scholarly journals In-Cell Determination of Lactate Dehydrogenase Activity in a Luminal Breast Cancer Model – ex vivo Investigation of Excised Xenograft Tumor Slices Using dDNP Hyperpolarized [1-13C]pyruvate

Sensors ◽  
2019 ◽  
Vol 19 (9) ◽  
pp. 2089 ◽  
Author(s):  
Yael Adler-Levy ◽  
Atara Nardi-Schreiber ◽  
Talia Harris ◽  
David Shaul ◽  
Sivaranjan Uppala ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lactate Dehydrogenase ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Lactate Production ◽  
Response Assessment ◽  
Luminal Breast Cancer ◽  
Cancer Type ◽  
Lactate Dehydrogenase Activity ◽  
Ldh Activity

[1-13C]pyruvate, the most widely used compound in dissolution-dynamic nuclear polarization (dDNP) magnetic resonance (MR), enables the visualization of lactate dehydrogenase (LDH) activity. This activity had been demonstrated in a wide variety of cancer models, ranging from cultured cells, to xenograft models, to human tumors in situ. Here we quantified the LDH activity in precision cut tumor slices (PCTS) of breast cancer xenografts. The Michigan Cancer Foundation-7 (MCF7) cell-line was chosen as a model for the luminal breast cancer type which is hormone responsive and is highly prevalent. The LDH activity, which was manifested as [1-13C]lactate production in the tumor slices, ranged between 3.8 and 6.1 nmole/nmole adenosine tri-phosphate (ATP) in 1 min (average 4.6 ± 1.0) on three different experimental set-ups consisting of arrested vs. continuous perfusion and non-selective and selective RF pulsation schemes and combinations thereof. This rate was converted to an expected LDH activity in a mass ranging between 3.3 and 5.2 µmole/g in 1 min, using the ATP level of these tumors. This indicated the likely utility of this approach in clinical dDNP of the human breast and may be useful as guidance for treatment response assessment in a large number of tumor types and therapies ex vivo.

scholarly journals Lactate dehydrogenase activity staining demonstrates time-dependent immune cell infiltration in human ex-vivo burn-injured skin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joshua Cuddihy ◽  
Gongjie Wu ◽  
Laptin Ho ◽  
Hiromi Kudo ◽  
Andreas Dannhorn ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Immune Cell ◽  
Burn Injury ◽  
Ex Vivo ◽  
Cell Types ◽  
Steady Increase ◽  
Cellular Infiltration ◽  
Lactate Dehydrogenase Activity ◽  
Burn Wounds ◽  
Ldh Activity

AbstractBurn injuries constitute one of the most serious accidental injuries. Increased metabolic rate is a hallmark feature of burn injury. Visualising lactate dehydrogenase (LDH) activity has been previously used to identify metabolic activity differences, hence cell viability and burn depth in burn skin. LDH activity was visualised in injured and uninjured skin from 38 sub-acute burn patients. LDH activity aided the identification of spatially correlating immunocompetent cells in a sub-group of six patients. Desorption Electrospray Ionisation Mass Spectrometry Imaging (DESI MSI) was used to describe relative lactate and pyruvate abundance in burned and uninjured tissue. LDH activity was significantly increased in the middle and deep regions of burnt skin compared with superficial areas in burnt skin and uninjured tissue and positively correlated with post-burn time. Regions of increased LDH activity showed high pyruvate and low lactate abundance when examined with DESI-MSI. Areas of increased LDH activity exhibited cellular infiltration, including CD3 + and CD4 + T-lymphocytes and CD68 + macrophages. Our data demonstrate a steady increase in functional LDH activity in sub-acute burn wounds linked to cellular infiltration. The cell types associated are related to tissue restructuring and inflammation. This region in burn wounds is likely the focus of dysregulated inflammation and hypermetabolism.

scholarly journals MODELING THE EFFECTS OF LEAD POLLUTION ON LACTATE DEHYDROGENASE ACTIVITY

10.23856/3305 ◽  
2019 ◽  
Vol 33 (2) ◽  
pp. 50-55
Author(s):  
Olena Konovalova
Keyword(s):  
Heavy Metals ◽  
Lactate Dehydrogenase ◽  
Energy Metabolism ◽  
Lead Acetate ◽  
Lead Pollution ◽  
Lactate Dehydrogenase Activity ◽  
Influence Mechanism ◽  
Ldh Activity ◽  
Small Doses ◽  
Experimental Substantiation

The changes of activity of LDH and its isoenzymatic fractions under load with lead acetate are described. The introduction of a subacute dose of Pb2 + led to a decrease in the LDH activity of the rat liver and an increase in the heart. Preliminary introduction of small doses of Pb2 + partially prevents increased LDH activity in the heart and completely inhibits its increase in the liver. The proportion of urea-stable fraction in the heart and blood serum is significantly increased, indicating an increase in the aerobic direction of energy metabolism. The obtained results are the experimental substantiation of further investigations of influence mechanism of heavy metals on the organism, as well as the motivation to prevent environmental pollution by man-made xenobiotics.

scholarly journals Urinary Lactate Dehydrogenase Activity and Its Isozyme Patterns in Kawasaki Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
Yoichi Kawamura ◽  
Seiichiro Takeshita ◽  
Takashi Kanai ◽  
Mari Takizawa ◽  
Yusuke Yoshida ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Kawasaki Disease ◽  
Pattern Analysis ◽  
Upper Urinary Tract ◽  
Potential Significance ◽  
Lactate Dehydrogenase Activity ◽  
Isozyme Patterns ◽  
Ldh Activity ◽  
Sterile Pyuria ◽  
Ldh Isozymes

Abnormal urinary findings, such as sterile pyuria, proteinuria, and microscopic hematuria, are often seen in the acute phase of Kawasaki disease (KD). We investigated the potential significance of urinary lactate dehydrogenase (U-LDH) activity and its isozyme patterns in KD. Total U-LDH activity and its isozymes (U-LDH1-5) levels were compared among 120 patients with KD, 18 patients with viral infection (VI), and 43 patients with upper urinary tract infection (UTI) and additionally compared between intravenous immunoglobulin (IVIG) responders (n=89) and nonresponders (n=31) with KD. Total U-LDH activity was higher in KD (35.4±4.8 IU/L, P<0.05) and UTI patients (66.0±8.0 IU/L, P<0.01) than in VI patients (17.0±6.2 IU/L). In the isozyme pattern analysis, KD patients had high levels of U-LDH1 and U-LDH2, while UTI patients had high levels of U-LDH3, U-LDH4, and U-LDH5. Furthermore, IVIG nonresponders of KD had significantly higher levels of total U-LDH activity (45.1±4.7 IU/L, P<0.05), especially U-LDH1 and U-LDH2 (P<0.05), than IVIG responders (32.0±2.8 IU/L). KD patients have increased levels of total U-LDH activity, especially U-LDH-1 and U-LDH2, indicating a unique pattern of U-LDH isozymes different from that in UTI patients.

Lactate Dehydrogenase Activity and Isoenzyme Patterns in Serous Middle Ear Effusions

1973 ◽  
Vol 82 (2) ◽  
pp. 192-195 ◽  
Author(s):  
S. K. Juhn ◽  
John S. Huff ◽  
Michael M. Paparella
Keyword(s):  
Lactate Dehydrogenase ◽  
Otitis Media ◽  
Middle Ear ◽  
Biochemical Characterization ◽  
Middle Ear Mucosa ◽  
Lactate Dehydrogenase Activity ◽  
Intracellular Enzyme ◽  
Ldh Activity ◽  
Serous Otitis Media ◽  
Isoenzyme Patterns

Biochemical characteristics of middle ear effusions (MEE) should provide a better understanding of the etiopathogenesis of serous otitis media. In order to develop another parameter for the biochemical characterization of the MEE, lactate dehydrogenase (LDH) and LDH isoenzyme patterns in the serous middle ear effusion and serum from 20 patients with serous otitis media were compared. The LDH activity was measured by the usual spectrophotometric method. The isoenzyme patterns were compared on electropherograms using cellulose polyacetate strips. The LDH activity in MEE was significantly higher (P < 0.001) than it was in serum. Fractions of isoenzymes 1 and 2 were each smaller in MEE than in serum. Isoenzymes 4 and 5 have a significantly higher (P < 0.001) fraction in MEE than in serum. Since LDH is an intracellular enzyme and middle ear mucosa is reported to have high content of isoenzymes 4 and 5, the inflammatory changes in the middle ear mucosa which may release intracellular LDH, are suggested as the cause of both higher activity of LDH and the higher fractions of isoenzymes 4 and 5 in MEE than those in the serum.

Myristica fragrans Suppresses Tumor Growth and Metabolism by Inhibiting Lactate Dehydrogenase A

2016 ◽  
Vol 44 (05) ◽  
pp. 1063-1079 ◽  
Author(s):  
Eun-Yeong Kim ◽  
Hee-Jung Choi ◽  
Mi-Ju Park ◽  
Yeon-Seop Jung ◽  
Syng-Ook Lee ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Lactate Production ◽  
High Rate ◽  
Potential Candidate ◽  
Ldh Activity ◽  
Myristica Fragrans

Most cancer cells predominantly produce ATP by maintaining a high rate of lactate fermentation, rather than by maintaining a comparatively low rate of tricarboxylic acid cycle, i.e., Warburg’s effect. In the pathway, the pyruvate produced by glycolysis is converted to lactic acid by lactate dehydrogenase (LDH). Here, we demonstrated that water extracts from the seeds of Myristica fragrans Houtt. (MF) inhibit the in vitro enzymatic activity of LDH. MF effectively suppressed cell growth and the overall Warburg effect in HT29 human colon cancer cells. Although the expression of LDH-A was not changed by MF, both lactate production and LDH activity were decreased in MF-treated cells under both normoxic and hypoxic conditions. In addition, intracellular ATP levels were also decreased by MF treatment, and the uptake of glucose was also reduced by MF treatment. Furthermore, the experiment on tumor growth in the in vivo mice model revealed that MF effectively reduced the growth of allotransplanted Lewis lung carcinoma cells. Taken together, these results suggest that MF effectively inhibits cancer growth and metabolism by inhibiting the activity of LDH, a major enzyme responsible for regulating cancer metabolism. These results implicate MF as a potential candidate for development into a novel drug against cancer through inhibition of LDH activity.

scholarly journals Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pauliina M. Munne ◽  
Lahja Martikainen ◽  
Iiris Räty ◽  
Kia Bertula ◽  
Nonappa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Therapeutic Interventions ◽  
Preclinical Model ◽  
Matrix Stiffness ◽  
Breast Cancers ◽  
Ex Vivo Model ◽  
Major Barrier ◽  
The Matrix

AbstractBreast cancer is now globally the most frequent cancer and leading cause of women’s death. Two thirds of breast cancers express the luminal estrogen receptor-positive (ERα + ) phenotype that is initially responsive to antihormonal therapies, but drug resistance emerges. A major barrier to the understanding of the ERα-pathway biology and therapeutic discoveries is the restricted repertoire of luminal ERα + breast cancer models. The ERα + phenotype is not stable in cultured cells for reasons not fully understood. We examine 400 patient-derived breast epithelial and breast cancer explant cultures (PDECs) grown in various three-dimensional matrix scaffolds, finding that ERα is primarily regulated by the matrix stiffness. Matrix stiffness upregulates the ERα signaling via stress-mediated p38 activation and H3K27me3-mediated epigenetic regulation. The finding that the matrix stiffness is a central cue to the ERα phenotype reveals a mechanobiological component in breast tissue hormonal signaling and enables the development of novel therapeutic interventions. Subject terms: ER-positive (ER + ), breast cancer, ex vivo model, preclinical model, PDEC, stiffness, p38 SAPK.

Quantitative biochemical analysis of lactate dehydrogenase in human ovarian tissues: correlation with tumor grade

2005 ◽  
Vol 15 (3) ◽  
pp. 438-444 ◽  
Author(s):  
Š. ŠIMAGA ◽  
M. Osmak ◽  
D. Babič ◽  
M. ŠPREM ◽  
B. Vukelič ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Specific Activity ◽  
Malignant Tumors ◽  
Ovarian Tissue ◽  
Tumor Grade ◽  
Benign Tumors ◽  
Ovarian Carcinomas ◽  
Lactate Dehydrogenase Activity ◽  
Ldh Activity ◽  
Benign Ovarian Tumor

In an attempt to identify glycolytic capacity of normal and neoplastic human ovary, total lactate dehydrogenase (LDH) activity was measured in tissue cytosol originating from 69 patients (18 with benign ovarian tumor, 34 with ovarian carcinoma, six with nonepithelial ovarian malignant tumors, and 11 with tumor metastatic to ovary) and compared to the LDH activity of normal ovarian tissues (n = 19). Median value of total LDH-specific activity expressed as U/mg protein was 0.546 in normal tissues, 0.584 in benign tumors, 1.071 in malignancies metastatic to ovaries, 0.872 in nonepithelial primary ovarian tumors, and 0.818 in primary carcinomas. A significant rise in LDH-specific activity was found in malignant primary and secondary tumors of epithelial and nonepithelial origin, but not in benign neoplasms, compared to the activity in normal tissue. Ovarian carcinomas of serous histologic type did not differ in LDH activity from mucinous tumors. However, poorly differentiated carcinomas (grade 3) showed significantly enhanced activity of this glycolytic enzyme when compared to its grade 1 counterpart. The subgroup of grade 1 tumors did not differ in LDH activity from normal and benign ovarian tissue. Obtained results suggest that direct correlation might exist between ovarian epithelial tumor grade and lactate dehydrogenase activity.

scholarly journals Custodiol-MP for ex vivo lung perfusion – A comparison in a porcine model of donation after circulatory determination of death

2021 ◽  
pp. 039139882199066
Author(s):  
Katharina Kalka ◽  
Zoe Keldenich ◽  
Henning Carstens ◽  
Björn Walter ◽  
Ursula Rauen ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Functional Outcomes ◽  
Porcine Model ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
Determination Of Death ◽  
Ex Vivo Lung Perfusion ◽  
Lactate Dehydrogenase Activity ◽  
Lactate Levels

Introduction: Ex vivo lung perfusion (EVLP) is an established technique to evaluate and eventually recondition lungs prior to transplantation. Custodiol-MP (C-MP) solution is a new solution, designed for clinical machine perfusion, that has been used for kidneys. The aim of this study was to compare the effects of EVLP with Custodiol-MP on lung functional outcomes to the gold standard of EVLP with Steen Solution™. Material and Methods: In a porcine EVLP model of DCDD (Donation after Circulatory Determination of Death), lungs were perfused with Steen Solution™ (SS, n = 7) or Custodiol-MP solution supplemented with 55 g/l albumin (C-MP, n = 8). Lungs were stored cold for 4 h in low potassium dextran solution and subsequently perfused ex vivo for 4 h. During EVLP pulmonary gas exchange, activities of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) as well as levels of lactate in the perfusate were recorded hourly. Results: Oxygenation capacity differed significantly between groups (averaged over 4 h: SS 274 ± 178 mmHg; C-MP 284 ± 151 mmHg p = 0.025). Lactate dehydrogenase activities and lactate concentrations were significantly lower in Custodiol-MP perfused lungs. In a porcine model of DCDD with 4 h of EVLP the use of modified Custodiol-MP as perfusion solution was feasible. The use of C-MP showed at least comparable lung functional outcomes to the use of Steen SolutionTM. Furthermore C-MP perfusion resulted in significantly lower lactate dehydrogenase activity and lactate levels in the perfusate and higher oxygenation capacity.

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