scholarly journals Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 520 ◽  
Author(s):  
Tsukasa Yagi ◽  
Muhammad Shoaib ◽  
Cyrus Kuschner ◽  
Mitsuaki Nishikimi ◽  
Lance Becker ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Research ◽  
Lysophosphatidic Acid ◽  
Room Temperature ◽  
Storage Time ◽  
Ethylenediaminetetraacetic Acid ◽  
Future Studies ◽  
Blood Drawing ◽  
Benign Ovarian Tumors ◽  
Artificial Changes

Increased detection of plasma lysophosphatidic acid (LPA) has been proposed as a potential diagnostic biomarker in ovarian cancer, but inconsistency exists in these reports. It has been shown that LPA can undergo an artificial increase during sample processing and analysis, which has not been accounted for in ovarian cancer research. The aim of this study is to provide a potential explanation about how the artificial increase in LPA may have interfered with previous LPA analysis in ovarian cancer research. Using an established LC-MS method, we measured LPA and other lysophospholipid levels in plasma obtained from three cohorts of patients: non-cancer controls, patients with benign ovarian tumors, and those with ovarian cancer. We did not find the LPA level to be higher in cancer samples. To understand this inconsistency, we observed that LPA content changed more significantly than other lysophospholipids as a function of plasma storage time while frozen. Additionally, only LPA was found to be adversely impacted by incubation time depending on the Ethylenediaminetetraacetic acid (EDTA) concentration used during blood drawing. We also show that the inhibition of autotaxin effectively prevented artificial LPA generation during incubation at room temperature. Our data suggests that the artificial changes in LPA content may contribute to the discrepancies reported in literature. Any future studies planning to measure plasma LPA should carefully design the study protocol to consider these confounding factors.

Platelet Function in Ovarian Cancer

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4656-4656
Author(s):  
Shuju Feng ◽  
Michael H. Kroll ◽  
Alpa M. Nick ◽  
Anil Sood ◽  
Vahid Afshar-Kharghan
Keyword(s):  
Ovarian Cancer ◽  
Venous Thromboembolism ◽  
Platelet Aggregation ◽  
Cancer Patients ◽  
Room Temperature ◽  
Ovarian Tumors ◽  
Benign Tumors ◽  
Blood Samples ◽  
Benign Ovarian Tumors ◽  
Aggregation Of Platelets

Abstract A significant number of patients with ovarian cancer develop venous thromboembolism that is associated with a worse prognosis. The etiology of an increased frequency of venous thrombosis in cancer patients is not clear, and various hypotheses, including the presence of hyperreactive platelets, have been postulated. Hyperreactive platelets have a lower threshold for aggregation, and hence there is a higher number of degranulated platelets in circulation and a higher concentration of platelet granular contents in plasma. We compared ADP- and collagen-induced platelet aggregation in patients with ovarian cancer to those in patients with benign ovarian tumors. To reduce the effect of confounding factors such as surgery or chemotherapy, all blood samples were collected prior to any surgical interventions or chemotherapy. To detect hyperreactivity of platelets, we used both low and high doses of platelet agonists. To evaluate platelet preactivation at baseline, we measured the plasma concentration of b-thromboglobulin (b-TG) and platelet factor-4 (PF-4) as markers of platelet α granule secretion. All studies were approved by the Institutional Review Boards of the University of Texas, M.D. Anderson Cancer Center. Whole blood samples were collected from 34 patients with ovarian cancer and 19 patients with benign ovarian tumors into sodium citrate anticoagulant and processed within 2 hours after collection. Platelet rich plasma (PRP) was prepared by 15 min of 850 rpm centrifugation at room temperature. Aggregation studies were conducted in a light transmission aggregometer (Bio/Data Corporation), using ADP (at 2mM and 20 mM) and collagen (at 19 mg/ml and 190 mg/ml). Platelet poor plasma (PPP) was prepared by centrifuging PRP samples at 2500 rpm for 20 min at room temperature. All PPP samples were stored at -80ºC and the quantity of b-TG and PF-4 was determined by ELISA. We found that platelets isolated from ovarian cancer patients showed aggregation responses similar to platelets from patients with benign ovarian tumors (Figure 1). There was a statistically significant difference in the high-dose collagen-induced platelet aggregation between cancer and benign tumor samples, with increased aggregation of platelets from patients with benign tumors (79 ± 4.9%) in comparison to aggregation of platelets from cancer platelets (69 ± 6.3%). To investigate preactivation of platelets in cancer patients, we measured b-TG and PF-4 in PPP samples. We did not detect a higher concentration of b-TG and PF-4 in cancer PPP samples (Figure 2). In fact, PPP from cancer patients had a lower concentration of both α granule constituents. In the case of PF-4, the difference was statistically significant (9.8 ± 1.5 ng/ml for cancer patients versus 11.7 ± 1.7 ng/ml for patients with non-malignant tumors). We conclude that platelets from ovarian cancer patients are not hyperreactive and are not degranulated or preactivated. Links between ovarian cancer, venous thromboembolism and platelets may be absent or may involve non-hemostatic platelet functions. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells

Neoplasia ◽  
2015 ◽  
Vol 17 (9) ◽  
pp. 723-734 ◽  
Author(s):  
Abir Mukherjee ◽  
Yibao Ma ◽  
Fang Yuan ◽  
Yongling Gong ◽  
Zhenyu Fang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Lysophosphatidic Acid ◽  
Ovarian Cancer Cells ◽  
Hexokinase Ii

scholarly journals Discoidin Domain Receptor 2 Mediates Lysophosphatidic Acid-Induced Ovarian Cancer Aggressiveness

2021 ◽  
Vol 22 (10) ◽  
pp. 5374
Author(s):  
Bo Young Jeong ◽  
Kyung Hwa Cho ◽  
Se-Hee Yoon ◽  
Chang Gyo Park ◽  
Hwan-Woo Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cell ◽  
Lysophosphatidic Acid ◽  
Cell Invasion ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Invasion ◽  
Discoidin Domain Receptor ◽  
Cancer Aggressiveness ◽  
Discoidin Domain Receptor 2

Lysophosphatidic acid (LPA), a bioactive lipid produced extracellularly by autotaxin (ATX), has been known to induce various pathophysiological events, including cancer cell invasion and metastasis. Discoidin domain receptor 2 (DDR2) expression is upregulated in ovarian cancer tissues, and is closely associated with poor clinical outcomes in ovarian cancer patients. In the present study, we determined a critical role and signaling cascade for the expression of DDR2 in LPA-induced ovarian cancer cell invasion. We also found ectopic expression of ATX or stimulation of ovarian cancer cells with LPA-induced DDR2 expression. However, the silencing of DDR2 expression significantly inhibited ATX- and LPA-induced ovarian cancer cell invasion. In addition, treatment of the cells with pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), Akt, and mTOR abrogated LPA-induced DDR2 expression. Moreover, we observed that HIF-1α, located downstream of the mTOR, is implicated in LPA-induced DDR2 expression and ovarian cancer cell invasion. Finally, we provide evidence that LPA-induced HIF-1α expression mediates Twist1 expression to upregulate DDR2 expression. Collectively, the present study demonstrates that ATX, and thereby LPA, induces DDR2 expression through the activation of the PI3K/Akt/mTOR/HIF-1α/Twist1 signaling axes, aggravating ovarian cancer cell invasion.

Stem-like tumor cells and proinflammatory cytokines in the ascitic fluid of ovarian cancer patients

2021 ◽  
Vol 66 (5) ◽  
pp. 297-303
Author(s):  
S. O. Gening ◽  
T. V. Abakumova ◽  
I. I. Antoneeva ◽  
A. A. Rizvanov ◽  
T. P. Gening ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Blood Serum ◽  
Tumor Cells ◽  
Ascitic Fluid ◽  
Early Stage ◽  
Abdominal Cavity ◽  
Disease Stage ◽  
Cell Populations ◽  
Benign Ovarian Tumors ◽  
Number Of Cells

Ovarian cancer (OC) is able to develop implantation metastases in the abdominal cavity. Ascites is potentially useful for evaluating cancer features. The aim of the study was to assess the content of stem-like tumor cells and inflammatory mediators in ascites of OC. The prospective study included 11 patients with primary OC having ascites, 8 patients with benign ovarian tumors having ascites and 22 healthy women. In ascitic fluid obtained by laparocentesis, the populations of tumor stem-like cells were determined on a Cytoflex S` flow cytometer (Beckman Coulter, USA) and CytExpert Software using monoclonal antibodies to CD45, CD44 and CD133. The cytokine profiles of ascitic fluid and blood serum (IL-1β, IL-18, IL-4, IL-10 and VEGF) were assessed by ELISA. Stem-like cells were found in all samples. 5 cell populations were evaluated. The number of cells expressing both markers: CD44 + and CD133+, was the lowest. The highest, about 32%, was the number of CD44+ cells. The number of cells CD45-CD44+CD133- in ascites strongly positively correlated with the content of IL-10 in ascites, and the numbers of CD45-CD133+ and CD45-CD44-CD133+ - with the level of VEGF in blood serum. No correlations were found between the numbers of stem-like cells and the disease stage or the level of CA125 in blood. The combination of IL-4 and IL-10 in ascites had the greatest significance in predicting the disease stage. These results suggest a relationship between the levels of VEGF, IL-10, and cancer stem cells in the OC ascites. Stem-like cells in OC ascites are heterogeneous and are present even at an early stage of the disease. It seems promising to study cell populations and cytokine profile of ascites together, to assess the biomarker potential of their combination.

scholarly journals Responses of quinoa (Chenopodium quinoa Willd.) seeds stored under different germination temperatures

2017 ◽  
Vol 39 (1) ◽  
pp. 83 ◽  
Author(s):  
Andressa Strenske ◽  
Edmar Soares de Vasconcelos ◽  
Vanessa Aline Egewarth ◽  
Neusa Francisca Michelon Herzog ◽  
Marlene De Matos Malavasi
Keyword(s):  
Room Temperature ◽  
Storage Time ◽  
Chenopodium Quinoa ◽  
Seed Vigor ◽  
Continuous Darkness ◽  
Experimental Conditions ◽  
Growing Seasons ◽  
Germinating Seeds ◽  
Germinated Seeds ◽  
Plot Design

In this experiment, we assessed the germination and vigor of quinoa seeds packed in paper bags and stored at room temperature for 36, 85, 119, 146, 177 and 270 days. The seeds were harvested under experimental conditions in Marechal Candido Rondon, Paraná, during the 2012/13 growing seasons. Four replicates of 100 seeds each were established for each storage time, and the seeds were evaluated, on paper, based on the BOD under the following experimental temperature conditions: alternating temperatures of 20 and 30°C and a constant temperature of 25°C. The seeds from both treatments were subject to seven-hour photoperiods and 25°C under continuous darkness. The germinated seeds were counted daily for eight days after sowing, and we evaluated the percentages of normal and abnormal seedlings and the germination index. The experimental design was completely randomized using a split-plot design. Increasing the storage time decreased the percentage of germinated seeds and seed vigor due to the increased number of abnormal seedlings. Over the 430-day study period, quinoa seed germination completely declined under the experimental conditions. The final number of germinating seeds should be evaluated 7 days after the beginning of the germination test. 

scholarly journals Materials for Future Quantum Dot-Based Memories

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
T. Nowozin ◽  
D. Bimberg ◽  
K. Daqrouq ◽  
M. N. Ajour ◽  
M. Awedh
Keyword(s):  
Cross Sections ◽  
Room Temperature ◽  
Storage Time ◽  
Thermal Emission ◽  
Current Status ◽  
Strong Electron ◽  
Self Organized ◽  
Hole Confinement ◽  
Storage Times ◽  
Capture Cross Sections

The present paper investigates the current status of the storage times in self-organized QDs, surveying a variety of heterostructures advantageous for strong electron and/or hole confinement. Experimental data for the electronic properties, such as localization energies and capture cross-sections, are listed. Based on the theory of thermal emission of carriers from QDs, we extrapolate the values for materials that would increase the storage time at room temperature to more than millions of years. For electron storage, GaSb/AlSb, GaN/AlN, and InAs/AlSb are proposed. For hole storage, GaSb/Al0.9Ga0.1As, GaSb/GaP, and GaSb/AlP are promising candidates.

The Evolution Behavior of Defects in the Nanofilms of W/Cu and W Probed by Doppler Broadening Positron Annihilation Spectroscopy

2017 ◽  
Vol 373 ◽  
pp. 104-107
Author(s):  
Ling Wang ◽  
Ai Hong Deng ◽  
Kang Wang ◽  
Yong Wang ◽  
Xiao Bo Lu ◽  
...  
Keyword(s):  
Magnetron Sputtering ◽  
Positron Annihilation ◽  
Room Temperature ◽  
Storage Time ◽  
Positron Annihilation Spectroscopy ◽  
Doppler Broadening ◽  
Radio Frequency Magnetron Sputtering ◽  
Helium Ions ◽  
Near Surface ◽  
Evolution Behavior

W/Cu multilayer nanofilms and pure W nanofilms were prepared in pure Ar and He/Ar mixing atmosphere by radio frequency magnetron sputtering method. The defect evolution of the samples was characterized by Doppler broadening positron annihilation spectroscopy (DB-PAS).The results show that plenty of defects can be produced by introducing helium (He) into W/Cu multilayer nanofilms. With the natural storage time increasing, the helium located in the near surface of W/Cu multilayer nanofilm would be released gradually and induce the coalescence of the helium related defects due to the diffusion of the helium and defects. In addition, the pure W nanofilms were irradiated by 30 keV helium ions and 40 keV hydrogen (H) ions in sequence at room temperature. From the DB-PAS analysis, it can be shown that a large number of vacancy-type defects are produced due to the He and/or H irradiation. H ions would be trapped by He related defects and produced He-H-V complexes.

Long-term Room Temperature Instability in Thermal Conductivity of InGaZnO Thin Films

MRS Advances ◽  
2016 ◽  
Vol 1 (22) ◽  
pp. 1631-1636 ◽  
Author(s):  
Boya Cui ◽  
D. Bruce Buchholz ◽  
Li Zeng ◽  
Michael Bedzyk ◽  
Robert P. H. Chang ◽  
...  
Keyword(s):  
Thin Films ◽  
Thermal Conductivity ◽  
Room Temperature ◽  
Storage Time ◽  
Laser Deposition ◽  
Low Oxygen ◽  
X Ray Diffraction ◽  
3Ω Method ◽  
X Ray

ABSTRACTThe cross-plane thermal conductivities of InGaZnO (IGZO) thin films in different morphologies were measured on three occasions within 19 months, using the 3ω method at room temperature 300 K. Amorphous (a-), semi-crystalline (semi-c-) and crystalline (c-) IGZO films were grown by pulsed laser deposition (PLD), followed by X-ray diffraction (XRD) for evaluation of film quality and crystallinity. Semi-c-IGZO shows the highest thermal conductivity, even higher than the most ordered crystal-like phase. After being stored in dry low-oxygen environment for months, a drastic decrease of semi-c-IGZO thermal conductivity was observed, while the thermal conductivity slightly reduced in c-IGZO and remained unchanged in a-IGZO. This change in thermal conductivity with storage time can be attributed to film structural relaxation and vacancy diffusion to grain boundaries.

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