A Population-Based Tumor-Volume Model for Head and Neck Cancer During Radiation Therapy With a Dynamic Oxygenated Compartment.

PURPOSE: With the coming era of digital medicine and healthcare technology, mathematical modeling of tumors has become a key step to optimize and realize precision radiation therapy. The purpose of this study was to develop a mathematical model for simulating the change of head and neck (HN) tumor volume during radiation therapy. METHODS AND MATERIALS: A formula was developed to describe the dynamic change of oxygenated compartment within a tumor, which was combined with the lethal lesions model to describe various cell processes during radiation therapy, including potentially lethal lesion repair and misrepair, cell proliferation/loss, and tumor reoxygenation. Parameter sensitivity analysis was performed to evaluate the impacts of lesion- and repair-related biological factors on radiation therapy outcomes. RESULTS: We tested our model on 14 available patients with HN cancer and compared the performance with 3 other models. The mean error of our model for the 12 good fit cases was 12.2%, which is considerably smaller than that of the linear quadratic model (19.7%), the generalized linear quadratic model (19.1%), and a 4-level cell population model (16.6%). Correlation analysis results revealed that for small tumors, there was a positive correlation (correlation coefficient r=0.9416) between hypoxic fraction (hf) and tumor volume, whereas the correlation became negative and not significant (r=-0.4365) for large tumors. It is demonstrated from sensitivity analysis that the production rate of lethal lesions (ηl) has a far greater impact on tumor volume than other parameters. The hf had an insignificant impact on tumor volume but had a notable influence on the volume of surviving cells. The final volume of surviving cells athf=0.5 was almost 8 ×102 times that of hf=0.01. The potentially lethal lesion-related parameters (the production rate of potentially lethal lessions per unit dose ηpl, the rate of correct repair per unit time εpl, and the rate of binary misrepair per unit time ε2pl) had rather small impacts (<1%) on both tumor volume and the volume of surviving cells, which indicates that the repaired and misrepaired sublethal cells only take up a small portion of the total cancer cell population. CONCLUSIONS: A population-based tumor-volume model for HN cancer during radiation therapy with a dynamic oxygenated compartment was developed in this study. Comprehensively considering the damage process of tumor cells caused by radiation therapy, the accurate prediction of the volume change of HN tumors during treatment was revealed. Meanwhile, various cell activities and their principles in the process of antitumor treatment were reflected, which has positive clinical reference significance for radiobiology.

Discovery of a small-molecule NDR1 agonist for prostate cancer therapy.

Prostatic cancer (PCa) is a common malignant neoplasm in men worldwide. Most patients develop castration-resistant prostate cancer (CRPC) after treatment with androgen deprivation therapy (ADT), usually resulting in death. Therefore, investigating new therapeutic targets and drugs for PCa patients is urgently needed. Nuclear Dbf2-related kinase 1 (NDR1), also known as STK38, is a serine/threonine kinase in the NDR/LATS kinase family that plays a critical role in cellular processes, including immunity, inflammation, metastasis, and tumorigenesis. It was reported that NDR1 inhibited the metastasis of prostate cancer cells by suppressing epithelial-mesenchymal transition (EMT), and decreased NDR1 expression might lead to a poorer prognosis, suggesting the enormous potential of NDR1 in antitumorigenesis. In this study, we characterized a small-molecule agonist named aNDR1, which specifically bound to NDR1 and potently promoted NDR1 expression, enzymatic activity and phosphorylation. aNDR1 exhibited drug-like properties, such as favorable stability, plasma protein binding capacity, cell membrane permeability, and PCa cell-specific inhibition, while having no obvious effect on normal prostate cells. Meanwhile, aNDR1 exhibited good antitumor activity both in vitro and in vivo. aNDR1 inhibited proliferation and migration of PCa cells and promoted apoptosis of PCa cells in vitro. We further found that aNDR1 inhibited subcutaneous tumors and lung metastatic nodules in vivo, with no obvious toxicity to the body. In summary, our study presents a potential small-molecule lead compound that targets NDR1 for clinical therapy of PCa patients.

Value of the virtual monoenergetic image from dual-layer dual-energy computed tomography enterography in the preoperative assessment of the internal penetrating complication of Crohn's disease.

BACKGROUND: To determine the utility of virtual-monoenergetic imaging (VMI) at low energy levels from contrast-enhanced dual-layer dual-energy (DLDE) computed tomography enterography (CTE) in the preoperative assessment of internal penetrating lesions of Crohn's disease (CD). MATERIALS AND METHODS: Thirty-eight patients with penetrating lesions of CD by surgery undergoing contrast-enhanced DLDE CTE were retrospectively included. Polyenergetic imaging (PEI) and VMIs at low energy levels [40-70 kiloelectron volts (keV)] with 10 keV intervals were reconstructed. The objective parameters of image quality [noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)] and the subjective parameter of image quality [diagnostic performance of lesions (DPL), overall image quality(OIQ)] of PEI and all VMIs at the low energy level were compared to determine the VMI on the optimal energy level. The lesion detection capability between PEI and the optimal VMI was compared. RESULTS: VMI40 was determined to be the optimal VMI among all VMIs at the low energy level for owning the best image quality. No significant difference was found in the detecting capability in penetrating lesions between VMI40 and PEI (p = 1.0), whereas a significant difference was found in the detecting capability in the bowel origin of the penetrating lesions (p = 0.004), the involved organ or structure by the fistula (p = 0.016) and the orifice of the fistula connected to the involved organ or structure ( p = 0.031) between them. CONCLUSIONS: Compared to conventional PEI, VMI40 improves the detection capability in anatomical details of penetrating lesions of CD, helping colorectal surgeons rationalizing preoperative plans of internal penetrating lesions of CD.