scholarly journals Distinct nitrogen isotopic compositions of healthy and cancerous tissue in mice brain and head&neck micro-biopsies

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
M. Straub ◽  
D. M. Sigman ◽  
A. Auderset ◽  
J. Ollivier ◽  
B. Petit ◽  
...  

Abstract Background Cancerous cells can recycle metabolic ammonium for their growth. As this ammonium has a low nitrogen isotope ratio (15N/14N), its recycling may cause cancer tissue to have lower 15N/14N than surrounding healthy tissue. We investigated whether, within a given tissue type in individual mice, tumoral and healthy tissues could be distinguished based on their 15N/14N. Methods Micro-biopsies of murine tumors and adjacent tissues were analyzed for 15N/14N using novel high-sensitivity methods. Isotopic analysis was pursued in Nude and C57BL/6 mice models with mature orthotopic brain and head&neck tumors generated by implantation of H454 and MEERL95 murine cells, respectively. Results In the 7 mice analyzed, the brain tumors had distinctly lower 15N/14N than healthy neural tissue. In the 5 mice with head&neck tumors, the difference was smaller and more variable. This was at least partly due to infiltration of healthy head&neck tissue by tumor cells. However, it may also indicate that the 15N/14N difference between tumoral and healthy tissue depends on the nitrogen metabolism of the healthy organ in question. Conclusions The findings, coupled with the high sensitivity of the 15N/14N measurement method used here, suggest a new approach for micro-biopsy-based diagnosis of malignancy as well as an avenue for investigation of cancer metabolism.

2021 ◽  
Vol 60 (1) ◽  
pp. 223-236
Author(s):  
Walaa Maamoun ◽  
Mohamed I. Badawi ◽  
Ayman A Aly ◽  
Y. Khedr

Abstract Hyperthermia therapy is a promising therapy for liver cancer treatment that utilizes external electromagnetic waves to heat the tumor zone to preferentially kill or minimize cancer cells. Nevertheless, it’s a challenge to realize localized heating of the cancer tissue without harming the surrounding healthy tissue. This research proposes to utilize nanoparticles as microwave absorbers to enhance microwave imaging and achieve localized hyperthermia therapy. A realistic 3D abdomen model has been segmented using 3D Slicer segmentation software, and then the obtained segmented CAD model exported to Computer Simulation Technology (CST STUDIO) for applying the Finite Element Modeling (FEM). Next investigating both imaging and treatment capability. Finally, the specific absorption rate (SAR) and temperature distribution were computed without nanoparticles and with different types of nanoparticles such as gold (GNPs) and silver nanoparticles at frequency 915 MHz. By comparing the achived results, it was seen that Silver nanoparticles can make a great enhancement in raising the temperature. However, this result was unsatisfactory but, after adding gold nanoparticles the temperature exceed 42°C, at frequency 915 MHz which is achieving the hyperthermia treatment without harming the nearby healthy tissue, GNPs also can achieve a great enhancement in SAR result


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 675-675
Author(s):  
Meghan Graber ◽  
Hayley Barta

Abstract Diacylglycerol O-acyltransferase 2 is a transmembrane protein encoded by the DGAT2 gene that functions in lipid metabolism, triacylglycerol synthesis, and lipid droplet regulation. Since cancer cells exhibit altered lipid metabolism, it has been proposed that mutations in DGAT2 may contribute to this state. Using data from the Catalogue of Somatic Mutations in Cancer (COSMIC), we analyzed all reported DGAT2 mutations in human cancers. Bioinformatics analyses were performed to highlight the connections between age, pathogenicity, and cancer tissue type. Mutations are generally associated with samples from older individuals, except for those in glioblastomas which occur earlier. We also found that several DGAT2 mutations fall within the catalytic site of the enzyme and may affect enzyme function. Thus, these mutations may contribute to altered cancer metabolism. We identified D222V as a mutation hotspot neighboring a previously discovered Y223H mutation that causes Axonal Charcot-Marie-Tooth disease. Remarkably, Y223H has not been detected in cancers indicating it is inhibitory to cancer progression. Further analysis showed that most mutations do not affect DGAT2 gene expression suggesting this change is not a major contributor to cancer development. Intriguingly, although most cancers are characterized by low DGAT2 gene expression, some show high expression levels, indicating that, at least in certain cases, over-expression is not inhibitory to cellular proliferation. This work uncovers unknown roles of DGAT2 in cancers and suggests that its function may be more complex than previously appreciated.


2021 ◽  
Vol 7 (3) ◽  
pp. 51
Author(s):  
Emanuela Paladini ◽  
Edoardo Vantaggiato ◽  
Fares Bougourzi ◽  
Cosimo Distante ◽  
Abdenour Hadid ◽  
...  

In recent years, automatic tissue phenotyping has attracted increasing interest in the Digital Pathology (DP) field. For Colorectal Cancer (CRC), tissue phenotyping can diagnose the cancer and differentiate between different cancer grades. The development of Whole Slide Images (WSIs) has provided the required data for creating automatic tissue phenotyping systems. In this paper, we study different hand-crafted feature-based and deep learning methods using two popular multi-classes CRC-tissue-type databases: Kather-CRC-2016 and CRC-TP. For the hand-crafted features, we use two texture descriptors (LPQ and BSIF) and their combination. In addition, two classifiers are used (SVM and NN) to classify the texture features into distinct CRC tissue types. For the deep learning methods, we evaluate four Convolutional Neural Network (CNN) architectures (ResNet-101, ResNeXt-50, Inception-v3, and DenseNet-161). Moreover, we propose two Ensemble CNN approaches: Mean-Ensemble-CNN and NN-Ensemble-CNN. The experimental results show that the proposed approaches outperformed the hand-crafted feature-based methods, CNN architectures and the state-of-the-art methods in both databases.


2021 ◽  
pp. 112067212199663
Author(s):  
Kemal Turgay Özbilen ◽  
Tuncay Gündüz ◽  
Selva Nur Çukurova Kartal ◽  
Ali Ceyhun Gedik ◽  
Mefküre Eraksoy ◽  
...  

Purpose: Bruch’s membrane opening-minimum rim width (BMO-MRW) and RNFL measured using anatomic positioning system (APS-RNFL) are novel OCT methods and remained unexplored in MS patients. To investigate the novel parameters of spectral-domain OCT as an alternative biomarker in patients with multiple sclerosis (MS). Methods: Retrospective cohort study; participants consisted of relapsing-remitting MS (RRMS) patients and healthy controls (HC). Eyes were classified according to the presence of MS and previous optic neuritis (ON). Measurements of standard peripapillary RNFL (S-RNFL), BMO-MRW, and APS-RNFL were performed. Result: A total of 244 eyes of 122 participants (MS-patients: 63, HC: 59) were included in the study. Fifty-one eyes had a history of previous ON. In almost all measured parameters, neuroretinal rim thicknesses were observed the thinnest in eyes with ON history between all subgroups. S-RNFL and APS-RNFL techniques showed the difference in neuroretinal rim thickness in all three subjects (ON+, ON−, and HC). However, BMO-MRW, on the other hand, could not distinguish between ON(−) patients and HC. The relationship between OCT parameters and EDSS were observed only in eyes with an ON history in all three techniques. A meaningful model with 78% accuracy was obtained by using only the OCT parameters as risk factors. In the ROC analysis, no parameters were found to have acceptable high sensitivity and specificity. BMO-MRW was statistically weaker in every aspect than other RNFL techniques. Conclusion: The novel APS-RNFL technique appears to be a bit more reliable alternative to S-RNFL technique to support therapeutic decision-making in MS. BMO-MRW has not been found as a successful alternative to S-RNFL.


2021 ◽  
Author(s):  
Feng Gao ◽  
Xiaolong Tu ◽  
Yongfang Yu ◽  
Yansha Gao ◽  
Jin Zou ◽  
...  

Abstract Herein, an efficient electrochemical sensing platform is proposed for selective and sensitive detection of nitrite on the basis of Cu@C@Zeolitic imidazolate framework-8 (Cu@C@ZIF-8) heterostructure. Core-shell Cu@C@ZIF-8 composite was synthesized by pyrolysis of Cu-metal-organic framework@ZIF-8 (Cu-MOF@ZIF-8) in Ar atmosphere on account of the difference of thermal stability between Cu-MOF and ZIF-8. For the sensing system of Cu@C@ZIF-8, ZIF-8 with proper pore size allows nitrite diffuse through the shell, while big molecules cannot, which ensures high selectivity of the sensor. On the other hand, Cu@C as electrocatalyst promotes the oxidation of nitrite, thereby resulting high sensitivity of the sensor. Accordingly, the Cu@C@ZIF-8 based sensor presents excellent performance for nitrite detection, which achieves a wide linear response range of 0.1 µM to 300.0 µM, and a low limit of detection (LOD) of 0.033 µM. In addition, the Cu@C@ZIF-8 sensor possesses excellent stability and reproducibility, and was employed to quantify nitrite in sausage samples with recoveries of 95.45-104.80%.


1988 ◽  
Vol 136 (1) ◽  
pp. 351-361
Author(s):  
LEONA MATTSOFF ◽  
MIKKO NIKINMAA

We studied the effects of acute external acidification on the acid-base status and plasma and red cell ion concentrations of lampreys. Mortality was observed within 24 h at pH5 and especially at pH4. The main reason for the high sensitivity of lampreys to acid water appears to be the large drop in blood pH: 0.6 and 0.8 units after 24 h at pH5 and pH4, respectively. The drop of plasma pH is much larger than in teleost fishes exposed to similar pH values. The difference in the plasma pH response between lampreys and teleosts probably results from the low buffering capacity of lamprey blood, since red cells cannot participate in buffering extracellular acid loads. Acidification also caused a decrease in both Na+ and C− concentrations and an elevation in K+ concentration of plasma. The drop in plasma Na+ concentration occurred faster than the drop in plasma Cl− concentration which, in turn, coincided with the decrease in total CO2 concentration of the blood.


2021 ◽  
Vol 8 (12) ◽  
pp. 1799
Author(s):  
Momammed Mustafizur Rahman ◽  
Shabnam Imam ◽  
Sayedatun Nessa ◽  
A. K. M. Maruf Raza ◽  
Farida Arjuman ◽  
...  

Background: This cross- sectional observational study was carried out with an aim to look for microsatellite instability (MSI) status in colorectal carcinoma and their association with different histomorphological patterns and biological behavior of colorectal carcinoma.Methods: This cross-sectional observational study was done in the Department of Pathology, Bangabandhu Sheikh Mujib Medical University Hospital (BSMMU), Dhaka, Bangladesh during September 2014 to October 2015. A total of 39 surgically resected sample of colorectal carcinoma were included. Consent from each patient was taken. The samples were histopathologically evaluated according to the standard protocol. The statistical analyses were done using Statistical packages for social sciences (SPSS 15) for Windows.Results: A total of 39 cases of colorectal carcinoma were included in this study. Majority of the patients (55.5%) was in 6th decade in MSI and 29.1% were MSI absent group. The mean age was found 47.67±10.97 years in present group and 47.84±14.26 years in absent group. The difference was not statistically significant (p>0.05). TNM stage with MSI was observed. The mean CEA level was 100.74±103.66 and 60.43±91.72. The mean Hb was 9.72±1.99 % and 9.92±2.17, the range was 7.2-12.2 and 4.6-13.4 among the groups. The mean difference was not statistically significant (p>0.05). Ulcerated was 3 (33.3%) and 19 (64.5%). Stage 3 tumor was 4 (44.4%) and 16 (51.6%). Grade 2 tumor was 5 (55.6%) and 17 (58.0%).Conclusions: For the first time in Bangladesh, this study was undertaken to evaluate the microsatellite instability (MSI) status in colorectal cancer tissue and their association with different histomorphological patterns of colorectal carcinoma.   


2004 ◽  
Vol 50 (8) ◽  
pp. 1356-1363 ◽  
Author(s):  
Nicolai Grebenchtchikov ◽  
Arend Brinkman ◽  
Simone P J van Broekhoven ◽  
Danielle de Jong ◽  
Anneke Geurts-Moespot ◽  
...  

Abstract Background: High concentrations of breast cancer anti-estrogen resistance 1 (BCAR1) protein measured by Western blotting in primary breast tumor cytosols are associated with early disease progression and failure of tamoxifen therapy. The aim of the present study was to develop an ELISA to measure BCAR1 quantitatively in extracts of human breast cancer tissue. Methods: A recombinant fragment of BCAR1 (the human homolog of murine p130Cas) was produced in bacterial M15 cells, purified, and injected into chickens and rabbits. The generated antibodies were affinity-purified and used for the construction of an ELISA. After validation, the results obtained with the ELISA were compared with Western blot findings on primary breast tumors. Results: The detection limit the BCAR1 ELISA was 0.0031 μg/L, and the within-run imprecision (CV) was <20% at concentrations down to 0.004 μg/L. The within-run imprecision (CV) was 1.0–7.2%, and the between-run CV was 3.6–5.4%. There was no cross-reactivity with family member HEF1. The assay exhibited parallelism of results between serial dilutions and a mean recovery (range) of 96 (79–118)%. Conclusions: The ELISA measures BCAR1 in human breast cancer cytosols with high sensitivity and specificity. The assay can be used to confirm and to quantitatively extend previous semiquantitative Western blot data on the prognostic and predictive value of BCAR1 in human breast cancer; it can also be applied for other diseases.


In a previous paper it was shown that 0·0007 per cent, of 29 Cu and 0·0003 per cent, of 26 Fe could be detected in 30 Zn by atomic analysis by X-ray spectroscopy. This sensitivity is greater than that which was claimed by Noddack, Tacke, and Berg, who set the limit at about 0·1 per cent, for non-metals, and by Hevesy, who stated it to be about 0·01 per cent, for an element present in an alloy. It was later suggested by Hevesy that the high value of the sensitivity which we found might result from the fact that some of the alloys we had used were composed of elements of almost equal atomic number, and that the sensitivity would be smaller for a constituent of low atomic number mixed with a major constituent of high atomic number. To elucidate these disagreements we have made further observations of the sensitivity with elements of different atomic number and have investigated the conditions which can influence the sensitivity. The Factors Determining Sensitivity . The detection of one element in a mixture of elements depends upon the identification of its K or L lines in the general spectrum emitted by the mixture under examination. The intensity with which these lines are excited in the target (“excited intensity”) is proportional to the number of atoms of the constituent element excited, i. e ., to its concentration and to the volume of the target in which the cathode ray energy is absorbed. The depth of penetration of the cathode rays is determined by the density of the target material and by their velocity ( i. e ., by the voltage applied to the X-ray tube). Schonland has shown that the range of homogeneous cathode rays in different elements, expressed as a mass per unit area, is approximately constant and is independent of the atomic number of the absorbing element. When their velocity is increased, the cathode rays will penetrate to a greater depth, and therefore a greater number of atoms of all constituents will be ionised. This will increase the “excited intensity” of the lines due to the particular constituent sought equally with those lines of the other elements present. The intensity of a line further depends upon the difference between the voltage applied to the X-ray tube and that necessary to excite the series. For these reasons, a high applied voltage is required for a high sensitivity.


2020 ◽  
Vol 4 ◽  
pp. 65-71
Author(s):  
E.A. Veshkin ◽  
◽  
V.I. Postnov ◽  
V.V. Semenychev ◽  
E.V. Krasheninnikova ◽  
...  

The change in the microhardness over the thickness of samples made of EDT-69N binder cured in vacuum and at atmospheric pressure at temperatures from 130 to 170°C was investigated. It was found that the change in microhardness along the thickness of the samples occurs according to the parabolic law, with the maximum values being achieved in the middle of the sample cross-section along the thickness. With an increase in the molding temperature, the microhardness in the middle section of the sample increases from 222 MPa at a molding temperature of 130°C to 410 MPa during molding at 170°C. At the critical molding temperature (170°C), the microhardness in all zones of the specimen cross section (subsurface, semi-average, and core) levels off, while the parabolic dependence degenerates into a straight line. It is shown that the method of scratching (sclerometry) demonstrated a sufficiently high sensitivity to the state of samples cured at different temperatures. With an increase in the molding temperature, the width of the sclerometric grooves decreases. At a critical molding temperature of 170°C, the groove width is stabilized and becomes constant throughout the sample thickness. To characterize the difference in the values of the microhardness of the cured binder in the sample volume, it is proposed to use a dimensionless “coefficient of volume anisotropy,” which can take a positive, negative or zero value. With an increase in the curing temperature of the binder and, accordingly, with an increase in the microhardness of the sample, the coefficient of volume anisotropy decreases, and when the samples are molded at the critical temperature, it turns to zero, which indicates the absence of anisotropy.


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