Nestin-Expressing Cells in the Lung: The Bad and the Good Parts

Nestin is a member of the intermediate filament family, which is expressed in a variety of stem or progenitor cells as well as in several types of malignancies. Nestin might be involved in tissue homeostasis or repair, but its expression has also been associated with processes that lead to a poor prognosis in various types of cancer. In this article, we review the literature related to the effect of nestin expression in the lung. According to most of the reports in the literature, nestin expression in lung cancer leads to an aggressive phenotype and resistance to chemotherapy as well as radiation treatments due to the upregulation of phenomena such as cell proliferation, angiogenesis, and metastasis. Furthermore, nestin may be involved in the pathogenesis of some non-cancer-related lung diseases. On the other hand, evidence also indicates that nestin-positive cells may have a role in lung homeostasis and be capable of generating various types of lung tissues. More research is necessary to establish the true value of nestin expression as a prognostic factor and therapeutic target in lung cancer in addition to its usefulness in therapeutic approaches for pulmonary diseases.

Individual and Interactive Temporal Implications of UV-B Radiation and Elevated CO2 on the Morphology of Basil (Ocimum basilicum L.)

Temporal and spatial variations in ozone levels and temporal changes in solar radiation greatly influence ultraviolet radiation incidence to crops throughout their growth, yet the interactive effects of CO2 and UV-B radiation on Basil production under sunlight environmental conditions has not been studied. Basil ‘Genovese’ plants grown under sunlit plant growth chambers were subjected to a combination of supplemental UV-B (0 and 10 kJ m−2d−1) and ambient (420 ppm) and elevated (720 ppm) CO2 treatments for 38 days after 14 days of germination. UV-B radiation treatments caused a decrease in basil stem branching, fresh mass, and stem dry mass under both CO2 treatments when harvested after 17 and 38 days of treatment. There was also an increase in basil leaf surface wax under UV-B (10 kJ m−2d−1) treatment compared to controls (0 kJ m−2d−1). Elevated CO2 treatments caused a decrease in morphological features, including specific leaf area and fresh mass. Interactive effects between UV-B and CO2 treatments existed for some morphological features, including plant height, root surface area, and average root diameter. Understanding the impacts that CO2 and UV-B radiation treatments have on basilcan improve existing varieties for increased tolerance while simultaneously improving yield, plant morphology, and physiology.

EPID-15. AGE AND DOSIMETRIC IMPACTS ON RADIOTHERAPY ASSOCIATED GROWTH IMPAIRMENT FOR PATIENTS WITH INTRACRANIAL GERM CELL TUMORS (GCTs)

PURPOSE Intracranial germ cell tumors (GCTs) are rare pediatric central nervous system (CNS) tumors. Growth impairment induced by radiation treatments was rarely evaluated. We aimed to study the impacts of radiotherapy on height development and identify the dosimetric constraints. MATERIALS AND METHODS A total of 148 pediatric patients diagnosed with GCTs were retrospectively analyzed. Sex, age at irradiation, physical doses and biologically effective dose (BED), height, and endocrine status were obtained from patient records. The cumulative change in height was assessed using age-matched normalized height (ANH). Variables were assessed for correlations and statistical significance. RESULTS Cumulative physical doses and BEDs for the whole brain and pituitary were derived via DVHs and BEDVHs. In contrast to patients >11.5 yr, linear correlations between ANH and cumulative physical doses as well as BEDs to the whole brain and pituitary were identified in patients≤11.5 yr. Dosimetric constrains to the pituitary was 36 Gy for physical dose (AUC=0.70 [95% CI, 0.54-0.86], P< 0.05) and 63 Gy2 BED (AUC=0.69 [95% CI, 0.53-0.86], P< 0.05). Intriguingly, no significant differences in ANH were found among different CSI dose groups in patients ≤11.5 yr. (all P>0.05). Impaired hormone secretions in terms of GH and TSH were identified following cranial irradiation (both P< 0.001), particularly for those with tumors at the suprasellar region (GH: P< 0.01, TSH: P< 0.001). CONCLUSION Our study revealed the impacts of age, dosimetrics and tumor locations for growth impairment. This study will contribute to the optimization of radiation treatment planning and facilitate more individualized therapeutic strategies in pediatric patient with GCTs.

p62/SQSTM1-induced caspase-8 aggresomes are essential for ionizing radiation-mediated apoptosis

The autophagy–lysosome pathway and apoptosis constitute vital determinants of cell fate and engage in a complex interplay in both physiological and pathological conditions. Central to this interplay is the archetypal autophagic cargo adaptor p62/SQSTM1/Sequestosome-1 which mediates both cell survival and endoplasmic reticulum stress-induced apoptosis via aggregation of ubiquitinated caspase-8. Here, we investigated the role of p62-mediated apoptosis in head and neck squamous cell carcinoma (HNSCC), which can be divided into two groups based on human papillomavirus (HPV) infection status. We show that increased autophagic flux and defective apoptosis are associated with radioresistance in HPV(-) HNSCC, whereas HPV(+) HNSCC fail to induce autophagic flux and readily undergo apoptotic cell death upon radiation treatments. The degree of radioresistance and tumor progression of HPV(-) HNSCC respectively correlated with autophagic activity and cytosolic levels of p62. Pharmacological activation of the p62-ZZ domain using small molecule ligands sensitized radioresistant HPV(-) HNSCC cells to ionizing radiation by facilitating p62 self-polymerization and sequestration of cargoes leading to apoptosis. The self-polymerizing activity of p62 was identified as the essential mechanism by which ubiquitinated caspase-8 is sequestered into aggresome-like structures, without which irradiation fails to induce apoptosis in HNSCC. Our results suggest that harnessing p62-dependent sequestration of ubiquitinated caspase-8 provides a novel therapeutic avenue in patients with radioresistant tumors.

Clinical and Preclinical Outcomes of Combining Targeted Therapy With Radiotherapy

In the era of precision medicine, radiation medicine is currently focused on the precise delivery of highly conformal radiation treatments. However, the tremendous developments in targeted therapy are yet to fulfill their full promise and arguably have the potential to dramatically enhance the radiation therapeutic ratio. The increased ability to molecularly profile tumors both at diagnosis and at relapse and the co-incident progress in the field of radiogenomics could potentially pave the way for a more personalized approach to radiation treatment in contrast to the current ‘‘one size fits all’’ paradigm. Few clinical trials to date have shown an improved clinical outcome when combining targeted agents with radiation therapy, however, most have failed to show benefit, which is arguably due to limited preclinical data. Several key molecular pathways could theoretically enhance therapeutic effect of radiation when rationally targeted either by directly enhancing tumor cell kill or indirectly through the abscopal effect of radiation when combined with novel immunotherapies. The timing of combining molecular targeted therapy with radiation is also important to determine and could greatly affect the outcome depending on which pathway is being inhibited.

…and this is my voice: autopathophonography and the politics of variable voice

This essay describes the production and theoretical context of an audio work entitled “…and this is my voice.” In May and June 2010, I took recordings of my voice while on the way into external beam radiation treatments for an aggressive case of papillary thyroid cancer in my neck. I then used these recordings as the raw material for the work. This essay provides full documentation of the production process for those who may want or need something beyond the original audio work to engage with it fully, as well as a theoretical discussion of the ideology of vocal ability: the belief that voices are expressions of subjects’ inner states and abilities. Work available at: https://jonathansterne.bandcamp.com/track/and-this-is-my-voice

Mass Treatment of Flooded Archival Materials by Gamma Radiation

This work describes mass recovery processes of flooded archival materials at industrial scale. The presence of fungi on paper represents a threat to the integrity of the document because they degrade cellulose, one of the main components of paper. Gamma radiation treatments are investigated as mass disinfection agents for their high penetrating power, speed of treatment, and absence of risk due to chemical residuals. We compared two different recovery processes: thermal drying followed by gamma irradiation and gamma irradiation followed by thermal drying. Both these processes were conducted simultaneously on naturally contaminated archival items and on paper specimens artificially contaminated with species test. Efficacy was assessed by culture method and ATP assay, right after the treatments and after four years of storage at room temperature. Coupling gamma irradiation with a drying step with dry heat at 55–60 °C reduces the fungal loads on natural items up to levels close to the detection limits, and the reduction is maintained after four years. On artificial specimens, spore germination is completely inhibited, mycelia growth is also highly affected, but the melanised test species appear to be more resistant. A synergistic effect between gamma irradiation, water content, and thermal drying is highlighted in this paper.

Lipid droplets and ferritin heavy chain: a devilish liaison in human cancer cell radioresistance

Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological signatures of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma and prostate 6 Gy X-ray resistant cancer cells were characterized by an increase of Lipid Droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 overexpression as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect which might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.

The Performance of LiF:Mg-Ti for Proton Dosimetry within the Framework of the MoVe IT Project

Proton therapy represents a technologically advanced method for delivery of radiation treatments to tumors. The determination of the biological effectiveness is one of the objectives of the MoVe IT (Modeling and Verification for Ion Beam Treatment Planning) project of the National Institute for Nuclear Physics (INFN) CSN5. The aim of the present work, which is part of the project, was to evaluate the performance of the thermoluminescent dosimeters (TLDs-100) for dose verification in the proton beam line. Four irradiation experiments were performed in the experimental room at the Trento Proton Therapy Center, where a 150 MeV monoenergetic proton beam is available. A total of 80 TLDs were used. The TLDs were arranged in one or two rows and accommodated in a specially designed water-equivalent phantom. In the experimental setup, the beam enters orthogonally to the dosimeters and is distributed along the proton beam profile, while the irradiation delivers doses of 0.8 Gy or 1.5 Gy in the Bragg peak. For each irradiation stage, the depth–dose curve was determined by the TLD readings. The results showed the good performance of the TLDs-100, proving their reliability for dose recordings in future radiobiological experiments planned within the MoVe IT context.