scholarly journals Blood bioactive sphingolipids in patients with advanced serous epithelial ovarian cancer – mass spectrometry analysis

2021 ◽  
Vol 17 (1) ◽  
pp. 53-61
Author(s):  
Paweł Knapp ◽  
Lubomir Bodnar ◽  
Agnieszka Błachnio-Zabielska ◽  
Joanna Reszeć ◽  
Magdalena Świderska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Advanced Ovarian Cancer ◽  
Mass Spectrometry Analysis ◽  
Control Group ◽  
Serous Ovarian Cancer ◽  
Figo Staging ◽  
Sphingosine 1 Phosphate ◽  
Bioactive Sphingolipids

IntroductionDue to the lack of highly specific and sensitive methods for diagnosing ovarian cancer at advanced stages (according to the International Federation of Gynecology and Obstetrics (FIGO) classification stage III–IV), new noninvasive biomarkers are urgently needed. This study aims to investigate how the levels of plasma bioactive sphingolipids (ceramides, sphingosine-1-phosphate, sphingosine and sphinganine) are altered in serum, erythrocytes and platelets of patients with advanced serous ovarian cancer.Material and methodsA total of 135 patients with advanced serous ovarian cancer and 159 women with normal ovarian morphology were enrolled. Plasma levels of sphingosine, sphingosine-1-phosphate, sphinganine, ceramide C14:0-Cer, C16:0-Cer, C18:1-Cer, C18:0-Cer, C20:0-Cer, C22:0-Cer, C24:1-Cer and C24:0-Cer were assessed by LC/MS/MS.ResultsPlasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were significantly higher in the advanced ovarian cancer group than in the control group (1.5-fold, p = 0.021; 1.8-fold, p = 0.036 and 1.5-fold, p = 0.031, respectively). Plasma concentration of C18:1-Cer was significantly higher in erythrocytes of women with advanced serous cancer compared to the control group (p = 0.027). Plasma C16-Cer and C18:1-Cer levels and erythrocyte C18:1-Cer levels were able to distinguish patients with moderate/severe serous ovarian cancer from patients with mild ovarian cancer (AUC: 0.86, 0.898, 0.795, respectively). Plasma concentrations of C16, C18.1 and C18 significantly correlated with FIGO staging (p = 0.001, p = 0.024 and p = 0.005), and grading (p = 0.021, p = 0.021 and p = 0.033).ConclusionsPlasma concentrations of C16, C18.1 and C18 correlated with the progression of ovarian cancer (FIGO staging and grading). Plasma levels of C16-Cer and C18:1-Cer and erythrocyte C18:1-Cer levels could be used to distinguish patients with advanced serous ovarian cancer.

scholarly journals Evaluation of Collagen Alterations in Early Precursor Lesions of High Grade Serous Ovarian Cancer by Second Harmonic Generation Microscopy and Mass Spectrometry

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2794
Author(s):  
Kristal L. Gant ◽  
Alexander N. Jambor ◽  
Zihui Li ◽  
Eric C. Rentchler ◽  
Paul Weisman ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ovarian Cancer ◽  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Collagen Fiber ◽  
Second Harmonic ◽  
Mass Spectrometry Analysis ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Fiber Morphology

Background: The collagen architecture in high grade serous ovarian cancer (HGSOC) is highly remodeled compared to the normal ovary and the fallopian tubes (FT). We previously used Second Harmonic Generation (SHG) microscopy and machine learning to classify the changes in collagen fiber morphology occurring in serous tubal intraepithelial carcinoma (STIC) lesions that are concurrent with HGSOC. We now extend these studies to examine collagen remodeling in pure p53 signatures, STICs and normal regions in tissues that have no concurrent HGSOC. This is an important distinction as high-grade disease can result in distant collagen changes through a field effect mechanism. Methods: We trained a linear discriminant model based on SHG texture and image features as a classifier to discriminate the tissue groups. We additionally performed mass spectrometry analysis of normal and HGSOC tissues to associate the differential expression of collagen isoforms with collagen fiber morphology alterations. Results: We quantified the differences in the collagen architecture between normal tissue and the precursors with good classification accuracy. Through proteomic analysis, we identified the downregulation of single α-chains including those for Col I and III, where these results are consistent with our previous SHG-based supramolecular analyses. Conclusion: This work provides new insights into ECM remodeling in early ovarian cancer and suggests the combined use of SHG microscopy and mass spectrometry as a new diagnostic/prognostic approach.

Abstract 3476: Higher plasma levels of heparan sulfate are associated with improved survival of patients with advanced ovarian cancer.

2013 ◽  
Author(s):  
Matthew S. Block ◽  
Matthew J. Maurer ◽  
Krista M. Goergen ◽  
Courtney L. Erskine ◽  
Marshall D. Behrens ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Heparan Sulfate ◽  
Plasma Levels ◽  
Advanced Ovarian Cancer

scholarly journals Plasma Concentrations of Matrilysins MMP-7 and MMP-26 as Diagnostic Biomarkers in Breast Cancer

2021 ◽  
Vol 10 (7) ◽  
pp. 1436
Author(s):  
Barbara Maria Piskór ◽  
Andrzej Przylipiak ◽  
Emilia Dąbrowska ◽  
Iwona Sidorkiewicz ◽  
Marek Niczyporuk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Plasma Levels ◽  
Proteolytic Enzymes ◽  
Plasma Concentrations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Diagnostic Utility ◽  
Study Results ◽  
Advanced Stages ◽  
Disease Study

Metalloproteinases (MMPs) are a group of proteolytic enzymes involved in the maintenance of a proper structure of extracellular matrix (ECM). Matrilysins (MMP-7 and MMP-26) are members of the MMPs group that show promise as potential breast cancer (BC) markers. The aim of the study was to evaluate plasma levels of MMP-7, MMP-26 and CA 15-3 individually and in combination and assess the diagnostic utility of studied matrilysins in patients with BC. The study group consisted of 120 patients with BC, and the control group consisted of 40 subjects with benign breast cancer and 40 healthy women. Concentrations of MMP-7 and MMP-26 were determined by enzyme-linked immunosorbent assay, and CA 15-3 by chemiluminescent microparticle immunoassay. Plasma levels of MMP-7 were significantly higher in the BC group than in the control group. Concentrations of MMP-26 and CA 15-3 were highest in stages II and IV of the disease. The highest diagnostic sensitivity was observed in stages III and IV BC for the combination of all tested markers (92.5%). The highest diagnostic specificity was noted for all tested parameters combined in the BC group (95.0%). The area under the receiver operating characteristic (ROC) curve (AUC) for the combination of markers (MMP-7+MMP-26+CA 15-3) was the largest (0.9138) in stages III and IV. Individual marker analysis showed that MMP-7 had the highest AUC (0.8894) in advanced stages of the disease. Study results indicate that MMP-7 could be used as an additional marker that would improve the diagnostic utility of CA 15-3 in early stages of BC. Therefore, the combined assessment of MMP-7 and MMP-26 with CA 15-3 might be useful in determining disease progression. Further studies are needed to evaluate whether matrilysins show promise as potential markers for improving the diagnosis of BC.

Imatinib Plasma Levels and Its Correlation with Response in Chronic-Phase Chronic Myeloid Leukemia: Experience of One Centre.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4284-4284
Author(s):  
J. Valentin Garcia. Gutierrez ◽  
Jesús Odriozola ◽  
Pilar Herrera ◽  
Javier Lopez ◽  
Maria Calbacho ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Plasma Levels ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Plasma Concentrations ◽  
Chronic Phase ◽  
Control Group ◽  
Treatment Optimisation ◽  
Number Of Patients

Abstract Abstract 4284 Introduction Imatinib (IM), 400 mg/d. induces durable responses in chronic myeloid leukaemia (CML) in chronic phase (CP). However, although IM-biodisponibility is fairly good, its plasma levels are variable and can not be predicted. Recently, these plasma concentrations have been related both to the dose being administrated and to the cytogenetic and molecular responses. Thus, Imatinib pharmacokinetics could be an issue towards treatment optimisation in CML patients. Recent studies suggest that therapeutic IM plasma levels should be above 1040 ng/dl. Aims To evaluate the association between IM dose and throughout plasma levels with different clinical outcomes. Results In this study, we looked for an association between plasma concentrations and clinical outcomes in 16/86 CML chronic phase patients who did not achieve optimal responses following the European Leukemia Net guidelines (ELN) (table 1). Patients with optimal responses and treated with the same standard doses were also analysed as a control group. Patients receiving doses above 400 mg showed throughout plasma levels considered as appropriate. In 7 of 16 patients (47.5%) not achieving optimal responses (ELN criteria), plasma levels were below the supposed therapeutic ranges. We have found no evidence for a correlation between clinical risk factors at diagnosis and the measurement of optimal plasma levels. Conclusions IM plasma levels are well correlated with IM dose administrated in the patients studied. In almost 50% of patients who did not achieve optimal responses, IM plasma levels were under the ranges considered therapeutic. Probably these are the patients who may benefit of a dose increase. Obviously, to learn more about the practical value of these measurements a longer follow up with a larger number of patients is needed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Dietary Intake and Plasma Levels of Choline and Betaine in Children with Autism Spectrum Disorders

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Joanna C. Hamlin ◽  
Margaret Pauly ◽  
Stepan Melnyk ◽  
Oleksandra Pavliv ◽  
William Starrett ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Research Network ◽  
Control Group ◽  
Lower Plasma ◽  
One Carbon Metabolism ◽  
Positive Correlations

Abnormalities in folate-dependent one-carbon metabolism have been reported in many children with autism. Because inadequate choline and betaine can negatively affect folate metabolism and in turn downstream methylation and antioxidant capacity, we sought to determine whether dietary intake of choline and betaine in children with autism was adequate to meet nutritional needs based on national recommendations. Three-day food records were analyzed for 288 children with autism (ASDs) who participated in the national Autism Intervention Research Network for Physical Health (AIR-P) Study on Diet and Nutrition in children with autism. Plasma concentrations of choline and betaine were measured in a subgroup of 35 children with ASDs and 32 age-matched control children. The results indicated that 60–93% of children with ASDs were consuming less than the recommended Adequate Intake (AI) for choline. Strong positive correlations were found between dietary intake and plasma concentrations of choline and betaine in autistic children as well as lower plasma concentrations compared to the control group. We conclude that choline and betaine intake is inadequate in a significant subgroup of children with ASDs and is reflected in lower plasma levels. Inadequate intake of choline and betaine may contribute to the metabolic abnormalities observed in many children with autism and warrants attention in nutritional counseling.

Primary Headaches: Reduced Circulating β-Lipotropin and β-Endorphin Levels with Impaired Reactivity to Acupuncture

Cephalalgia ◽  
1981 ◽  
Vol 1 (4) ◽  
pp. 195-201 ◽  
Author(s):  
F. Facchinetti ◽  
G. Nappi ◽  
F. Savoldi ◽  
A. R. Genazzani
Keyword(s):  
Healthy Volunteers ◽  
Plasma Levels ◽  
Chronic Headache ◽  
Plasma Concentrations ◽  
Primary Headache ◽  
Control Group ◽  
Primary Headaches ◽  
Chinese Acupuncture ◽  
Daily Chronic Headache

Eleven patients affected by common migraine (CM), eleven affected by daily chronic headache (DCH), and eight healthy volunteers were studied. Plasma levels of β-endorphin (βEP), β-lipotropin (βLPH), ACTH and cortisol were measured in basal conditions and after traditional Chinese acupuncture (TCA). Basal βLPH and βEP plasma levels (pg/ml) in the DCH patients (57.6 ± 9.5 and 16.8 ± 2.5, respectively; M ± SE) were lower than those found in the controls (83.6 ± 13.7 and 26.0 ± 6.1; p < 0.001), while those found in the CM cases showed intermediate values (75.3 ± 12.0 and 24.4 ± 5.8). ACTH and cortisol concentrations in both the CM and DCH patients were in the same range as those of the control group. TCA caused an increase in βLPH and βEP plasma concentrations in the control group (βLPH: 117 ± 16.9; βEF: 44.6 ± 6.7). Opioid plasma levels, however, remained unmodified after TCA in both the CM and DCH groups. ACTH plasma levels remained stable after TCA in all three subject groups. Patients suffering from primary headache are characterized by low βLPH and βEP plasma levels and by a poor reactivity of circulating opioids to non-stressful stimuli.

scholarly journals Toll-like Receptor 2 as a Marker Molecule of Advanced Ovarian Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1205
Author(s):  
Małgorzata Sobstyl ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Rafał Hrynkiewicz ◽  
Dominika Bębnowska ◽  
Izabela Korona-Głowniak ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Screening Tests ◽  
Control Group ◽  
Newly Diagnosed ◽  
Toll Like Receptor ◽  
Tlr2 Expression ◽  
Diagnostic Approaches ◽  
Toll Like Receptor 2 ◽  
Marker Molecule

Ovarian cancer is a global problem that affects women of all ages. Due to the lack of effective screening tests and the usually asymptomatic course of the disease in the early stages, the diagnosis is too late, with the result that less than half of the patients diagnosed with ovarian cancer (OC) survive more than five years after their diagnosis. In this study, we examined the expression of TLR2 in the peripheral blood of 50 previously untreated patients with newly diagnosed OC at various stages of the disease using flow cytometry. The studies aimed at demonstrating the usefulness of TLR2 as a biomarker in the advanced stage of ovarian cancer. In this study, we showed that TLR2 expression levels were significantly higher in women with more advanced OC than in women in the control group. Our research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and thus in increasing survival in patients with confirmed ovarian cancer.

TRAINING-Ovary 01 (connecTed pRehabiliAtIoN pelvIc caNcer surGery): multicenter randomized study comparing neoadjuvant chemotherapy for patients managed for ovarian cancer with or without a connected pre-habilitation program

2020 ◽  
pp. ijgc-2020-002128
Author(s):  
Eric Lambaudie ◽  
Cécile Bannier/Braticevic ◽  
Charlène Villaron/Goetgheluck ◽  
Christophe Zemmour ◽  
Jean-Marie Boher ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Primary Endpoint ◽  
Advanced Ovarian Cancer ◽  
Well Being ◽  
Phase Iii ◽  
Pelvic Surgery ◽  
Control Group ◽  
Gynecology And Obstetrics ◽  
Pelvic Cancer

BackgroundPatients undergoing neoadjuvant chemotherapy before surgery for advanced ovarian cancer may have impaired functional capacity, nutritional status, and emotional well-being.Primary objective(s)TRAINING-01 aims to determine if a connected pre-habilitation program during neoadjuvant chemotherapy for patients treated for an advanced ovarian cancer will improve physical capacity before major abdomino-pelvic surgery.Study hypothesisA pre-habilitation program during neoadjuvant chemotherapy will bring a fitter patient to surgery and will decrease treatment morbidity and improve oncological outcomes.Trial designThis study is a prospective, multi-center, phase III study. The pre-habilitation program consists of providing multi-dimensional support during neoadjuvant chemotherapy using connected devices. The control group will receive usual care.Major inclusion/exclusion criteriaEligible patients will be women with International Federation of Gynecology and Obstetrics stage III–IV advanced ovarian cancer undergoing neoadjuvant chemotherapy. Patients must be able to perform a cardiopulmonary exercise test.Primary endpoint(s)The primary endpoint will be the comparison of the variation in maximum oxygen uptake (VO2 max) between baseline and surgery in the pre-habilitation group and control groups.Sample size136 patients (68 per arm) will be recruited to demonstrate a medium standardized effect d=0.5 in the variations of VO2 max between baseline and surgery.Estimated dates for completing accrual and presenting resultsThe duration of the study includes 24 months of recruitment and 5 years of follow up. We anticipate reporting primary endpoint results in 2024.Trial registrationTRAINING-01-IPC 2018-039 (NCT04451369).

Impact of clinical factors and surgical outcome on long-term survival in high-grade serous ovarian cancer: a multicenter analysis

2021 ◽  
pp. ijgc-2020-002023
Author(s):  
Joanna Baum ◽  
Elena Ioana Braicu ◽  
Oliver Hunsicker ◽  
Ignace Vergote ◽  
Nicole Concin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Control Group ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Term Survival ◽  
Long Term Survival ◽  
Tumor Involvement ◽  
Upper Abdomen ◽  
Long Term Survivors

IntroductionLong-term survivors of ovarian cancer are a unique group of patients in whom prognostic factors for long-term survival have been poorly described. Such factors may provide information for a more personalized therapeutic approach. The objective of this study is to determine further characteristics of long-term survivors with high-grade serous ovarian cancer.MethodsLong-term survivors were defined as patients living longer than 8 years after first diagnosis and were recruited within seven high volume centers across Europe from November 1988 to November 2008. The control group included patients with high-grade serous ovarian cancer with less than 5 years' survival identified from the systematic ‘Tumorbank ovarian cancer’ database. A subanalysis of Charité patients only was performed separately for in-depth analysis of tumor dissemination. Propensity score matching with nearest-neighbor caliper width was used to match long-term survivors and the control group regarding age, FIGO stage, and residual tumor.ResultsA total of 276 patients with high-grade serous ovarian cancer were included, divided into 131 long-term survivors and 145 control group patients. After propensity score matching and multivariable adjustment, platinum sensitivity (p=0.002) was an independent favorable prognostic factor whereas recurrence (p<0.001) and ascites (p=0.021) were independent detrimental predictors for long-term survival. Significantly more long-term survivors tested positive for mutation in the BRCA1 gene than the BRCA2 gene (p=0.016). Intraoperatively, these patients had less tumor involvement of the upper abdomen at initial surgery (p=0.024). Complexity of surgery and surgical techniques were similar in both cohorts.ConclusionPlatinum sensitivity constitutes a favorable factor for long-term survival whereas tumor involvement of the upper abdomen, ascites, and recurrence have a negative impact. Based on clinical estimation, long-term survival is associated with combinations of clinical, surgical, and molecular factors.

scholarly journals Effects of interleukin-3 after chemotherapy for advanced ovarian cancer

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1141-1148 ◽  
Author(s):  
B Biesma ◽  
PH Willemse ◽  
NH Mulder ◽  
DT Sleijfer ◽  
JA Gietema ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Side Effects ◽  
Plasma Levels ◽  
Liver Toxicity ◽  
Advanced Ovarian Cancer ◽  
Maximum Tolerated Dose ◽  
Necrosis Factor Alpha ◽  
Interleukin 3 ◽  
Amyloid A ◽  
Facial Erythema

Abstract To define the maximum tolerated dose and to study whether recombinant human interleukin-3 (rhIL-3) reduced chemotherapy-induced neutropenia and thrombocytopenia, 20 chemotherapy-naive patients with advanced ovarian cancer eligible for treatment with 6 cycles of carboplatin- cyclophosphamide every 4 weeks (day 1) were entered in a phase I/II open, single-center trial. Cohorts of five patients received during 7 days 1, 5, 10, or 15 micrograms/kg/d rhIL-3 (days 5 through 11) in cycles 1, 3, and 5 by continuous intravenous (IV) infusion or once daily subcutaneous (SC) administration. In control cycles 2, 4, and 6, no rhIL-3 was administered. rhIL-3 significantly increased the recovery of leukocyte, neutrophil, and platelet counts, especially at 5, 10, and 15 micrograms/kg rhIL-3. rhIL-3 also increased basophil, eosinophil, monocyte, and lymphocyte counts at this dose steps. Effects on reticulocytes were limited. No difference in efficacy between SC and IV rhIL-3 treatment was found. Chemotherapy postponement for insufficient bone marrow recovery was necessary in 22 of 45 control cycles versus 2 of 49 rhIL-3 cycles (P less than .001). Platelet transfusions were required in 7 of 45 control cycles versus 3 of 50 rhIL-3 cycles (P less than .5). rhIL-3 up to 10 micrograms/kg/d could be administered without severe side effects. At 15 micrograms/kg/d, rhIL-3 headache was dose- limiting. Other side effects were fever, flu-like symptoms, nausea, skin rash, flushing, facial erythema, and urticaria. Liver toxicity occurred in rhIL-3 and control cycles. rhIL-3 slightly increased tumor necrosis factor alpha, C-reactive protein, and serum amyloid A plasma levels, whereas no effect on IL-6 plasma levels was observed. rhIL-3 administered SC appears to be an interesting hematopoietic growth factor for reduction of chemotherapy-induced myelotoxicity.

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