Effect of plan complexity on the dosimetry, delivery accuracy, and interplay effect in lung VMAT SBRT with 6 MV FFF beam.

PURPOSE: The purpose of this study is to investigate the effect of plan complexity on the dosimetry, delivery accuracy, and interplay effect in lung stereotactic body radiation therapy (SBRT) using volumetric modulated arc therapy (VMAT) with 6 MV flattening-filter-free (FFF) beam. METHODS: Twenty patients with early stage non-small cell lung cancer were included. For each patient, high-complexity (HC) and low-complexity (LC) three-partial-arc VMAT plans were optimized by adjusting the normal tissue objectives and the maximum monitoring units (MUs) for a Varian TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, CA, USA) using 6 MV FFF beam. The effect of plan complexity was comprehensively evaluated in three aspects: (1) The dosimetric parameters, including CI, D2cm, R50, and dose-volume parameters of organs at risk were compared. (2) The delivery accuracy was assessed by pretreatment quality assurance for two groups of plans. (3) The motion-induced dose deviation was evaluated based on point dose measurements near the tumor center by using a programmable phantom. The standard deviation (SD) and maximum dose difference of five measurements were used to quantify the interplay effect. RESULTS: The dosimetry of HC and LC plans were similar except the CI (1.003 ± 0.032 and 1.026 ± 0.043, p = 0.030) and Dmax to the spinal cord (10.6 ± 3.2 and 9.9 ± 3.0, p = 0.012). The gamma passing rates were significantly higher in LC plans for all arcs (p < 0.001). The SDs of HC and LC plans ranged from 0.5-16.6% and 0.03-2.9%, respectively, under the conditions of one-field, two-field, and three-field delivery for each plan with 0.5, 1, 2, and 3 cm motion amplitudes. The maximum dose differences of HC and LC plans were 34.5% and 9.1%, respectively. CONCLUSION: For lung VMAT SBRT, LC plans have a higher delivery accuracy and a lower motion-induced dose deviation with similar dosimetry compared with HC plans.

Phytic acid-modified CeO2 as Ca2+ inhibitor for a security reversal of tumor drug resistance.

Ca2+ plays critical roles in the development of diseases, whereas existing various Ca regulation methods have been greatly restricted in their clinical applications due to their high toxicity and inefficiency. To solve this issue, with the help of Ca overexpressed tumor drug resistance model, the phytic acid (PA)-modified CeO2 nano-inhibitors have been rationally designed as an unprecedentedly safe and efficient Ca2+ inhibitor to successfully reverse tumor drug resistance through Ca2+ negative regulation strategy. Using doxorubicin (Dox) as a model chemotherapeutic drug, the Ca2+ nano-inhibitors efficiently deprived intracellular excessive free Ca2+, suppressed P-glycoprotein (P-gp) expression and significantly enhanced intracellular drug accumulation in Dox-resistant tumor cells. This Ca2+ negative regulation strategy improved the intratumoral Dox concentration by a factor of 12.4 and nearly eradicated tumors without obvious adverse effects. Besides, nanocerias as pH-regulated nanozyme greatly alleviated the adverse effects of chemotherapeutic drug on normal cells/organs and substantially improved survivals of mice. We anticipate that this safe and effective Ca2+ negative regulation strategy has potentials to conquer the pitfalls of traditional Ca inhibitors, improve therapeutic efficacy of common chemotherapeutic drugs and serves as a facile and effective treatment platform of other Ca2+ associated diseases. Electronic Supplementary Material: Supplementary material (further details of the XRD pattern of CeO2, TEM images, XPS spectra, cellular uptake study, cytotoxicity data, apoptosis study, biodistribution, and biosecurity of nanocerias in vivo, etc.) is available in the online version of this article at 10.1007/s12274-022-4069-0.

Case Report: Variety of Target Antigens During 1 Year Follow-Up of a Patient Initially Diagnosed With Bullous Pemphigoid.

Autoimmune bullous diseases (AIBDs), presenting cutaneous and/or mucosal bullous lesions, are classified into pemphigus and pemphigoid diseases. A longtime observation for complicated AIBD cases is rarely reported. In this study, serum samples of one AIBD patient were collected at seven different time points during the disease course including a relapse, which were examined by our conventional and newly developed methods for the detection of autoantibodies. Interestingly, we found changes of both the presence and the titers of various autoantibodies in accordance with the changes of clinical features during the whole disease course, which indicated that the patient started as bullous pemphigoid and relapsed as concurrence of bullous pemphigoid and mucosal-dominant-type pemphigus vulgaris.

Picrasidine N Is a Subtype-Selective PPARß/δ Agonist.

Recently, growing evidence of the pivotal roles of peroxisome proliferator-activated receptor (PPAR) ß/δ in various physiological functions, including lipid homeostasis, cancer, and inflammation, has raised interest in this receptor. In this study, the naturally occurring dimeric alkaloid picrasidine N (1) from Picrasma quassioides was identified as a novel PPARß/δ agonist from a library consisting of plant extracts and natural compounds using a mammalian one-hybrid assay, and this compound was characterized. Compound 1 activated PPARß/δ but did not activate or slightly activated PPARα and PPARγ. Furthermore, a peroxisome proliferator response element-driven luciferase reporter gene assay demonstrated that 1 enhanced PPARß/δ transcriptional activity. Moreover, 1 selectively induced mRNA expression of ANGPTL4, which is a PPAR target gene. This observation is quite different from previously identified synthetic PPARß/δ agonists, which can induce the expression of not only ANGPTL4 but also other PPAR target genes, such as ADRP, PDK4, and CPT-1. These results demonstrate that 1 is a potent subtype-selective and gene-selective PPARß/δ agonist, suggesting its potential as a lead compound for further drug development. This compound would also be a useful chemical tool for elucidating the mechanism of PPARß/δ-regulated specific gene expression and the biological significance of PPARß/δ.

The synergistic effects of traditional Chinese herbs and radiotherapy for cancer treatment.

Traditional Chinese medicine (TCM) has been demonstrated to have potent cytotoxic activity against certain malignant tumors. Ionizing radiation (IR) is one of the most effective methods used in the clinical treatment of cancer. The drawback of a single formula is that it limits the treatment efficacy for cancer, while comprehensive strategies require additional theoretical support. However, a combination of different antitumor treatment modalities is advantageous in restricting the non-specific toxicity often observed with an extremely high dose of a single regimen. The induction of apoptotic cell death is a significant process in tumor cells following radiotherapy or chemotherapy, and resistance to these treatments has been linked to a low propensity for apoptosis. Autophagy is a response of cancer cells to IR or chemotherapy, and involves the prominent formation of autophagic vacuoles in the cytoplasm. In this review, the synergistic effects of TCM and radiotherapy are summarized and the underlying mechanisms are illustrated, providing new therapeutic strategies for cancer.

Insulin-like growth factor-1 fused with thrombopoietin mimetic peptide effectively increase platelets count in vivo.

OBJECTIVE: To design the expression of fusion proteins containing one or 2 thrombopoietin mimetic peptide (TMP). METHODS: This study was conducted at Harbin Pharmaceutical Group Research and Development Center, Harbin, China from June 2009 to January 2010. We designed the protein that was fused to the C-terminus of insulin-like growth factors (IGF-1) by a flexible peptide linker by Dami cell proliferation assay, colony-forming assay, and analysis of platelet in mice to prove our hypothesis. The total number of mice used was 48 in all 4 groups. RESULTS: The fusion proteins were produced in Escherichia coli BL21 (DE3) at up to 26% of the total cell proteins. Subsequent biological activity assays showed that the fusion proteins exhibited higher potency than recombinant human thrombopoietin (TPO). Our results showed that the fusion proteins IGF-1-TMP exhibited higher biological activities than TMP in Dami cell proliferation, human cord blood cell colony-forming assays, and in experiments on acute myeloid radiation sickness mice, which can effectively increase the number of platelets. CONCLUSION: Experiments in mice and biology activity assay, which can effectively increase the number of platelets, indicated that it has a potential role in pharmaceutical applications for the treatment of thrombocytopenia.

PET imaging of acute and chronic inflammation in living mice.

PURPOSE: In this study, we evaluated the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced acute and chronic inflammation in living mice by PET imaging of TNF-alpha and integrin alpha(v)beta(3) expression. METHODS: TPA was topically applied to the right ear of BALB/c mice every other day to create the inflammation model. (64)Cu-DOTA-etanercept and (64)Cu-DOTA-E{E[c(RGDyK)](2)}(2) were used for PET imaging of TNF-alpha and integrin alpha(v)beta(3) expression in both acute and chronic inflammation. Hematoxylin and eosin staining, ex vivo autoradiography, direct tissue sampling, and immunofluorescence staining were also performed to confirm the non-invasive PET imaging results. RESULTS: The ear thickness increased significantly and the TNF-alpha level more than tripled after a single TPA challenge. MicroPET imaging using (64)Cu-DOTA-etanercept revealed high activity accumulation in the inflamed ear, reaching 11.1 +/- 1.3, 13.0 +/- 2.0, 10.9 +/- 1.4, 10.2 +/- 2.2%ID/g at 1, 4, 16, and 24 h post injection, respectively (n = 3). Repeated TPA challenges caused TPA-specific chronic inflammation and reduced (64)Cu-DOTA-etanercept uptake due to lowered TNF-alpha expression. (64)Cu-DOTA-E{E[c(RGDyK)](2)}(2) uptake in the chronically inflamed ears (after four and eight TPA challenges) was significantly higher than in the control ears and those after one TPA challenge. Immunofluorescence staining revealed increased integrin beta(3) expression, consistent with the non-invasive PET imaging results using (64)Cu-DOTA-E{E[c(RGDyK)](2)}(2) as an integrin alpha(v)beta(3)-specific radiotracer. Biodistribution and autoradiography studies further confirmed the quantification capability of microPET imaging. CONCLUSION: Successful PET imaging of TNF-alpha expression in acute inflammation and integrin alpha(v)beta(3) expression in chronic inflammation provides the rationale for multiple target evaluation over time to fully understand the inflammation processes.