Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel ...running showed over 60% reduction in tumor incidence and growth across five different tumor models. Microarray analysis revealed training-induced upregulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. Mechanistic analyses showed that NK cells were mobilized by epinephrine, and blockade of β-adrenergic signaling blunted training-dependent tumor inhibition. Moreover, epinephrine induced a selective mobilization of IL-6-sensitive NK cells, and IL-6-blocking antibodies blunted training-induced tumor suppression, intratumoral NK cell infiltration, and NK cell activation. Together, these results link exercise, epinephrine, and IL-6 to NK cell mobilization and redistribution, and ultimately to control of tumor growth.
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•Exercise reduces tumor incidence and growth in several mouse models•Exercise increases NK cell infiltration, thereby controlling tumor growth•Epinephrine mobilizes NK cells and β-blockade blunts the tumor suppression•Exercise-induced muscle-derived IL-6 is involved in NK cell redistribution
The beneficial effects of exercise are countless. Pedersen et al. now link exercise, cancer, and immunity and reveal that exercise decreases tumor incidence and growth by over 60% across several mouse tumor models through a direct regulation of NK cell mobilization and trafficking in an epinephrine- and IL-6-dependent manner.
Background
Electrochemotherapy is an established treatment for cutaneous tumors. This study aimed at determining efficacy of electrochemotherapy in recurrent head and neck cancer.
Methods
Phase II ...clinical trial in patients with recurrent head and neck carcinomas with no curative treatment options. Electrochemotherapy was performed under general anesthesia. Primary endpoint was tumor response (CT scanning) evaluated at week 8. Secondary endpoints included biopsy results, MRI and fluorodeoxyglucose‐positron emission tomography scanning, safety, toxicity, pain score, and quality‐of‐life questionnaires.
Results
Of 26 patients treated, 5 (19%) achieved complete response, 10 (39%) partial response, resulting in an objective response of 58%. Two responders remain without recurrence. No serious adverse events occurred during treatment. Four events occurred posttreatment: one bleeding episode, two episodes with mucosal swelling, and one patient died due to disease progression.
Conclusion
Electrochemotherapy is efficient against local recurrence of head and neck cancer with an overall response rate of 58%.
Background
Persons with cosmetic tattoos occasionally experience severe pain and burning sensation on magnetic resonance imaging (MRI).
Objective
To explore the culprit magnetic substances in ...commonly used permanent makeup inks.
Material and methods
20 inks used for cosmetic tattooing of eyebrows, eyeliners, and lips were selected. Ink bottles were tested for magnetic behavior with a neodymium magnet. Eight iron oxide inks qualified for the final study. Metals were analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP‐MS). The magnetic fraction of inks was isolated and analyzed by X‐ray fluorescence (XRF). Magnetic iron compounds were characterized by Mössbauer spectroscopy and powder X‐ray diffraction (XRD).
Results
ICP‐MS showed iron in all magnetic samples, and some nickel and chromium. Mössbauer spectroscopy and XRD detected ferromagnetic minerals, particularly magnetite, followed by goethite and hematite.
Conclusion
This original study of cosmetic ink stock products made with iron oxide pigments reports magnetic impurities in inks for cosmetic tattooing, e.g., magnetite, goethite, and hematite. These may be the main cause of MRI burn sensation in cosmetic tattoos. The mechanism behind sensations is hypothesized to be induction of electrical stimuli of axons from periaxonal pigment/impurity activated by magnetic force. Magnetite is considered the lead culprit.
Abstract Objective Follistatin-like 3 (fstl3), a natural inhibitor of members of the TGF-β family, increases during resistance training in human plasma. Fstl3 primarily binds myostatin and activin A, ...and thereby inhibits their functions. We hypothesize that blocking myostatin and activin A signalling through systemic fstl3 over-expression protects against diet-induced obesity and insulin resistance. Methods Fstl3 was over-expressed by DNA electrotransfer in tibialis anterior, quadriceps and gastrocnemius muscles in female C57BL/C mice, and the mice were subsequently randomized to chow or high-fat feeding. Body weight, food intake, fat accumulation by MR scanning, and glucose, insulin and glucagon tolerance were evaluated, as was the response in body weight and metabolic parameters to 24 h fasting. Effects of fstl3 on pancreatic insulin and glucagon content, and pancreatic islet morphology were determined. Results Fstl3 over-expression reduced fat accumulation during high-fat feeding by 16%, and liver fat by 50%, as determined by MRI. No changes in body weight were observed, while the weight of the transfected muscles increased by 10%. No transcriptional changes were found in the subcutaneous adipose tissue. Fstl3 mice displayed improved insulin sensitivity and muscle insulin signalling. In contrast, glucose tolerance was impaired in high-fat fed fstl3 mice, which was explained by increased hepatic glucagon sensitivity and glucose output, as well as a decrease in the pancreatic insulin/glucagon ratio. Accordingly, fstl3 transfection improved counter-regulation to 24 h fasting. Conclusion Fstl3 over-expression regulates insulin and glucagon sensitivities through increased muscular insulin action, as well as increased hepatic glucagon sensitivity and pancreatic glucagon content.
Adverse reactions in tattooed skin during magnetic resonance imaging (MRI) are rare but well known. Previous reports describe sudden burning pain in tattooed skin, sometimes accompanied by mild ...erythema and oedema when entering MRI scanners. The pathophysiology remains unclear, but simple direct thermal heating can be excluded. It has been hypothesized that MRI-triggered torque and traction create neural sensations from magnetic pigment particles. However, this case enlightens yet another possible mechanism. We present a 35-year-old woman experiencing reoccurring stinging sensations in three decorative black tattoos just seconds after the initiation of the MRI. Single-blind tests with handheld power magnets or a dummy could reproduce painful subjective feelings in her tattooed skin. Similar events were provoked during re-evaluation with MRI. Surprisingly, chemical analyses and electron microscopy of skin samples revealed carbon black as the colouring agent – no iron-based solids were detected. Our case demonstrates that MRI tattoo reactions are not limited to magnetic contaminants alone. More distinct subgroups of MRI-induced reactions may occur. We hypothesize that radiofrequency induction of surface currents in black carbon particles adjacent to sensory axons in the dermis may lead to neurosensations.
•No change in Gd-chelate relaxation rate after irradiation with high-energy X-rays.•Complete breakage of Gd-chelate by high-energy X-rays not detected.•In-vitro, complete breakage of Gd-chelate is ...below clinically relevant level.
With the introduction of hybrid magnetic resonance linacs (MR-linac), improved imaging has enabled daily treatment adaptation. However, the use of gadolinium based contrast agents (GBCAs) is desired to further improve MR image contrast. GBCAs are in the form of a non-toxic metalorganic gadolinium complex, but toxic un-chelated aqueous gadolinium(III), Gd3+(aq), can be released in patients if the organic ligand is degraded by the radiation. In this study, T1 relaxation measurements were performed to study the effect of radiation on three GBCAs.
GBCAs, gadoteric acid, gadobutrol and gadoxectic acid were investigated in a concentration range of 10–100 mM. Measurements were performed on a 500 MHz nuclear MR (NMR) spectrometer with a high-resolution inversion recovery sequence to determine T1. Samples were irradiated with 7 MV photons on an MR-linac to a total dose of 100 Gy. The lower detection limit of Gd3+(aq) was established by estimating the overall measurement uncertainty and comparing to corresponding changes in R1 when replacing chelated Gd3+ with gadolinium nitrate at predefined percentages.
The overall measurement uncertainty was estimated to ±0.0053 ms−1, corresponding to Gd3+(aq) detection levels 1%–1.5% or 1–4.5 micro molar at clinical GBCA dosage. No detectable differences in R1 were observed between irradiated and non-irradiated samples for any GBCA.
This study did not find any measurable degradation of GBCAs due to irradiation with high-energy X-rays, however, in-vivo investigations are needed to provide the clinical basis for safe use of contrast agents in a radiotherapy workflow.
Abstract
Background and study aims
Electrochemotherapy is an anticancer treatment that uses electric pulses to facilitate uptake of chemotherapeutic drugs in tumor cells and has proven to have a ...high local cytotoxic effect with minimal adverse events. Electrochemotherapy has mostly been used in treatment of cutaneous metastases but development of a new endoscopic electrode device has made treatment of colorectal tumors possible. This first-in-man multicenter phase I study investigated safety and efficacy of electrochemotherapy using endoscopic electroporation in patients with colorectal tumors.
Patients and methods
Seven patients with colorectal tumors who were deemed ineligible for or had declined standard treatment were included. They were treated with bleomycin either intratumorally or intravenously and the electric pulses were delivered through the endoscopic electrode device. Safety and efficacy were assessed clinically and by scans immediately after treatment and adverse events were reported. Response was evaluated up to 6 months after treatment by scans (magnetic resonance imaging or computed tomography) and endoscopic examinations.
Results
Seven patients aged 62 to 88 years with multiple comorbidities were included and had one or two treatments each. Post-treatment scans showed tumor responses in the treated areas and no damage to surrounding tissues. Only a few grade one adverse events were reported. Three patients had preoperative rectal bleeding, of which two reported cessation of bleeding and one reported decreased bleeding.
Conclusion
This first-in-man study shows that electrochemotherapy for colorectal tumors using the endoscopic electrode device can induce local tumor response and is safe also for fragile elderly patients with comorbidities.
Abstract Background The effects of physical exercise in patients with lacunar stroke, seem promising in secondary prevention and only few studies have investigated the effect of high-intensity ...interval training in patients with lacunar stroke. This study will be investigating whether high-intensity interval training improves cardiovascular fitness as well as cognitive- and endothelial function and potentially attenuating the risk of recurrent stroke. Methods A randomized controlled trial evaluating 12 weeks of home-based, high-intensity interval training compared with usual care. The intervention group will be exercising 15 min a day, 5 days a week, for 12 weeks. Outcomes will be evaluated at baseline, three, six and twelve months post-stroke with ‘The Graded Cycling Test with Talk Test’ as the primary outcome registered as power output in Watts. Additionally, an annually register-based follow-up will be performed for 5 years from date of inclusion with a composite endpoint of cardiovascular disease or death. Secondary outcomes will be: physical activity, endothelial response, mental well-being, cognition, mood, fatigue, stress, and MRI scan. Discussion This study is going to show if early initiated home-based high-intensity interval training is feasible and effective in patients with lacunar stroke. A self-chosen aerobic exercise modality allows a realistic implementation of practice, together with greater chance of long-term adherence. A limitation of the study is that recruitment bias cannot be ruled out, as there may be a preferential enrolment of patients who are self-motivated to engage in exercise.
Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel ...running showed significant exercise related reduction in tumor incidence and growth across several tumor models including transplantable tumors (Lewis lung and B16 melanoma), chemically (diethylnitrosamine (DEN) induced liver cancer, and a model of spontaneous melanoma (Tg(Grm1)EPv transgenic mice). Microarray analysis revealed exercise-induced up-regulation of pathways associated with immune function, prompting further investigations. NK cell infiltration was significantly increased in tumors from exercising mice, and depletion of NK cells by anti-asialo-GM1 administration increased tumor growth and blunted the exercise-dependent tumor suppression. Mechanistic analyses showed that NK cells were engaged through an epinephrine-dependent mobilization, and blockade of this response by ß-adrenergic blockade blunted the exercise-dependent tumor inhibition. Moreover, exercise-induced IL-6 facilitated redistribution of NK cells to peripheral tissues and induced a shift towards more cytotoxic (CD11b-, CD27+) NK cells at the tumor site. Together these results link exercise, epinephrine and IL-6 to NK cell mobilization and activation, and ultimately to improved control of tumor growth.
•In-treatment GTV reduction is not associated with treatment response.•In-treatment reduction in the viable tumour volume is related to better outcome.•ADC of the viable tumour volume is different in ...responders versus non-responders.
In radiotherapy, treatment response is generally evaluated many weeks after end of the treatment course. If the treatment outcome could be predicted during radiotherapy better tumour control could be achieved through timely adaptation of the treatment strategy. In this study intra-treatment change based on the diffusion MRI outlined viable tumour volume (VTV) was assessed and compared to the standard GTV to study their outcome prediction capacity.
Thirty-eight brain metastases from twenty-one cancer patients were analysed in this prospective trial. Diffusion and structural MRI was acquired on a 1 T machine before, during, and at follow-up 2–3 months after radiotherapy. The VTV was defined as a region with high cellularity using high b-value diffusion MRI scans. Further, the diffusivity of the VTV was derived as the apparent diffusion coefficient (ADC). Treatment outcome was determined using RECIST defined bounds in the T1W MRI follow-up scan. Longitudinal statistical analysis was performed using a linear mixed effect model.
The GTV declined in both responding and non-responding (significantly) tumours with inseparable rates during radiotherapy. The VTV volume fraction reduced significantly in the responding tumours only. The ADC of the VTV increased significantly in responding metastases whereas it decreased in non-responding metastases. Furthermore, no association between baseline tumour size or primary disease and outcome was observed.
GTV size change during radiotherapy is not a reliable predictor of outcome in brain metastases. On the other hand, change in the volume fraction of VTV and diffusivity of VTV shows ability to stratify treatment outcome.
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