scholarly journals Serum IL‐6 and MCP‐1 concentrations in dogs with lymphoma before and after doxorubicin treatment as a potential marker of cellular senescence

Author(s):  
Brittany L. Evans ◽  
Joelle M. Fenger ◽  
Greg Ballash ◽  
Megan Brown

Author(s):  
Shreshth Rajan

Chemotherapy-related deaths, the result of treatment with faulty medications, account for nearly 10% of all breast cancer deaths (Rashbass, 2016). Patient-specific, personalized medicine is evidently required to administer optimized therapeutics and prevent treatment-related mortality. In order to develop a predictive model for breast cancer therapy, the following study analyzed the mRNA data of 4,704 genes derived from 20 breast cancer patients before and after doxorubicin treatment for 16 weeks (O’brien et al., 2006; Perou et al., 2000). The genomic data of each patient was first stratified into 9 groups (corresponding to the 9 Mechanisms defined in Figure 4) based on mRNA expression in response to the tumor and to the doxorubicin treatment. The study then employed the Planckian Distribution Equation (PDE) discovered at Rutgers University to model the stratified samples by transforming each mechanism into a single long-tailed histogram fitted by the PDE. Our PDE model is based on 3 parameters - A, B, and C - of which 2 were extracted from each model to generate the plots seen in figures 5e and 5f. The drug-induced slopes of the A vs C plots were then determined for all 9 mechanisms of each patient. The study observed an increase in post-treatment mRNA levels for longer surviving patients in 6 mechanisms. Further analysis displayed how the drug treatment uniquely altered each of the mechanisms based on the length of patient survival. These results indicate that the PDE-based procedures described herein may provide a novel tool for discovering potential anti-breast cancer pharmaceuticals.



2021 ◽  
Author(s):  
Takaaki Matsuoka ◽  
Keita Takanashi ◽  
Katsuaki Dan ◽  
Kenichi Yamamoto ◽  
Koji Tomobe ◽  
...  

Abstract Background: The mechanism by which reactive oxygen species (ROS) produced by oxidative stress promote cellular senescence has been studied in detail. This study aimed to verify the preventive or therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-Ex) on the production of ROS induced by oxidative stress in human skin fibroblasts and clarify the mechanisms that promote cellular senescence.Methods: In a system where H2O2 was applied to skin fibroblasts, we assessed the effects of the application of MSC-Ex before and after oxidative stress and measured the fluctuations in several signaling molecules involved in subsequent intracellular stress responses. Exosomes were isolated from MSCs (MSC-Ex) and normal human dermal fibroblasts (NHDFs, NHDF-Ex) before and after exposure to H2O2. NHDFs were treated with exosomes before and after exposure to H2O2.Results: mRNA expression (aquaporin-1 and aquaporin-3) and hyaluronan secretion associated with skin moisturization were reduced by H2O2 treatment, whereas MSC-Ex reversed these effects. The cellular senescence induced by H2O2 was also reproduced in fibroblasts. Specifically, the downregulation of SIRT1 led to increased acetylated p53 expression over time, which induced the expression of p21, a downstream molecule of p53, and arrested the cell cycle, leading to cell senescence. MSC-Ex enhanced these signal transduction systems. MSC-Ex was also effective at blocking the increase of β-galactosidase activity and accumulation of ROS in cells. This effect was stronger than that of NHDF-Ex.Conclusion: MSC-Ex were found to act defensively against epidermal and cellular senescence induced by oxidative stress.



2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 515-515 ◽  
Author(s):  
Jin-Soo Kim ◽  
Sehhoon Park ◽  
Ki Hwan Kim ◽  
Jin Hyun Park ◽  
Won Kim ◽  
...  

515 Background: Oxaliplatin-based regimens are standard treatments for patients with colorectal (CRC) and advanced gastric cancer (AGC). However, the use of oxaliplatin sometimes results in hepatic sinusoidal obstruction syndrome (SOS). The aim of the study was to evaluate the utility of non-invasive liver fibrosis indices for monitoring oxaliplatin-induced hepatic SOS. We have reported a preliminary data in ASCO Annual Meeting 2014. Methods: From February 2004 to April 2014, patients with CRC or AGC who received oxaliplatin-based chemotherapy were studied. Possibility of SOS development was evaluated before and after the oxaliplatin exposure with splenic volume index (SVI). Four different non-invasive liver fibrosis indices were used for risk analysis: age-platelet index (API), AST to platelet ratio index (APRI), platelet to spleen ratio (PSR), Fibrosis-4 score (FIB-4). A prospective observation with serial elastrography is also ongoing. Results: A total of 275 patients were eligible for evaluation: 200 patients had CRC, and 75 patients had AGC. Using a cutoff of SVI increase ≥ 0.3, 113 patients (41.1%) were positive for hepatic SOS. Changes of indices were significantly correlated with SVI increase. Adjusted odds ratios for those indices were as follows: API = 1.16 (95% Confidential Interval [CI], 1.01 - 1.32; P = 0.032); APRI = 2.45 (95% CI, 1.30 - 4.63; P = 0.006); PSR = 0.69 (95% CI, 0.59 - 0.80; P < 0.001); FIB-4 = 1.37 (95% CI, 1.16 - 1.63; P < 0.001). Optimal cutoff-value with statistical significance were calculated and suggested. A total of 20 patients have been enrolled into the prospective observation until now. Comparison of elastographic changes and the indices in these patients will be presented. Conclusions: Changes of non-invasive liver fibrosis indices showed good correlation with SVI increase during oxaliplatin-based chemotherapy. These indices might be useful markers for monitoring of oxaliplatin-induced hepatic SOS. Serial monitoring of hepatic elastography could also be used for non-invasive monitoring of hepatic SOS.



2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A625-A625
Author(s):  
Chelsi L Flippo ◽  
Christina Tatsi ◽  
Ninet Sinaii ◽  
Maria de la Luz Sierra ◽  
Elena Belyavskaya ◽  
...  

Abstract Objectives: Chronic hypercortisolemia suppresses AVP secretion. Copeptin makes up the C-terminal portion of the AVP precursor pre-pro-AVP, is released in stoichiometric amounts with AVP, and is a stable surrogate marker of AVP.A post-operative increase in plasma copeptin was hypothesized to be a marker of remission of Cushing Disease (CD). Methods: Plasma copeptin was obtained in patients with CD before and daily in the first week after transsphenoidal surgery (TSS), measured using the Brahm Kryptor Compact PLUS sandwich immunofluorescent assay. Urine output, serum sodium, urine specific gravity, and urine/serum osmolality were used to determine development of central diabetes insipidus (DI) and/or syndrome of inappropriate anti-diuretic hormone secretion (SIADH). Change in copeptin reflects pre-TSS to peak post-TSS copeptin levels. Statistical analyses were completed using non-parametric tests. Results are presented as median (inter-quartile range). Results: Forty-four patients (64% female, 7-55 years old) were included. After TSS, 8 (18%) developed DI, 13 (30%) developed SIADH, 4 (9%) developed both DI and SIADH, and 19 (43%) developed neither. Thirty-three patients had a follow-up at 3-6 months. Overall, there was no difference in peak post-TSS copeptin for patients in remission versus those not in remission [6.1 pmol/L (4.3-12.1) vs. 7.3 pmol/L (5.4-8.4), p=0.88]. There was, also, no difference in the copeptin change for those in remission versus not in remission [2.3 pmol/L (-0.5-8.2) vs. 0.1 pmol/L (-0.1-2.2), p=0.46]. When we excluded patients who developed a water balance disorder postoperatively, there was a difference in peak post-TSS copeptin for those in remission [10.2 pmol/L (6.9-21.0)] vs. those not in remission [5.4 pmol/L (4.6-7.3), p=0.032], but not in the change in copeptin for those in remission vs. not in remission [5.1 pmol/L (0.3-19.5) vs. 1.1 pmol/L (-0.1-2.2), p=0.39]. Conclusions: Post-TSS plasma copeptin may be a useful early marker to predict remission of CD after TSS. However, the utility of this test may be limited to those who do not develop water balance disorders post-operatively. Additional studies with larger sample sizes are needed to confirm these findings and to determine a post-operative plasma copeptin cutoff level that may predict remission of CD.



2020 ◽  
Vol 18 (3) ◽  
pp. 417-423
Author(s):  
Nguyen Duy Anh ◽  
Nguyen Thi Sim ◽  
Phan Huyen Thuong ◽  
Tran Thi Phuong Thao ◽  
Hoang Van Tong ◽  
...  

Twin-twin transfusion syndrome (TTTS) is an unusual and serious condition that occurs in twin pregnancies when identical twins share a placenta but develop discordant amniotic fluid volumes. The TTTS has a high risk of fetal death and birth defects if left untreated. IL-1β, IL-6 and IL-8 have been shown to play an important role in preterm birth in twin pregnancies, which is one of the consequences of TTTS. This study quantified plasma levels of IL-1β, IL-6 and IL-8 in twin pregnant women with (n = 52) and without TTTS (n = 73) by ELISA and analyzed the association of interleukin expression levels with TTTS. The results showed that plasma concentrations of IL-1β and IL-8 were low and not significantly different between the first trimester and the second trimester of pregnancy, between the patients with and without TTTS or between patients with TTTS before and after treatment. IL-6 levels showed no significant difference between first trimester and second trimester of pregnancy or between patients with and without TTTS. Importantly, IL-6 levels were significantly elevated in TTTS patients after surgical treatment compared to those before surgical treatment. In conclusion, IL-6 may be considered as a potential marker for the prognosis of surgical treatment of TTTS.



Author(s):  
J. Temple Black

Tool materials used in ultramicrotomy are glass, developed by Latta and Hartmann (1) and diamond, introduced by Fernandez-Moran (2). While diamonds produce more good sections per knife edge than glass, they are expensive; require careful mounting and handling; and are time consuming to clean before and after usage, purchase from vendors (3-6 months waiting time), and regrind. Glass offers an easily accessible, inexpensive material ($0.04 per knife) with very high compressive strength (3) that can be employed in microtomy of metals (4) as well as biological materials. When the orthogonal machining process is being studied, glass offers additional advantages. Sections of metal or plastic can be dried down on the rake face, coated with Au-Pd, and examined directly in the SEM with no additional handling (5). Figure 1 shows aluminum chips microtomed with a 75° glass knife at a cutting speed of 1 mm/sec with a depth of cut of 1000 Å lying on the rake face of the knife.



Author(s):  
R. F. Bils ◽  
W. F. Diller ◽  
F. Huth

Phosgene still plays an important role as a toxic substance in the chemical industry. Thiess (1968) recently reported observations on numerous cases of phosgene poisoning. A serious difficulty in the clinical handling of phosgene poisoning cases is a relatively long latent period, up to 12 hours, with no obvious signs of severity. At about 12 hours heavy lung edema appears suddenly, however changes can be seen in routine X-rays taken after only a few hours' exposure (Diller et al., 1969). This study was undertaken to correlate these early changes seen by the roengenologist with morphological alterations in the lungs seen in the'light and electron microscopes.Forty-two adult male and female Beagle dogs were selected for these exposure experiments. Treated animals were exposed to 94.5-107-5 ppm phosgene for 10 min. in a 15 m3 chamber. Roentgenograms were made of the thorax of each animal before and after exposure, up to 24 hrs.



Author(s):  
M. H. Wheeler ◽  
W. J. Tolmsoff ◽  
A. A. Bell

(+)-Scytalone [3,4-dihydro-3,6,8-trihydroxy-l-(2Hj-naphthalenone] and 1,8-di- hydroxynaphthalene (DHN) have been proposed as intermediates of melanin synthesis in the fungi Verticillium dahliae (1, 2, 3, 4) and Thielaviopsis basicola (4, 5). Scytalone is enzymatically dehydrated by V. dahliae to 1,3,8-trihydroxynaphthalene which is then reduced to (-)-vermelone [(-)-3,4- dihydro-3,8-dihydroxy-1(2H)-naphthalenone]. Vermelone is subsequently dehydrated to DHN which is enzymatically polymerized to melanin.Melanin formation in Curvularia sp., Alternaria sp., and Drechslera soro- kiniana was examined by light and electron-transmission microscopy. Wild-type isolates of each fungus were compared with albino mutants before and after treatment with 1 mM scytalone or 0.1 mM DHN in 50 mM potassium phosphate buffer, pH 7.0. Both chemicals were converted to dark pigments in the walls of hyphae and conidia of the albino mutants. The darkened cells were similar in appearance to corresponding cells of the wild types under the light microscope.



Author(s):  
T. Gulik-Krzywicki ◽  
M.J. Costello

Freeze-etching electron microscopy is currently one of the best methods for studying molecular organization of biological materials. Its application, however, is still limited by our imprecise knowledge about the perturbations of the original organization which may occur during quenching and fracturing of the samples and during the replication of fractured surfaces. Although it is well known that the preservation of the molecular organization of biological materials is critically dependent on the rate of freezing of the samples, little information is presently available concerning the nature and the extent of freezing-rate dependent perturbations of the original organizations. In order to obtain this information, we have developed a method based on the comparison of x-ray diffraction patterns of samples before and after freezing, prior to fracturing and replication.Our experimental set-up is shown in Fig. 1. The sample to be quenched is placed on its holder which is then mounted on a small metal holder (O) fixed on a glass capillary (p), whose position is controlled by a micromanipulator.



Author(s):  
R. M. Anderson

Aluminum-copper-silicon thin films have been considered as an interconnection metallurgy for integrated circuit applications. Various schemes have been proposed to incorporate small percent-ages of silicon into films that typically contain two to five percent copper. We undertook a study of the total effect of silicon on the aluminum copper film as revealed by transmission electron microscopy, scanning electron microscopy, x-ray diffraction and ion microprobe techniques as a function of the various deposition methods.X-ray investigations noted a change in solid solution concentration as a function of Si content before and after heat-treatment. The amount of solid solution in the Al increased with heat-treatment for films with ≥2% silicon and decreased for films <2% silicon.



Sign in / Sign up

Export Citation Format

Share Document