Effect of Radiation Dose Fractionation and Radiation Energy on Gold Nanoparticle Enhancement of Radiation Therapy

Objective: Gold nanoparticles (GNPs) have the potential to enhance the effects of radiation therapy, using Auger electrons to cause additional damage to tumors. In this work, we explore the effect of two clinically important variables: dose fractionation and radiation energy. In clinical radiation therapy, radiation is fractionated (split into multiple sessions) and high-energy radiation is used. However, in the field of GNP research, radiation has generally been given in one session and lower radiation energies have generally been used. Methods: Mice with JC breast tumors implanted in the flank were given radiation therapy over 1, 2, or 4 fractions, with radiation energies of either 250 kilovolts peak or 350 kilovolts peak. A survival analysis and a weighted generalized estimating equation analysis were used to. Results: The use of multiple radiation fractions (between 1 and 4) and the use of radiation doses between 250-350 kVp were only different by statistically insignificant amounts, after the contributions from time, sex, age at irradiation and original tumor volume were accounted for. A survival analysis found a higher likelihood of death for female mice, mice given 350 kilovolts peak radiation (versus 250 kilovolts peak), and mice with larger tumors, as well as a lower likelihood of death for mice irradiated at an older age; fractionated radiation did not have a statistically significant effect. Conclusion: These results suggest that GNPs have the potential to enhance radiation therapy when used with fractionated radiation

Marker Assisted Screening of Nepalese rice for bacterial leaf blight (BLB) resistance

Bacterial Leaf Blight (BLB) is the most important yield limiting factor in Nepalese rice. BLB resistance rice varieties are highly demanding in the country. Breeding efforts for developing disease resistant depends on availability and use of resistant gene donors. Nepalese rice landraces could be the source of resistant gene. Therefore, ninety six Nepalese rice accessions were screened using eight Simple Sequence Repeats (SSR) markers and one Sequence Tagged Sites (STS) marker for presence and absence of BLB resistance gene. We have detected BLB resistance gene Xa-10 on five accessions, Xa-13 on six accessions, Xa-7 on 23 accessions, Xa-3 and Xa-4 on 52 accessions, Xa-5 on 25 accessions, Xa-8 on 30 rice accessions. No any rice accessions tested have Xa-21. Similarly, 17 rice accessions showed three and more than three BLB resistance genes. Presence of Xa-13 on susceptible check variety CNTRL-85033 confirmed that this resistant gene is not working in Nepalese rice field. Therefore, Nepal need to pyramide the BLB resistant genes for durable resistance.Nepal Journal of Biotechnology. Dec. 2015 Vol. 3, No. 1: 35-3

Effects of Nanoparticle Size and Radiation Energy on Copper-Cysteamine Nanoparticles for X-ray Induced Photodynamic Therapy

The Copper-cysteamine (Cu-Cy) nanoparticle is a novel sensitizer with a potential to increase the effectiveness of radiation therapy for cancer treatment. In this work, the effect of nanoparticle size and the energy of X-rays on the effectiveness of radiation therapy are investigated. The effect of the particle size on their performance is very complicated. The nanoparticles with an average size of 300 nm have the most intense photoluminescence, the nanoparticles with the average size of 100 nm have the most reactive oxygen species production upon X-ray irradiation, while the nanoparticles with the average size of 40 nm have the best outcome in the tumor suppression in mice upon X-ray irradiation. For energy, 90 kVp radiation resulted in smaller tumor sizes than 250 kVp or 350 kVp radiation energies. Overall, knowledge of the effect of nanoparticle size and radiation energy on radiation therapy outcomes could be useful for future applications of Cu-Cy nanoparticles

Effects of Nanoparticle Size and Radiation Energy on Copper-Cysteamine Nanoparticles for X-ray Induced Photodynamic Therapy

The Copper-cysteamine (Cu-Cy) nanoparticle is a novel sensitizer with a potential to increase the effectiveness of radiation therapy for cancer treatment. In this work, the effect of nanoparticle size and the energy of X-rays on the effectiveness of radiation therapy are investigated. The effect of the particle size on their performance is very complicated. The nanoparticles with an average size of 300 nm have the most intense photoluminescence, the nanoparticles with the average size of 100 nm have the most reactive oxygen species production upon X-ray irradiation, while the nanoparticles with the average size of 40 nm have the best outcome in the tumor suppression in mice upon X-ray irradiation. For energy, 90 kVp radiation resulted in smaller tumor sizes than 250 kVp or 350 kVp radiation energies. Overall, knowledge of the effect of nanoparticle size and radiation energy on radiation therapy outcomes could be useful for future applications of Cu-Cy nanoparticles

Dispersion of the resonant second order nonlinearity in 2D semiconductors probed by femtosecond continuum pulses

We demonstrate an effective microspectroscopy technique by tracing the dispersion of second order nonlinear susceptibility (χ(2)) in a monolayer tungsten diselenide (WSe2). The χ(2) dispersion obtained with better than 3 meV photon energy resolution showed peak value being within 6.3-8.4×10-19 m2/V range. We estimate the fundamental bandgap to be at 2.2 eV. Sub-structure in the χ(2) dispersion reveals a contribution to the nonlinearity due to exciton transitions with exciton binding energy estimated to be at 0.7 eV

Gold nanoparticles enhance radiation therapy at low concentrations, and remain in tumors for days

Gold nanoparticles are a potential method for enhancing radiation therapy, causing extra damage to tumors when irradiated through the Auger effect. One of the major obstacles to using gold nanoparticles in human trials is the relatively large amount of gold required. This paper details an experiment where a relatively small amount of gold (200 g) was used to significantly reduce tumor volume in mice, as well as the results of an inter-tissue biodistribution experiment. Using a longitudinal analysis, tumor size as a function of time was found to be significantly reduced when mice were given 200 g of gold nanoparticles and 20 Gray of radiation, compared to radiation alone. 200 g in a 20-gram mouse would be mass equivalent to 750 mg of gold in a 75 kg person. Biodistribution measurements demonstrated that gold nanoparticles stayed in the tumor for at least one week after injection when targeted to tumors using pH-Low Insertion Peptide and intratumoral injections. These results show gold nanoparticles to be effective at one of the smallest amounts of gold ever attempted in a mouse, and showed that tumor targeting has the potential to keep gold nanoparticles available in tumors long enough to be beneficial to fractionated radiation treatments (a key component of radiation therapy in the clinic)

X-ray induced photodynamic therapy with copper-cysteamine nanoparticles in mice tumors

Photodynamic therapy (PDT), a treatment that uses a photosensitizer, molecular oxygen, and light to kill target cells, is a promising cancer treatment method. However, a limitation of PDT is its dependence on light that is not highly penetrating, precluding the treatment of tumors located deep in the body. Copper-cysteamine nanoparticles are a new type of photosensitizer that can generate cytotoxic singlet oxygen molecules upon activation by X-rays. In this paper, we report on the use of copper-cysteamine nanoparticles, designed to be targeted to tumors, for X-ray–induced PDT. In an in vivo study, results show a statistically significant reduction in tumor size under X-ray activation of pH-low insertion peptide–conjugated, copper-cysteamine nanoparticles in mouse tumors. This work confirms the effectiveness of copper-cysteamine nanoparticles as a photosensitizer when activated by radiation and suggests that these Cu-Cy nanoparticles may be good candidates for PDT in deeply seated tumors when combined with X-rays and conjugated to a tumor-targeting molecule

The Histone Demethylase HR Suppresses Breast Cancer Development through Enhanced CELF2 Tumor Suppressor Activity

The hairless (HR) gene encodes a transcription factor with histone demethylase activity that is essential for development and tissue homeostasis. Previous studies suggest that mutational inactivation of HR promotes tumorigenesis. To investigate HR mutations in breast cancer, we performed targeted next-generation sequencing using DNA isolated from primary breast cancer tissues. We identified HR somatic mutations in approximately 15% of the patient cohort (n = 85), compared with 23% for BRCA2, 13% for GATA3, 7% for BRCA1, and 3% for PTEN in the same patient cohort. We also found an average 23% HR copy number loss in breast cancers. In support of HR’s antitumor functions, HR reconstitution in HR-deficient human breast cancer cells significantly suppressed tumor growth in orthotopic xenograft mouse models. We further demonstrated that HR’s antitumor activity was at least partly mediated by transcriptional activation of CELF2, a tumor suppressor with RNA-binding activity. Consistent with HR’s histone demethylase activity, pharmacologic inhibition of histone methylation suppressed HR-deficient breast cancer cell proliferation, migration and tumor growth. Taken together, we identified HR as a novel tumor suppressor that is frequently mutated in breast cancer. We also showed that pharmacologic inhibition of histone methylation is effective in suppressing HR-deficient breast tumor growth and progression