About one half of malignant peripheral nerve sheath tumors (MPNST) have Neurofibromin 1 (NF1) mutations. NF1 is a tumor suppressor gene essential for negative regulation of RAS signaling. Survival for MPNST patients is poor and we sought to identify an effective...
BACKGROUND AND PURPOSE: To evaluate the long-term efficacy of pain reduction by two dose fractionation schedules used for low-dose radiotherapy of painful elbow syndrome. PATIENTS AND METHODS: Between February 2006 and February 2010, 199 evaluable patients were...
This topical review provides an up-to-date overview of the theoretical and practical aspects of therapeutic kilovoltage x-ray beam dosimetry. Kilovoltage x-ray beams have the property that the maximum dose occurs very close to the surface and thus, they are...
BACKGROUND: Although repeat radiation treatment has been shown to palliate pain in patients with bone metastases from multiple primary origin sites, data for the best possible dose fractionation schedules are lacking. We aimed to assess two dose fractionation...
Gold nanoparticles (AuNPs) have generated interest as both imaging and therapeutic agents. AuNPs are attractive for imaging applications since they are nontoxic and provide nearly three times greater X-ray attenuation per unit weight than iodine. As therapeutic agents, AuNPs can sensitize tumor cells to ionizing radiation. To create a nanoplatform that could simultaneously exhibit long circulation times, achieve appreciable tumor accumulation, generate computed tomography (CT) image contrast, and serve as a radiosensitizer, gold-loaded polymeric micelles (GPMs) were prepared. Specifically, 1.9 nm AuNPs were encapsulated within the hydrophobic core of micelles formed with the amphiphilic diblock copolymer poly(ethylene glycol)-b-poly(ε-capralactone). GPMs were produced with low polydispersity and mean hydrodynamic diameters ranging from 25 to 150 nm. Following intravenous injection, GPMs provided blood pool contrast for up to 24 h and improved the delineation of tumor margins via CT. Thus, GPM-enhanced CT imaging was used to guide radiation therapy delivered via a small animal radiation research platform. In combination with the radiosensitizing capabilities of gold, tumor-bearing mice exhibited a 1.7-fold improvement in the median survival time, compared with mice receiving radiation alone. It is envisioned that translation of these capabilities to human cancer patients could guide and enhance the efficacy of radiation therapy.
Al Zaki A, Joh D, Cheng Z, De Barros AL, Kao G, Dorsey J, Tsourkas A.
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Efficient and error-free DNA repair is critical for safeguarding genome integrity, yet it is also linked to radio- and chemoresistance of malignant tumors. miR-34a, a potent tumor suppressor, influences a large set of p53-regulated genes and contributes to p53-mediated apoptosis. However, the effects of miR-34a on the processes of DNA damage and repair are not entirely understood. We explored tet-inducible miR-34a-expressing human p53 wild-type and R273H p53 mutant GBM cell lines, and found that miR-34a influences the broad spectrum of 53BP1-mediated DNA damage response. It escalates both post-irradiation and endogenous DNA damage, abrogates radiation-induced G 2/M arrest and drastically increases the number of irradiated cells undergoing mitotic catastrophe. Furthermore, miR-34a downregulates 53BP1 and inhibits its recruitment to the sites of DNA double-strand breaks. We conclude that whereas miR-34a counteracts DNA repair, it also contributes to the p53-independent elimination of distressed cells, thus preventing the rise of genomic instability in tumor cell populations. These properties of miR-34a can potentially be exploited for DNA damage-effecting therapies of malignancies.
Kofman AV, Kim J, Park SY, Dupart E, Letson C, Bao Y, Ding K, Chen Q, Schiff D, Larner J, Abounader R.
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Dose measurements in pre-clinical and radiobiology studies are frequently inadequate, thus undermining the reliability and reproducibility of the published findings.
Nicole Grosse, Andrea O Fontana, Eugen B. Hug, Antony Lomax, Adolf Coray, Marc Augsburger, Harald Paganetti, Alessandro A Sartori, and Martin Pruschy
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The goal of radiation treatment is to irradiate cancer cells (i.e., a target region) without destroying adjacent healthy tissue. Thus, it is advantageous to form the beam so that it best approximates the target, thereby reducing the amount of dose absorbed in critical regions outside the target area. While multi-leaf collimators are common in human clinical systems, small animal radiotherapy systems are typically limited to a set of fixed-size collimators. For these systems, dose painting can be used for conformal dose delivery, but is significantly slower than a multi-leaf collimator. As a compromise solution, a variable rectangular collimator has been developed for the Small Animal Radiation Research Platform (SARRP). This enables more efficient dose painting via the decomposition of a 2D target region into a minimum number of rectangles of variable size, which is the topic of this paper. The proposed method consists of several distinct steps and was implemented on the SARRP Treatment Planning System (TPS).
Cho N., Wong J., Kazanzides P.
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DTo investigate the impact of the 2 major DNA repair machineries on cellular survival in response to irradiation with the 2 types of ionizing radiation.
Anna Subiel, Giuseppe Schettino et al
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