Purpose: The aim of this study was to determine whether moderate hyperthermic doses, routinely encountered in the periablational zone during thermal ablation, activate tumor cells sufficiently to secrete pro-tumorigenic factors that can induce increased proliferation.Material and methods: R3230 rat mammary tumor cells and human cancer cell lines, MCF7 breast adenocarcinoma, HepG2 and Huh7 HCC, and HT-29 and SW480 colon adenocarcinoma, were heated in to 45 ± 1 °C or 43 ± 1 °C in vitro for 5-10 min and incubated thereafter at 37 °C for 1.5, 3 or 8 hr (n = 3 trials each; total N = 135). mRNA expression profiles of cytokines implicated in RF-induced tumorigenesis including IL-6, TNFα, STAT3, HGF, and VEGF, were evaluated by relative quantitative real-time PCR. HSP70 was used as control. c-Met and STAT3 levels were assessed by Western blot. Finally, naïve cancer cells were incubated with medium from R3230 and human cancer cells that were subjected to 43-45 °C for 5 or 10 min and incubated for 3 or 8 h at 37 °C in an xCELLigence or incuCyte detection system.Results: Cell-line-specific dose and time-dependent elevations of at least a doubling in HSP70, IL-6, TNFα, STAT3, and HGF gene expression were observed in R3230 and human cancer cells subjected to moderate hyperthermia. R3230 and several human cell lines showed increased phosphorylation of STAT3 3 h post-heating and increased c-Met following heating. Medium of cancer cells subject to moderate hyperthermia induced statistically significant accelerated cell growth of all cell lines compared to non-heated media (p < 0.01, all comparisons).Conclusion: Heat-damaged human tumor cells by themselves can induce proliferation of tumor by releasing pro-tumorigenic factors.
Publications
2020
Feasibility, safety, and utility of brain MRI for patients with non-MRI-conditioned cardiac implantable electrical devices (CIEDs) remains controversial. While a growing number of studies have shown safe employment in select patients under strict protocols, there is an increasing clinical need for further off-label investigations. To assess the feasibility and utility of brain MRI in neurological and neurosurgical patients with non-MRI-conditioned CIEDs using off-label protocol. We retrospectively evaluated 126 patients with non-MRI-conditioned CIEDs referred to our hospital between 2014 to 2018 for MRI under an IRB-approved protocol. A total of 126 off-label brain MRI scans were performed. The mean age was 67.5 ± 13.0. Seventy percent of scans were performed on female patients. Indications for MRI are neurosurgical (45.2%), neurological (51.6%), and others (3.2%). MRI utilization for tumor cases was highest for tumor cases (68.3%), but employment was valuable for vascular (12.7%), deep brain stimulators (3.2%), and other cases (15.9%). In the tumor category, (37.2%) of the scans were performed for initial diagnosis and pre-surgical planning, (47.7%) for post-intervention evaluation/surveillance, (15.1%) for stereotactic radiosurgery treatment (CyberKnife). No clinical complications were encountered. No functional device complications of the CIED were identified during and after the MRI in 96.9% of the studies. A 49.6% of the off-label brain MRI scans performed led to a clinically significant decision and/or intervention for the patients. A 42.9% of obtained MRI studies did not change the plan of care. A 7.9% of post-scan decision-making data was not available. We demonstrate that off-label brain MRI scans performed on select patients under a strict protocol is feasible, safe, and relevant. Almost 50% of scans provided critical information resulting in clinical intervention of the patients.
RATIONALE AND OBJECTIVES: To analyze the performances of diameter-based measurements, either using diameters, or by calculating diameter-based volumes, as compared to volume measurements in assessing growth of pulmonary adenocarcinomas manifesting as subsolid nodules on CT.
MATERIALS AND METHODS: In this IRB-approved, retrospective study, 74 pulmonary adenocarcinomas presenting as subsolid nodules and resected in 69 patients (21 men, 48 women, mean age 70 ± 9 years) were included. Three CTs were available for each patient. Nodule size on each CT was assessed with diameter measurements, calculated volume based on diameter measurements, and measured volume. Nodule growth was defined as an increase of measured volume ≥25% between two sequential CTs. Sensitivity, specificity, accuracy, positive and negative predictive values of diameter-based measurements for growth assessment were calculated. Nodule characteristics were compared with nonparametric tests and analysis of variance.
RESULTS: There were fewer growing nodules during CT1-CT2 interval (n = 22, 30%) than during CT2-CT3 interval (n = 33, 45%, p =.060). Specificity and negative predictive value of diameter-based measurements for growth assessment ranged respectively from 52 to 77% and 81 to 83% between CT1 and CT2, and from 66 to 76% and 79 to 90% between CT2 and CT3. Nongrowing nodules tended to be larger, regardless how size was measured, and some of these differences in size were statistically significant (p =.002 to .046).
CONCLUSION: For pulmonary adenocarcinomas presenting as subsolid nodules on CT, diameter-based assessment of nodule volume is reasonably accurate at confirming a lack of nodule growth but may overestimate actual growth, as compared to growth assessment based on measured volume.