The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models.

BACKGROUND: Lung cancer is the number one cancer killer worldwide. A major drawback in the lung cancer treatment field is the lack of realistic mouse models that replicate the complexity of human malignancy and immune contexture within the tumor microenvironment. Such models are urgently needed. Mutations of the tumor protein p53 are among the most common alterations in human lung cancers. METHODS: Previously, we developed a line of lung cancer mouse model where mutant human TP53-273H is expressed in a lung specific manner in FVB/N background. To investigate whether the human TP53 mutant has a similar oncogenic potential when it is expressed in another strain of mouse, we crossed the FVB/N-SPC-TP53-273H mice to A/J strain and created A/J-SPC-TP53-273H transgenic mice. We then compared lung tumor formation between A/J-SPC-TP53-273H and FVB/N-SPC-TP53-273H. RESULTS: We found the TP53-273H mutant gene has a similar oncogenic potential in lung tumor formation in both mice strains, although A/J strain mice have been found to be a highly susceptible strain in terms of carcinogen-induced lung cancer. Both transgenic lines survived more than 18 months and developed age related lung adenocarcinomas. With micro CT imaging, we found the FVB-SPC-TP53-273H mice survived more than 8 weeks after initial detection of lung cancer, providing a sufficient window for evaluating new anti-cancer agents. CONCLUSIONS: Oncogenic potential of the most common genetic mutation, TP53-273H, in human lung cancer is unique when it is expressed in different strains of mice. Our mouse models are useful tools for testing novel immune checkpoint inhibitors or other therapeutic strategies in the treatment of lung cancer.

Immunopathology of Differing Viral Infection in Allergic Asthma Disease.

The pathophysiology of asthma development is heterogenous. Although complex interactions between factors are present in any one individual, early life viral infections have been shown to play a major role through induction of epithelial damage as well as various innate and adaptive immune responses. The cytokine profile that results from epithelial damage leads to Th2 skewing of the adaptive immune response. Most asthma exacerbations in children and up to half of adults are related to viral infections that also induce epithelial damage and an acute predominately Th2 inflammatory response, leading to acute symptoms and chronic airway remodeling.

1.1 MW peak-power, 7 W average-power, high-spectral-brightness, diffraction-limited pulses from a photonic crystal fiber amplifier.

We report a large-core, Yb-doped photonic crystal fiber amplifier generating diffraction-limited (M2 = 1.04), approximately 0.45 ns, approximately 8 GHz linewidth pulses with energies of 540 microJ, peak power in excess of 1.1 MW, and average power of approximately 7.2 W at a repetition rate of 13.4 kHz. The pulse peak spectral brightness exceeds 10 kW/(sr Hz cm2) and is the highest generated by a fiber source, to our knowledge.

Multistage Yb-doped fiber amplifier generating megawatt peak-power, subnanosecond pulses.

A Q-switched microchip laser generating 1064 nm wavelength, subnanosecond pulses at a 13.4 kHz repetition rate was used to seed a dual-stage amplifier featuring a 40 microm core Yb-doped photonic-crystal fiber (PCF) as the power amplifier. From this source, we obtained diffraction-limited (M2 = 1.05), approximately 450 ps pulses of energy > 0.7 mJ, peak power in excess of 1.5 MW, and an average power of approximately 9.5 W. By further amplifying the PCF output in a multimode 140 microm core Yb-doped fiber, we generated a peak power in excess of 4.5 MW, the highest obtained in a fiber source to our knowledge.