EXTH-36. ELECTROCONVULSIVE SEIZURE-INDUCED CHANGES IN THE TUMOR MICROENVIRONMENT PROMOTE SURVIVAL IN GLIOMA-BEARING MICE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi171-vi171
Author(s):  
Timothy Sita ◽  
Lisa Hurley ◽  
Michael Drumm ◽  
Serena Tommasini-Ghelfi ◽  
Akanksha Mahajan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Progression ◽  
Relative Increase ◽  
Receptor Expression ◽  
Sodium Fluorescein ◽  
Sham Treatment ◽  
Histologic Evaluation ◽  
Bbb Permeability ◽  
Brain Parenchymal ◽  
Induced Changes

Abstract PURPOSE Growing evidence indicates that the neurotransmitters dysregulated in psychiatric disorders are similarly dysregulated in glioblastoma (GBM) biology. GBM cells are dependent on bountiful neuronal glutamate, utilize elevated dopamine receptor expression to augment progression, and catabolize serotonin to drive proliferation and inhibit anti-tumor immunity. The clinical induction of seizure, known as electroconvulsive therapy (ECT), has been used by psychiatrists since the 1930s to correct these dysregulations and can additionally improve medication blood-brain barrier (BBB) penetrance. We hypothesized that seizure-induced changes in the glioma microenvironment occur with ECT, slowing tumor progression, increasing BBB permeability, and prolonging overall survival in glioma-bearing mice. METHODS C57BL6 mice were orthotopically injected with CT-2A-Luc mouse glioma cells. Mice were randomized to receive ECT via ear-clip electrodes or sham treatment daily up to five times per week. Intracranial progression was monitored via bioluminescent signal from CT-2A-Luc xenografts. BBB permeability was assessed by subjecting mice to ECT or sham treatment immediately following intravenous injection of sodium fluorescein. RESULTS Intracranial progression was maximally reduced in ECT-treated mice relative to sham-treated mice after 17 ECT treatments (ECT radiance 2.6 x 109 photons/second versus sham 4.7 x 109 photons/second, p=0.013), which was further confirmed by both decreased tumor weight and tumor size on histologic evaluation. This translated into an improvement in overall survival from median 29 days in sham-treated mice to 38 days in ECT-treated mice (p=0.0018). Mean seizure duration was 41.8 seconds and positively correlated with overall survival (Pearson coefficient r=0.63, p=0.028). Brain parenchymal uptake of sodium fluorescein was significantly higher in ECT-treated mice (mean relative increase in ECS to sham radiance of 1.47, p< 0.05). CONCLUSION Repeated ECT slows tumor progression and prolongs overall survival in C57BL6 mice bearing CT-2A-Luc xenografts. The BBB is compromised immediately following ECT. ECT merits further oncologic investigation as a potential therapeutic in GBM.

scholarly journals Blocking Migration of Polymorphonuclear Myeloid-Derived Suppressor Cells Inhibits Mouse Melanoma Progression

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 726
Author(s):  
Christopher Groth ◽  
Ludovica Arpinati ◽  
Merav E. Shaul ◽  
Nina Winkler ◽  
Klara Diester ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Checkpoint Inhibitors ◽  
Suppressor Cells ◽  
Receptor Expression ◽  
Myeloid Derived Suppressor Cells ◽  
Melanoma Progression ◽  
Relative Contribution ◽  
Immunosuppressive Tumor Microenvironment ◽  
Metastatic Sites

Background: Despite recent improvement in the treatment of malignant melanoma by immune-checkpoint inhibitors, the disease can progress due to an immunosuppressive tumor microenvironment (TME) mainly represented by myeloid-derived suppressor cells (MDSC). However, the relative contribution of the polymorphonuclear (PMN) and monocytic (M) MDSC subsets to melanoma progression is not clear. Here, we compared both subsets regarding their immunosuppressive capacity and recruitment mechanisms. Furthermore, we inhibited PMN-MDSC migration in vivo to determine its effect on tumor progression. Methods: Using the RET transgenic melanoma mouse model, we investigated the immunosuppressive function of MDSC subsets and chemokine receptor expression on these cells. The effect of CXCR2 inhibition on PMN-MDSC migration and tumor progression was studied in RET transgenic mice and in C57BL/6 mice after surgical resection of primary melanomas. Results: Immunosuppressive capacity of intratumoral M- and PMN-MDSC was comparable in melanoma bearing mice. Anti-CXCR2 therapy prolonged survival of these mice and decreased the occurrence of distant metastasis. Furthermore, this therapy reduced the infiltration of melanoma lesions and pre-metastatic sites with PMN-MDSC that was associated with the accumulation of natural killer (NK) cells. Conclusions: We provide evidence for the tumor−promoting properties of PMN-MDSC as well as for the anti-tumor effects upon their targeting in melanoma bearing mice.

scholarly journals Impact of [18F]FDG-PET and [18F]FLT-PET-Parameters in Patients with Suspected Relapse of Irradiated Lung Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 279
Author(s):  
Tine N. Christensen ◽  
Seppo W. Langer ◽  
Gitte Persson ◽  
Klaus Richter Larsen ◽  
Annemarie G. Amtoft ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Fdg Pet ◽  
Tumor Volume ◽  
High Dose ◽  
Flt Pet ◽  
Pet Ct ◽  
Radiation Induced ◽  
Fdg Pet Ct ◽  
Induced Changes

Radiation-induced changes may cause a non-malignant high 2-deoxy-2-[18F]fluoro-d-glucose (FDG)-uptake. The 3′-deoxy-3′-[18F]fluorothymidine (FLT)-PET/CT performs better in the differential diagnosis of inflammatory changes and lung lesions with a higher specificity than FDG-PET/CT. We investigated the association between post-radiotherapy FDG-PET-parameters, FLT-PET-parameters, and outcome. Sixty-one patients suspected for having a relapse after definitive radiotherapy for lung cancer were included. All the patients had FDG-PET/CT and FLT-PET/CT. FDG-PET- and FLT-PET-parameters were collected from within the irradiated high-dose volume (HDV) and from recurrent pulmonary lesions. For associations between PET-parameters and relapse status, respectively, the overall survival was analyzed. Thirty patients had a relapse, of these, 16 patients had a relapse within the HDV. FDG-SUVmax and FLT-SUVmax were higher in relapsed HDVs compared with non-relapsed HDVs (median FDG-SUVmax: 12.8 vs. 4.2; p < 0.001; median FLT-SUVmax 3.9 vs. 2.2; p < 0.001). A relapse within HDV had higher FDG-SUVpeak (median FDG-SUVpeak: 7.1 vs. 3.5; p = 0.014) and was larger (median metabolic tumor volume (MTV50%): 2.5 vs. 0.7; 0.014) than the relapsed lesions outside of HDV. The proliferative tumor volume (PTV50%) was prognostic for the overall survival (hazard ratio: 1.07 pr cm3 [1.01–1.13]; p = 0.014) in the univariate analysis, but not in the multivariate analysis. FDG-SUVmax and FLT-SUVmax may be helpful tools for differentiating the relapse from radiation-induced changes, however, they should not be used definitively for relapse detection.

Fibronectin is overproduced by keloid fibroblasts during abnormal wound healing

1989 ◽  
Vol 9 (4) ◽  
pp. 1642-1650
Author(s):  
M Babu ◽  
R Diegelmann ◽  
N Oliver
Keyword(s):  
Wound Healing ◽  
State Level ◽  
Cell Types ◽  
Relative Increase ◽  
Receptor Expression ◽  
Glucocorticoid Treatment ◽  
Fibronectin Receptor ◽  
Coordinate Regulation ◽  
Extracellular Matrix Components ◽  
Keloid Fibroblasts

Wound healing in certain individuals leads to the development of keloid tumors which exhibit abnormal collagen metabolism and an increased abundance of extracellular matrix components. Comparison of fibronectin levels in fibroblasts derived from keloids and normal dermis revealed a relative increase in intracellular and extracellular fibronectin in the keloid-derived cells. While fibronectin was similarly processed, compartmentalized, and degraded by both cell types, fibronectin biosynthesis was found to be accelerated as much as fourfold in keloid fibroblasts due to a corresponding increase in the amount of accumulated fibronectin mRNA. These changes account for the elevated steady-state level of the molecule in keloid fibroblasts and suggest that increased fibronectin in keloid lesions is due to overproduction by the wound-healing fibroblasts. Glucocorticoid treatment stimulated fibronectin biosynthesis in both normal and keloid fibroblasts. However, the amount of stimulation was less for the keloid-derived cells, indicating a limitation on maximal rates of fibronectin biosynthesis. These observations suggest that separate mechanisms act to control basal and maximal rates of fibronectin production. Biosynthesis of the 140-kilodalton fibronectin receptor was also found to be increased in keloid fibroblasts, suggesting some level of coordinate regulation for fibronectin and fibronectin receptor expression.

Effectiveness and safety of eribulin for human epidermal growth factor receptor 2 negative metastatic breast cancer in a real-world population

2021 ◽  
pp. 107815522110382
Author(s):  
Rocío Díaz-Acedo ◽  
Silvia Artacho Criado ◽  
Rocío Jiménez Galán ◽  
Antonio Gutiérrez Pizarraya ◽  
Mercedes Galván Banqueri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Confidence Interval ◽  
Median Overall Survival ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

Background Eribulin’s clinical benefit remains unclear; so, studies analyzing its effectiveness in routine clinical practice are interesting. Patients and methods This is a multicenter, retrospective study including patients with human epidermal growth factor receptor-2-negative metastatic breast cancer which assesses effectiveness and safety of eribulin. Results A total of 140 women were included, with a median age of 57 years. The median overall survival and progression-free survival were 8.8 (95% confidence interval: 6.1–11.4) and 2.8 months (95% confidence interval: 2.5–3.1), respectively. For patients with hormonal receptor expression, a significantly longer progression-free survival was observed: 3.4 (95%confidence interval: 2.3–4.5) versus triple negative: 2.0 (95%confidence interval: 1.7–2.3) months, p = 0.003. Also, those who had received capecitabine prior to eribulin had a higher median overall survival than those who had not received it (9.5 months, 95% confidence interval: 6.6–12.5 vs. 4.8 months, 95% confidence interval: 3.4–6.2; p = 0.001). When only triple-negative patients were included, median overall survival was 6.5 (95% confidence interval: 0.1–16.2) for those who had received previous capecitabine versus 4.3 (95% confidence interval: 2.8–5.8) months for patients who had not received it; p =0.006. The safety profile of eribulin was adequate. Conclusion Effectiveness of eribulin in a real-life human epidermal growth factor receptor-2--negative population is lower than that observed in clinical trials. Its benefit seems to be higher in patients with hormonal receptor expression and patients who had received capecitabine prior to eribulin. The safety profile of eribulin is adequate.

The Value of Positron Emission Tomography for Differentiating Brain Tumor Progression and Treatment-Induced Changes

2020 ◽  
pp. 1067-1081
Author(s):  
Bart R. J. van Dijken ◽  
Roelien H. Enting ◽  
Hanne-Rinck Jeltema ◽  
Miranda C. A. Kramer ◽  
Rudi A. J. O. Dierckx ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Tumor ◽  
Tumor Progression ◽  
Emission Tomography ◽  
Positron Emission ◽  
Induced Changes

Daidzein affects steroidogenesis and oestrogen receptor expression in medium ovarian follicles of pigs

2013 ◽  
Vol 61 (1) ◽  
pp. 85-98 ◽  
Author(s):  
Anna Nynca ◽  
Dominika Słonina ◽  
Olga Jablońska ◽  
Barbara Kamińska ◽  
Renata Ciereszko
Keyword(s):  
Protein Expression ◽  
Granulosa Cells ◽  
Oestrogen Receptor ◽  
Receptor Expression ◽  
Progesterone Production ◽  
Progesterone Secretion ◽  
Mrna And Protein Expression ◽  
Induced Changes ◽  
Reproductive Processes

Daidzein, a phytoestrogen present in soybean products used in swine feed, has been demonstrated to affect both reproductive and endocrine functions. The aims of this study were to examine the in vitro effects of daidzein on (1) progesterone (P4) and oestradiol (E2) secretion by porcine luteinised granulosa cells harvested from medium follicles, and (2) the mRNA and protein expression of oestrogen receptors α and β (ERα and ERβ) in these cells. The influence of E2 on P4 secretion and ERα and ERβ expression in the granulosa cells of pigs was also investigated. It was found that daidzein inhibited progesterone secretion by luteinised granulosa cells isolated from medium follicles. In contrast, E2 did not affect progesterone production by these cells. Moreover, daidzein did not alter the granulosal secretion of E2. Both daidzein and E2 decreased mRNA expression of ERα in the cells examined. The expression of ERβ mRNA was not affected by daidzein but was inhibited by E2. ERα protein was not detected while ERβ protein was found in the nuclei of the cells. Daidzein and E2 upregulated the expression of ERβ protein in the cells. In summary, the phytoestrogen daidzein directly affected the porcine ovary by inhibiting progesterone production and increasing ERβ protein expression. Daidzein-induced changes in follicular steroidogenesis and granulosal sensitivity to oestrogens may disturb reproductive processes in pigs.

scholarly journals ELISA study of matrix metalloproteinases 2, 7, 9 and their type 2 tissue inhibitor in the tumors of gastric cancer patients: clinical and pathologic correlations

2018 ◽  
Vol 46 (4) ◽  
pp. 323-329
Author(s):  
E. S. Gershtein ◽  
A. A. Ivannikov ◽  
V. L. Chang ◽  
N. A. Ognerubov ◽  
М. M. Davydov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Matrix Metalloproteinases ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Gastric Cancer Patients

Background: Over the last 10 years the incidence of gastric cancer has declined significantly. Nevertheless, it remains one of the most prevalent malignancies both in Russia and worldwide. Therefore, the problems of early diagnostics, prognosis and individualized treatment choice are still on the agenda. Much attention is paid to the evaluation of molecular biological characteristics of the tumor, as well as to the development of multiparametric prognostic systems for gastric cancer based on its identified characteristics. An important place among potential tumor biological markers belongs to matrix metalloproteinases (MMPs) involved into all the stages of tumor progression, first of all, into the regulation of invasion and metastasizing.Aim: Comparative quantitative evaluation of some MMP family members (MMP-2, 7, and 9) and one of the tissue MMP inhibitors (TIMP-2) levels in the tumors and adjacent histologically unchanged mucosa in gastric cancer patients, the analysis of their associations with the main clinical and pathological features of the disease and its prognosis.Materials and methods: Sixty six (66) primary gastric cancer patients (32 male and 34 female) aged 24 to 82 years (median, 61 year) were recruited into the study. Twenty two (22) patients were with stage I of the disease, 11 with stage II, 28 with stage III, and 5 with stage IV. The concentrations of the proteins studied were measured in the tumor and unchanged mucosa extracts by standard direct ELISA kits (Quantikine®, R&D Systems, USA).Results: Tumor MMP-2, 7 and 9 levels were significantly increased, compared to those in the adjacent histologically unchanged mucosa, in 80, 70 and 72% of gastric cancer patients, respectively, while the increase of TIMP-2 level found in 61% of the tumors was not statistically significant. Tumor MMP-2 and TIMP-2 content was increasing significantly with higher T index – size and advancement of the primary tumor (p < 0.01 and p < 0.05 respectively). Tumor MMP-2 level was also increasing in parallel with the N index (regional lymph node involvement; p < 0.01); it was significantly higher in the patients with distant metastases than in those without them (p < 0.05). Tumor MMP-9 and MMP-7 concentrations were not significantly associated with the indices of the tumor progression. The patients were followed up for 1 to 85 months (median, 18.3 months). According to the univariate analysis, high (> 32.6 ng/mg protein) MMP-2 and low MMP-7 (< 1.1 ng/mg protein) levels in the gastric cancer tissue represent statistically significant unfavorable prognostic factors for overall survival. Increased TIMP-2 level is associated with a non-significant decrease in the overall survival (p > 0.05), whereas the MMP-9 level was unrelated to the gastric cancer prognosis. Only T index (p = 0.0034) and tumor MMP-7 content (p = 0.026) remained independent prognostic factors in the multivariate regression analysis.Conclusion: The majority of gastric cancer patients demonstrate a significant increase in the expression of three MMP family members, i.e. gelatinases (MMP-2 and 9), and matrilysin (MMP-7), in the tumors, as compared to adjacent histologically unchanged mucosa. Only MMP-2 levels were associated with the disease progression, increasing with higher TNM system indices. High MMP-2 and low MMP-7 content in the gastric cancer tissue are significant unfavorable prognostic factors for the overall survival in the univariate analysis, but only MMP-7 has retained its independent prognostic value in the multivariate assessment.

Exercise- and cold-induced changes in plasma beta-endorphin and beta-lipotropin in men and women

1987 ◽  
Vol 62 (2) ◽  
pp. 622-627 ◽  
Author(s):  
M. Viswanathan ◽  
J. P. Van Dijk ◽  
T. E. Graham ◽  
A. Bonen ◽  
J. C. George
Keyword(s):  
Exercise Bout ◽  
Bicycle Ergometer ◽  
Relative Increase ◽  
Thermoregulatory Response ◽  
O2 Uptake ◽  
Beta Endorphin ◽  
Exposure Levels ◽  
Induced Changes ◽  
Ergometer Test ◽  
Bicycle Ergometer Test

The plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) response of men, eumenorrheic women, and amenorrheic women (n = 6) to 1 h of rest or to a bicycle ergometer test [20 min at 30% maximum O2 uptake (VO2max), 20 min at 60% VO2max, and at 90% VO2max to exhaustion] was studied in both normal (22 degrees C) and cold (5 degrees C) environments. beta-EP and beta-LPH was measured by radioimmunoassay in venous samples collected every 20 min during rest or after each exercise bout. Exhaustive exercise at ambient temperature (Ta) 22 degrees C induced significant increases in plasma beta-EP and beta-LPH in all subjects as did work at 60% VO2max in amenorrheic and eumenorrheic women. During work at Ta 5 degrees C, the relative increase in beta-EP and beta-LPH was suppressed in eumenorrheic women and completely prevented in amenorrheic women. Although significant lowering of beta-EP and beta-LPH was observed in men and eumenorrheic women during rest at 5 degrees C, amenorrheic women maintained precold exposure levels. These findings suggest that plasma beta-EP and beta-LPH may reflect a thermoregulatory response to heat load. There appears to be a sexual dimorphism in exercise- and cold-induced release of beta-EP and beta-LPH and amenorrhea may be accompanied by alterations in these responses.

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