Growth hormone-releasing hormone (GHRH) antagonists exert antitumor functions in different experimental cancers. However, their role in combination with radiotherapy in non-small cell lung cancer (NSCLC) remains unknown. Therefore, we investigated the radiosensitizing effect of GHRH antagonists in NSCLC. A549 and H522 NSCLC cell lines were exposed to ionizing radiation (IR) and GHRH antagonists MIA-602 and MIA-690, either individually or in combination. Cell viability and proliferation were evaluated by MTT, BrdU, flow cytofluorimetry, and clonogenic assays; gene and protein expression, signaling pathways, and apoptosis were analyzed by real-time PCR, Western blot, annexin staining, and caspase-3 assay. GHRH antagonists showed antitumor effects alone and potentiated IR-induced inhibition of cell viability and proliferation. The combination of MIA-690 and IR decreased the expression of GHRH receptor, its oncogenic splice variant 1, and IGF1 mRNA levels. Additionally, cell cycle inhibitors and proapoptotic markers were upregulated, whereas cyclins, oncogenic MYC, and the antiapoptotic protein Bcl-2 were downregulated. Radioresistance was prevented by MIA-690, which also blunted epithelial–mesenchymal transition by enhancing E-cadherin and reducing mesenchymal, oxidative, and proangiogenic effectors. Finally, both MIA-602 and MIA-690 enhanced radiosensitivity in primary human NSCLC cells. These findings highlight the potential of GHRH antagonists as radiosensitizers in NSCLC treatment.

• Book : 26(7)
• Pub. Date : 2025
• Page : pp.3267-3267
• Keyword :

AbstractThe increasing threat of heat stress poses significant risks to human health globally. To quantify heat exposure more effectively, integrated heat stress indicators (HSIs) have been developed to simplify the classification of heat stress severity and assist in public heat warnings. However, their ability to accurately predict daily heat stroke cases has not been fully assessed. In this study, we evaluated the performance of multiple HSIs in forecasting the number of heat stroke‐related emergency ambulance dispatches (HT‐EADs) across 47 prefectures in Japan and compared their accuracy to models using raw meteorological variables. Our results indicate that, while HSIs simplify the process of assessing heat stress, they generally show lower performances than models based on raw meteorological data. Among the eight HSIs tested, the Wet Bulb Globe Temperature (TWBG) showed the strongest predictive power, with median R2 values of 0.77 and 0.70 for the calibration and validation periods, respectively. However, models incorporating air temperature, relative humidity, wind speed, and solar radiation outperformed TWBG, achieving R2 values of 0.85 and 0.74. We also observed spatial variability in HSI performance, particularly in cooler regions like Hokkaido, where HSIs provided no improvement over temperature alone. Given these findings, we recommend that HSIs be rigorously evaluated with local health data before being used in heat warning systems for specific locations. For predictions requiring high accuracy, raw meteorological variables could be prioritized to ensure greater precision.

• Book : 9(4)
• Pub. Date : 2025
• Page :
• Keyword :

Background: Recurrent oral squamous cell carcinoma (re-OSCC) poses a serious therapeutic challenge and is linked to poor survival outcomes. SOX2 and NANOG, key transcription factors in cancer stem cell biology, may drive tumor progression and therapy resistance. However, their prognostic value in re-OSCC and their relationship to adjuvant therapy remain unclear. Methods: We retrospectively analyzed a single-center cohort of 94 patients with re-OSCC treated with curative intent via (1) surgery alone, (2) surgery plus adjuvant radiotherapy (RT), or (3) surgery plus adjuvant radiochemotherapy (RCT). Tissue microarrays (TMAs) were constructed from matched primary and recurrent tumors and immunohistochemical (IHC) staining for SOX2, and NANOG was quantified using H-scores. Post-recurrence overall survival (prOS) and post-recurrence disease-free survival (prDFS) were evaluated using Kaplan–Meier analysis and Cox proportional hazards models. Results: SOX2 expression and survival: Elevated SOX2 expression (H-score > 14) in re-OSCC was significantly associated with improved prOS (p = 0.013) and prDFS (p = 0.026). Notably, patients who had received adjuvant therapy (particularly RCT) showed higher SOX2 levels in recurrent tumors compared to those treated with surgery alone. NANOG expression and therapy: NANOG expression declined markedly from primary to recurrent tumors (median H-score 42.2 vs. 8.7; p < 0.001). This decline was most pronounced in patients treated with surgery alone. Despite this dynamic change, NANOG expression did not correlate significantly with prOS or prDFS. Other prognostic factors include advanced tumor stage (rT2–rT4) and lymph node involvement (rN+/x)m which remained significant predictors of worse survival in the recurrent setting, regardless of adjuvant therapy. Conclusion: SOX2 overexpression in re-OSCC correlates with better survival, suggesting a unique prognostic role distinct from primary disease. Adjuvant therapy, especially RCT, appears to maintain or elevate SOX2 levels, potentially contributing to improved treatment response. In contrast, although NANOG expression decreases in recurrence, particularly in patients who undergo surgery alone, it does not significantly affect survival outcomes. These findings underscore the importance of context-specific biomarker assessments and provide a rationale for incorporating SOX2 status into personalized treatment strategies for re-OSCC.

• Book : 17(7)
• Pub. Date : 2025
• Page : pp.1181-1181
• Keyword :

Cardiotoxicity represents a critical challenge in cancer therapy, particularly in the treatment of thoracic tumors, such as lung cancer and lymphomas, as well as breast cancer. These malignancies stand out for their high prevalence and the widespread use of cardiotoxic treatments, such as chemotherapy, radiotherapy, and immunotherapy. This work underscores the importance of preclinical models in uncovering the mechanisms of cardiotoxicity and developing targeted prevention and mitigation strategies. In vitro models provide valuable insights into cellular processes, enabling the observation of changes in cell viability and function following exposure to various drugs or ionizing radiation. Complementarily, in vivo animal models offer a broader perspective, allowing for evaluating of both short- and long-term effects and a better understanding of chronic toxicity and cardiac diseases. By integrating these approaches, researchers can identify potential mechanisms of cardiotoxicity and devise effective prevention strategies. This analysis highlights the central role of preclinical models in advancing knowledge of cardiotoxic effects associated with common therapeutic regimens for thoracic and breast cancers.

• Book : 17(7)
• Pub. Date : 2025
• Page : pp.1059-1059
• Keyword :

• Book : 185()
• Pub. Date : 2025
• Page : pp.105698-105698
• Keyword :

북한의 핵⋅미사일 전력은 급속히 고도화되고 있으며, 핵전략 또한 억제를 넘어 핵전쟁 수행(nuclear war-fighting)에 중점을 두는 방향으로 진화하고 있다. 북한의 핵위협이 증대됨에 따라, 한국은 ‘3축체계’와 한미 ‘재래식핵통합’(CNI)을 기반으로 억제와 대응역량을 강화하는 데 주력하고 있다. 그러나 현재의 대응체계가 최적인지에 대한 면밀한 검토가 필요한 시점이다. 특히 전략사령부가 창설되어 3축체계를 지휘통제하게 됨에 따라, 이에 대한 재평가의 필요성은 더욱 커졌다.3축체계는 태생적으로 정체성이 불분명하여 전략⋅작전⋅전력의 연계성있는 대응체계 구축에 많은 문제점을 야기했으며, 억제력의 실효성 측면에서도 여러 취약점을 노출해왔다. 또한, 한미 연합작전체계와의 유기적 연계 방안이 부족하며, 한미 간 ‘방기와 연루’에 대한 우려로 인해 동맹 딜레마를 초래할 가능성도 내포하고 있다. 이러한 문제점을 고려하여, 본 논문은 3축체계의 재구성을 중심으로 현 북핵 대응체계를 재정립하고, 핵무장까지 전제로 한 장기적 청사진을 마련할 것을 제안한다.

• Book : 25(1)
• Pub. Date : 2025
• Page : pp.77-118
• Keyword :

• Book : 111(11)
• Pub. Date : 2025
• Page :
• Keyword :

Objectives/Goals: Radiation nephropathy results in morbidity and mortality in patients receiving cancer treatment. In addition, low birth weight and low nephron number are associated with increased risk for chronic kidney disease. This study examined the development and severity of radiation-induced renal hemodynamic dysfunction in a low renal mass mouse model. Methods/Study Population: Male mice (C57Bl/6, 8–12-weeks) were used to determine a suitable radiation dose regimen. Mice were subjected to fractionated bilateral kidney irradiation with 5–6 fractions of an X-ray dose of 0, 6, 8, and 10 Gy at 24-hr intervals using a CT-image-guided irradiator. Body weight and mortality were monitored for 5 weeks in mice. In a separate set of experiments, the low renal mouse model, ROP Os/+, and their normal counterpart, ROP +/+ mice were subjected to 5 fractionated bilateral kidney irradiations at 24-hr intervals with an X-ray dose of 6 Gy. Renal blood flow was assessed from renal artery resistive index (RRI) over 5 weeks post-irradiation using an ultrasound system. Transcutaneous measurement of FITC-sinistrin clearance was used to determine glomerular filtration rate (GFR). Results/Anticipated Results: The C57Bl/6 mice that received 5–6 fractions of 8 and 10 Gy had more than 50% mortality, while 100% of the mice exposed to 5 fractions of 6 Gy survived for 5 weeks. Body weight was also significantly decreased in mice exposed to 5 or 6 fractions of 8 or 10 but not 6 Gy radiation. Nonirradiated C57Bl/6, ROP +/+, and ROP Os/+ mice had similar baseline GFR and RRI. Irradiation of 5 fractions at 6 Gy decreased GFR and increased RRI in C57Bl/6 and ROP +/+ mice. Interestingly, following 5 fractions at 6 Gy irradiation ROP Os/+ mice had 25% lower GFR than wild-type ROP +/+ mice (946.3 ± 50.3 vs. 1232.9 ± 69.3 µL/min/100g BW, p Discussion/Significance of Impact: Our study determined a suitable fractionated bilateral kidney irradiation dose regimen to evaluate radiation nephropathy. Data demonstrated that fractionated bilateral kidney irradiation leads to decreased renal hemodynamics in mice. We also demonstrated that irradiation caused greater renal hemodynamic dysfunction in low renal mass mice.

• Book : 9(s1)
• Pub. Date : 2025
• Page : pp.174-174
• Keyword :

Abstract For fast neutron sources, such as compact neutron generators, it is desirable to have knowledge and ideally directly measure the energy spectrum of the generated neutrons. For neutrons, the produced radiation field, and the neutron energy spectrum, at a specific location from the source, can be altered by the distance to the source and become even significantly distorted by surrounding material — e.g. walls and the floor of the laboratory. To achieve this goal, we make use of the Time-of-Flight (ToF) technique, which has been implemented on the Timepix3 detector operated in highly integrated readout electronics as a miniaturized radiation camera MiniPIX-Timepix3. Equipped with a silicon sensor, the Timepix3 ASIC chip provides fast timing response of individual pixels at the nanosecond level. In this work, we use two Timepix3 detectors with a silicon sensor of thickness 300 μm and a segmented neutron conversion mask, intended for both thermal and fast neutrons and with a 65 μm thick silicon carbide (SiC) sensor. Demonstration and evaluation of the technique are provided by measurements with a compact neutron D-T pulsed generator at VSB-TU Ostrava laboratory which produces mono-energetic 14 MeV neutrons.

• Book : 20(03)
• Pub. Date : 2025
• Page : pp.C03045-C03045
• Keyword :

The presence of fungal spores in water poses a significant risk to public health, requiring effective inactivation strategies. Ultraviolet (UV) radiation is a widely used approach, traditionally employing mercury vapor lamps. However, these lamps have efficiency limitations and contain hazardous materials. As an alternative, ultraviolet light-emitting diodes (UV-LEDs) have emerged as a safer and more sustainable option. Despite their advantages, research on their efficacy against fungal spores remains limited. This study investigates the inactivation and post-exposure response of Aspergillus niger and Penicillium sp. spores using a collimated UV-LED system. The impact of two different wavelengths (265 nm and 280 nm) and post-treatment conditions (light and darkness for 24 h) on fungal viability was analyzed. Kinetic modeling was applied to assess the resistance of the spores and their capacity for photoreactivation. The results demonstrate that both the UV wavelength and the environmental conditions after exposure significantly influence disinfection outcomes. Penicillium sp. exhibited greater susceptibility to UV radiation but also higher photoreactivation potential, while A. niger showed stronger resistance and lower recovery capacity. The UV dose required for 99% inactivation, considering photoreactivation effects, was 323.7 ± 90.0 mJ cm−2 and 321.9 ± 43.8 mJ cm−2 for A. niger, whereas for Penicillium sp., it was 167.7 ± 13.0 mJ cm−2 and 146.5 ± 29.2 mJ cm−2 at 265 nm and 280 nm, respectively. These findings emphasize the necessity of tailoring UV-LED disinfection strategies based on the specific characteristics of the target organisms and post-treatment environmental factors.

• Book : 17(7)
• Pub. Date : 2025
• Page : pp.922-922
• Keyword :