speed, and the TPB-DVB algorithm is superior to existing token-passing-based distributed clustering algorithms.
