A coupled column generation,mixed integer approach to optimal planning of intensity modulated radiation therapy for cancer

Approximately 40% of all U.S. cancer cases are treated with radiation therapy. In Intensity-Modulated Radiation Therapy (IMRT) the treatment planning problem is to choose external beam angles and their corresponding intensity maps (showing how the intensity varies across a given beam) to maximize tumor dose subject to the tolerances of surrounding healthy tissues. Dose, like temperature, is a quantity defined at each point in the body, and the distribution of dose is determined by the choice of treatment parameters available to the planner. In addition to absolute dose limits in healthy tissues, some tissues have at least one dose-volume restriction that requires a fraction of its volume to not exceed a specified tighter threshold level for damage. There may also be a homogeneity limit for the tumor that restricts the allowed spread of dose across its volume. We formulate this planning problem as a mixed integer program over a coupled pair of column generation processes -- one designed to produce intensity maps, and a second specifying protected area choices for tissues under dose-volume restrictions. The combined procedure is shown to strike a balance between computing an approximately optimal solution and bounding its maximum possible suboptimality that we believe holds promise for implementations able to offer the power and flexibility of mixed-integer linear programming models on instances of practical scale.A portion of the work of Dr. Langer, Mr. Thai and Dr. Preciado-Walters was supported by National Science Foundation grant ECS-0120145 and National Cancer Institute 1R41CA91688-01. Dr. Rardin is participated while on rotation as Program Director for Operations Research and Service Enterprise Engineering at the National Science Foundation.     

9,12-Dibenzothiazolylhypericin and 10,11-Dibenzothiazolyl-10,11-didemethylhypericin: Photochemical Properties of Hypericin Derivatives Depending on the Substitution Site

Summary. Investigating the properties of similar but regioselectively differently substituted hypericin derivatives, 9,12-dibenzothiazolylhypericin was synthesized and compared with the recently prepared 10,11-analogue. A significant difference in the ability to generate singlet oxygen and/or reactive oxygen species and different absorption spectra of these two derivatives were observed.     

手性纳米材料: 生物成像、 生物传感与治疗

手性无机纳米结构不仅形貌和结构可调控、 易于表面功能化修饰, 而且光学性质独特, 在生物领域的应用上展现了很大的优异性. 本文综述了近年来手性纳米技术在生物医学领域的研究进展, 重点介绍了手性金属和手性半导体纳米结构的合成策略、 圆二色效应、 光手性机制及在生物成像、 生物传感、 肿瘤以及神经退行性疾病等医学领域的应用. 手性纳米材料的研究丰富了生物化学的纳米技术手段, 促进了肿瘤等重大疾病诊断与治疗技术的进步, 推动了手性在生命科学中的发展, 鼓励了研究者对这一新兴领域的持续探索与挑战.     

Documentation of progress in voice therapy: perceptual, acoustic, and laryngostroboscopic findings pretherapy and posttherapy

The effect of voice therapy in a group of chronically dysphonic patients with diverse diagnoses was studied according to the normal clinical procedure. The results were evaluated by perceptual rating, acoustic analysis, and the assessment of laryngostroboscopic recordings. Although the group effects for the differences between posttherapy and pretherapy data were clearly significant, the effects of voice therapy for the individual patients were divergent. For each of the three evaluation methods, a significant improvement was found for about 40% to 50% of the patients. The diversity of the therapy outcome among the patients could not be explained by the pretherapy status nor by age, gender, or diagnosis groups. In general, the perceptual ratings and the acoustic parameters from the baseline data were clearly correlated. However, these characterizations of the voice were only moderately correlated with the visual evaluation of the vocal fold vibrations. Relations among the three evaluation tools for the changes caused by voice therapy were very weak. The low correlation among the three methods suggests that a multidimensional evaluation of the voice is necessary to give a complete picture of the therapy outcome.     

Combined imaging biomarkers for therapy evaluation in glioblastoma multiforme: correlating sodium MRI and F-18 FLT PET on a voxel-wise basis

We evaluate novel magnetic resonance imaging (MRI) and positron emission tomography (PET) quantitative imaging biomarkers and associated multimodality, serial-time-point analysis methodologies, with the ultimate aim of providing clinically feasible, predictive measures for early assessment of response to cancer therapy. A focus of this work is method development and an investigation of the relationship between the information content of the two modalities. Imaging studies were conducted on subjects who were enrolled in glioblastoma multiforme (GBM) therapeutic clinical trials. Data were acquired, analyzed and displayed using methods that could be adapted for clinical use. Subjects underwent dynamic [¹⁸F]fluorothymidine (F-18 FLT) PET, sodium (²³Na) MRI and 3-T structural MRI scans at baseline (before initiation of therapy), at an early time point after beginning therapy and at a late follow-up time point after therapy. Sodium MRI and F-18 FLT PET images were registered to the structural MRI. F-18 FLT PET tracer distribution volumes and sodium MRI concentrations were calculated on a voxel-wise basis to address the heterogeneity of tumor physiology. Changes in, and differences between, these quantities as a function of scan timing were tracked.     

Spiro-Azoles Thiazolidinone in the Synthesis of Polymethine Cyanine Dyes

A series of some spiro azoles (pyrazolone, oxazolone, and/or imidazolone) inconjucton with heterocyclic thiazolidinone derivatives were prepared as starting materials in the synthesis of polymethine cyanine dyes. Reaction of spiro 2-formyl (oxime) azoles thiazolidinone derivatives with equi- and/or molar ratios of 2(4)-methyl substituted heterocyclic quaternary salts afforded the corresponding compound pentamethine, aza-mero cyanine, and azapentamethine cyanine dyes respectively. Elemental analyses, IR, 1 H-NMR, and mass-spectra identified the new spiro heterocyclic compounds and polymethine cyanine dyes. The visible absorption spectra of all new polymethine cyanine dyes were investigated.     

A Photoisomerizable Zinc (II) Complex Inhibits Microtubule Polymerization for Photoactive Therapy

The photoisomerization-induced cytotoxicity in photopharmacology provides a unique pathway for phototherapy because it is independent of endogenous oxygen. In this study, we developed a biosafe photoisomerizable zinc(II) complex ( Zn1 ), which releases its trans ligand ( trans -L1 ) after being irradiated with blue light. This causes the complex to undergo photoisomerization and produce the toxic cis product ( cis -L1 ) and generate singlet oxygen (¹O₂). The resulting series of events caused impressive phototoxicity in hypoxic A431 skin cancer cells, as well as in a tumor model in vivo. Interestingly, Zn1 was able to inhibit tumor microtubule polymerization, while still showing good biocompatibility and biosafety in vivo. This photoisomerizable zinc(II) complex provides a novel strategy for addressing the oxygen-dependent limitation of traditional photodynamic therapy.     

Smart Nanosensitizers for Activatable Sono-Photodynamic Immunotherapy of Tumors by Redox-Controlled Disassembly

Tumor-targeted and stimuli-activatable nanosensitizers are highly desirable for cancer theranostics. However, designing smart nanosensitizers with multiple imaging signals and synergistic therapeutic activities switched on is challenging. Herein, we report tumor-targeted and redox-activatable nanosensitizers ( 1-NPs ) for sono-photodynamic immunotherapy of tumors by molecular co-assembly and redox-controlled disassembly. 1-NPs show a high longitudinal relaxivity (r₁=18.7±0.3 mM⁻¹ s⁻¹), but “off” dual fluorescence (FL) emission (at 547 and 672 nm), “off” sono-photodynamic therapy and indoleamine 2,3-dioxygenase 1 (IDO1) inhibition activities. Upon reduction by glutathione (GSH), 1-NPs rapidly disassemble and remotely release small molecules 2-Gd , Zn-PPA-SH and NLG919, concurrently switching on (1) dual FL emission, (2) sono-photodynamic therapy and (3) IDO1 inhibition activities. After systemic injection, 1-NPs are effective for bimodal FL and magnetic resonance (MR) imaging-guided sono-photodynamic immunotherapy of orthotropic breast and brain tumors in mice under combined ultrasound (US) and 671-nm laser irradiation.