Association of plasma DNA integrity and long fragment ALU247 in the diagnosis of epithelial ovarian cancer

DNA Integrity index (DNA Int) and cell-free DNA (cf-DNA) represent promising biomarkers for epithelial ovarian cancer (EOC) detection. Tumor necrosis produces DNA fractions of different sizes, which contrasts apoptosis in normal tissue that releases smaller and more regular DNA fragments. Using ALU gene primers in quantitative PCR, the amplified cf-DNA is supposed to be either short fragments of 115 bp (ALU 115) or long fragments of 247 bp (ALU 247). ALU levels and DNA Int were determined in the plasma of 30 EOC patients, 30 benign cysts, and 15 healthy individuals. The mean values of DNA Int, ALU115, and ALU247 were elevated in malignant patients (0.51±0.09, 3.93 ng/ul ±1.93, 2.35 ng/ul ±1.1) respectively in comparison to healthy females (0.37±0.05; p < 0.001, 2.56 ng/ul ±0.9; p=0.027, 1.26±0.44; p< 0.01). A significant increase was shown in the mean values of DNA Int and ALU247 of EOC patients compared to those with benign cysts (0.4±0.06, p <0.001; 1.69±0.66, p =0.008) respectively. The area under the curve (AUC) for EOC versus healthy females achieved 0.913 (DNA Int), 0.696 (ALU115), and 0.809 (ALU247) with sensitivities and specificities were (86.7% and 93.3%) for DNA Int, (63.3% and 86.7%) for ALU115 and (76.7% and 86.7%) for ALU247 respectively. Furthermore, comparing patients with EOC versus those with benign cysts gave AUC of 0.834 (DNA Int), 0.564 (ALU115), and 0.681 (ALU247) with sensitivities and specificities were (80% and 80%) for DNA Int, (63.3% and 60%) for ALU115 and (60% and 80%) for ALU247 respectively. Higher DNA Int and plasma ALU247 could help in the assessment of EOC, and their measurements seem to have clinical value in diagnosis.

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Early clearance of serum HE4 and CA125 in predicting platinum sensitivity and prognosis in epithelial ovarian cancer

10.21203/rs.3.rs-44934/v2 ◽

2020 ◽

Author(s):

Yan Rong ◽

Li Li

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Clinical Data ◽

First Line ◽

Clinical Value ◽

Platinum Sensitivity ◽

Platinum Sensitive ◽

Platinum Resistant ◽

Line Chemotherapy ◽

Sensitive Group

Abstract Objectives: To assess the clinical value of early clearance of HE4 and CA125 for platinum sensitivity and prognosis in patients with ovarian cancer.Method: HE4 and CA125 value including clinical data of 89 patients with ovarian cancer were collected. The clearance of HE4 and CA125 were assessed base on the platinum sensitivity, two-year PFS, PFS and OS.Results: 16 patients were classified as platinum resistant and 73 as platinum sensitive according to the response to platinum-base chemotherapy. When HE4 clearance after 3rd cycle chemotherapy or CA125 clearance after 1st cycle chemotherapy, it gave the highest AUC of 0.788, with 100% of sensitivity and 57.5% of specificity respectively between platinum resistant and platinum sensitive group. In addition, 59 patients were classified as two-year PFS group and 30 as not achieved two-year PFS group according to obtaining two-year PFS or not. It gave the highest AUC of 0.730, with 83.3% of sensitivity and 62.7% of specificity respectively when HE4 clearance after 3rd cycle chemotherapy or CA125 clearance after 1st cycle. The prolonged PFS and OS were significantly associated by the clearance of HE4 after 3rd cycle chemotherapy (p<0.0001, p<0.0001) as well as CA125 after 1st cycle chemotherapy (p<0.0001, p<0.0001).Conclusions: Our data suggested that the early clearance of HE4 and CA125 could predict platinum response and prognosis in patients with ovarian cancer. Monitoring the HE4 and CA125 during first-line chemotherapy might be helpful in predicting platinum sensitivity and risk to progress and relapse.

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Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer

Tumor Biology ◽

10.1007/s13277-015-4624-3 ◽

2015 ◽

Vol 37 (6) ◽

pp. 7565-7572 ◽

Cited By ~ 16

Author(s):

Azza M. Kamel ◽

Salwa Teama ◽

Amal Fawzy ◽

Mervat El Deftar

Keyword(s):

Breast Cancer ◽

Diagnostic Marker ◽

Molecular Diagnostic ◽

Dna Integrity ◽

Plasma Dna ◽

Integrity Index

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Determination of carcinoembryonic antigen and cancer antigen values with the radioimmunoassay method in healthy females dogs

Veterinární Medicína ◽

10.17221/6810-vetmed ◽

2013 ◽

Vol 58 (No. 5) ◽

pp. 277-283 ◽

Cited By ~ 9

Author(s):

V. Ledecky ◽

A. Valencakova-Agyagosova ◽

J. Lepej ◽

Z. Frischova ◽

S. Hornak ◽

...

Keyword(s):

Carcinoembryonic Antigen ◽

Statistical Significance ◽

Average Weight ◽

Cancer Antigen ◽

Cancer Markers ◽

Mean Values ◽

The Mean ◽

Radioimmunoassay Method ◽

Healthy Females

The aim of this study was to determine reference values of carcinoembryonic antigen and cancer antigen in 32 clinically healthy bitches. The average age of the bitches in each group was as follows: small breeds 3.50 ± 2.30, medium breeds 3.83 ± 3.21, large breeds 6.00 ± 3.22 and giant breeds 2.40 ± 2.43. The average weight in each group was as follows: 1st group 7.94 kg ± 1.84, 2nd group 22.38 kg ± 2.77, 3rd group 35.94 kg ± 7.16, and 4th group 52.75 kg ± 5.04. The cancer markers were determined using human kits. The mean values of the carcinoembryotic antigen markers ± SD were as follows: 1st group 0.18 ± 0.03, 2nd group 0.20 ± 0.03, 3rd group 0.22 ± 0.01, 4th group 0.18 ± 0.04. The statistical significance for the carcinoembryonic antigen markers was P = 0.0042**. The values of cancer antigen markers ± SD were: 4.90 ± 1.04, 4.80 ± 1.13, 5.90 ± 1.22, and 4.72 ± 0.97, respectively. The cancer antigen values were statistically insignificant (P = 0.1762). Based on obtained values of the mean 95%, we expect a standard for carcinoembryonic antigen of 0.00–0.23 ng/ml and for cancer antigen 0.0–7.00 IU/ml. The results of the present study show that it is possible to use human kits for the determination of carcinoembryonic antigen and cancer antigen in clinically healthy bitches using the radioimmunoassay method.

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Zero order and area under curve spectrophotometric methods for determination of Levocetirizine in pharmaceutical formulation

International Journal of Advances in Scientific Research ◽

10.7439/ijasr.v1i6.2253 ◽

2015 ◽

Vol 1 (6) ◽

pp. 270

Author(s):

Audumbar Digambar Mali ◽

Ritesh Bathe ◽

Manojkumar Patil ◽

Ashpak Tamboli

Keyword(s):

Area Under The Curve ◽

Zero Order ◽

Pharmaceutical Dosage Forms ◽

Mean Values ◽

Spectrophotometric Methods ◽

Ich Guidelines ◽

Significant Difference ◽

Curve Method ◽

The Mean

Simple, fast and reliable spectrophotometric methods were developed for determination of Levocetirizine in bulk and pharmaceutical dosage forms. The solutions of standard and the sample were prepared in methanol. The quantitative determination of the drug was carried out using the zero order derivative values measured at 230 nm and the area under the curve method values measured at 227-234 nm (n=2). Calibration graphs constructed at their wavelengths of determination were linear in the concentration range of Levocetirizine using 5-25?g/ml (r=0.998 and r=0.999) for zero order and area under the curve spectrophotometric method. All the proposed methods have been extensively validated as per ICH guidelines. There was no significant difference between the performance of the proposed methods regarding the mean values and standard deviations. Developed spectrophotometric methods in this study are simple, accurate, precise and sensitive to assay of Levocetirizine in tablets.

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CA125 levels are a weak predictor of optimal cytoreductive surgery in patients with advanced epithelial ovarian cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200303000-00003 ◽

2003 ◽

Vol 13 (2) ◽

pp. 120-124 ◽

Cited By ~ 12

Author(s):

S. Memarzadeh ◽

S. B. Lee ◽

J. S. Berek ◽

R. Farias-Eisner

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cytoreductive Surgery ◽

Predictive Value ◽

Maximal Dimension ◽

Optimal Cytoreduction ◽

Cut Point ◽

Ca125 Level ◽

The Mean ◽

Advanced Epithelial Ovarian Cancer

The utility of preoperative CA125 to predict optimal primary tumor cytoreduction in patients with advanced (stages IIIC and IV) epithelial ovarian cancer is controversial. In this paper, we retrospectively review patients with stage IIIC and IV epithelial ovarian cancer who underwent primary cytoreductive surgery from 1989 to 2001. Ninety-nine patients were identified and included in the analysis. All patients had preoperative CA125 levels measured. Operative and pathology reports were reviewed. Optimal cytoreduction was defined as largest volume of residual disease < 1 cm in maximal dimension. Mean values were compared with t-test on a log scale when needed. The optimal cut-point for discriminating between those with vs. without optimal cytoreduction was determined using the receiver operator curve (ROC) method. Optimal cytoreduction was achieved in 73% of patients. Among patients with optimal cytoreductive status the mean CA125 level was 569, while among patients with suboptimal cytoreduction the mean CA125 level was 1520 (P < 0.007). A CA125 level of 912 was identified as the optimal cut-point to distinguish the two groups. Using this CA125 level, the sensitivity of this test in predicting optimal cytoreduction was 58% and the specificity was 54%. The positive predictive value of CA125 for optimal cytoreduction was 78% and the negative predictive value was 31%. We conclude that CA125 level is a weak positive and negative predictor of optimal cytoreductive surgery in patients with advanced epithelial ovarian cancer. The CA125 level should not be used as a primary predictor of the outcome of cytoreductive surgery and should be viewed in the context of all other preoperative features.

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Discordant GH and IGF-1 Results in Treated Acromegaly: Impact of GH Cutoffs and Mean Values Assessment

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa859 ◽

2020 ◽

Author(s):

Claudia Campana ◽

Francesco Cocchiara ◽

Giuliana Corica ◽

Federica Nista ◽

Marica Arvigo ◽

...

Keyword(s):

Characteristic Curve ◽

Area Under The Curve ◽

Receiver Operator Characteristic Curve ◽

Mean Values ◽

Pituitary Diseases ◽

Discordance Rate ◽

Values Assessment ◽

The Mean ◽

The Impact

Abstract Context Discordant growth hormone (GH) and insulin-like growth factor-1 (IGF-1) values are frequent in acromegaly. Objective To evaluate the impact of different GH cutoffs on discordance rate. To investigate whether the mean of consecutive GH measurements impacts discordance rate when matched to the last available IGF-1 value. Design Retrospective study. Setting Referral center for pituitary diseases. Patients Ninety acromegaly patients with at least 3 consecutive evaluations for GH and IGF-1 using the same assay in the same laboratory (median follow-up 13 years). Interventions Multimodal treatment of acromegaly. Main Outcome Measures Single fasting GH (GHf) and IGF-1 (IGF-1f). Mean of 3 GH measurements (GHm), collected during consecutive routine patients’ evaluations. Results At last evaluation GHf values were 1.99 ± 2.79 µg/L and age-adjusted IGF-1f was 0.86 ± 0.44 × upper limit of normality (mean ± SD). The discordance rate using GHf was 52.2% (cutoff 1 µg/L) and 35.6% (cutoff 2.5 µg/L) (P = 0.025). “High GH” discordance was more common for GHf <1.0 µg/L, while “high IGF-1” was predominant for GHf <2.5 µg/L (P < 0.0001). Using GHm mitigated the impact of GH cutoffs on discordance (GHm <1.0 µg/L: 43.3%; GHm <2.5 µg/L: 38.9%; P = 0.265). At receiver-operator characteristic curve (ROC) analysis, both GHf and GHm were poor predictors of IGF-1f normalization (area under the curve [AUC] = 0.611 and AUC = 0.645, respectively). The prevalence of disease-related comorbidities did not significantly differ between controlled, discordant, and active disease patients. Discussion GH/IGF-1 discordance strongly depends on GH cutoffs. The use of GHm lessen the impact of GH cutoffs. Measurement of fasting GH levels (both GHf and GHm) is a poor predictor of IGF-1f normalization in our cohort.

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RBM3-Regulated Genes Promote DNA Integrity and Affect Clinical Outcome in Epithelial Ovarian Cancer

Translational Oncology ◽

10.1593/tlo.11106 ◽

2011 ◽

Vol 4 (4) ◽

pp. 212-IN1 ◽

Cited By ~ 30

Author(s):

Õsa Ehlén ◽

Björn Nodin ◽

Elton Rexhepaj ◽

Jenny Brändstedt ◽

Mathias Uhlén ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Outcome ◽

Epithelial Ovarian Cancer ◽

Dna Integrity

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Evaluation of prediction score of contrast-induced nephropathy in inpatients undergone to digital or CT angiography

REVISTA CIÊNCIAS EM SAÚDE ◽

10.21876/rcshci.v10i3.974 ◽

2020 ◽

Vol 10 (3) ◽

pp. 78-84

Author(s):

Seleno Glauber de Jesus-Silva ◽

Ana Elisa Chaves ◽

Caio Augusto Alves Maciel ◽

Edson Eziel Ferreira Scotini ◽

Pablo Girardelli Mendonça Mesquita ◽

...

Keyword(s):

Computed Tomography ◽

Roc Curve ◽

Computed Tomography Angiography ◽

Score Test ◽

Area Under The Curve ◽

Roc Curve Analysis ◽

Contrast Induced Nephropathy ◽

Mean Values ◽

Iodinated Contrast ◽

The Mean

Objectives: To assess the incidence of contrast-induced nephropathy (CIN) and determine the Mehran Score's (MS) ability to predict CIN in patients undergoing digital angiography or computed tomography angiography. Methods: 252 medical records of inpatients who underwent DA or CTA over 28 months in a quaternary hospital were reviewed. CIN was defined as serum creatinine> 0.5 mg / dL or > 25% increase in baseline creatinine, 48 h after administration of iodinated contrast. The ROC curve and the area under the curve (AUC) were used as a score test. Results: The majority (159; 63.1%) were male, and the average age was 60.4 years. Anemia, diabetes mellitus, and age > 75 years were the most prevalent factors. The incidence of CIN was 17.8% (n = 45). There was a decrease in the mean values of creatinine pre and post among patients who did not suffer CIN (1.38 ± 1.22 vs 1.19 ± 0.89; t = 3.433; p = 0.0007), while among patients who suffering CIN, the mean increase was 1.03 mg / dL (1.43 ± 1.48 vs 2.46 ± 2.35 mg / dL; t = 5.44; p = 0.117). The ROC curve analysis identified a low correlation between MS and the occurrence of CIN (AUC = 0.506). Conclusion: The incidence of CIN in hospitalized patients undergoing angiography or computed tomography angiography was high. The EM did not allow the prediction of NIC.

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Variation of the anal resting pressure induced by postexpiratory apnea effort in patients with constipation

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032011000100007 ◽

2011 ◽

Vol 48 (1) ◽

pp. 30-35

Author(s):

Thaís Helena Benetti ◽

Maria Fernanda Santos ◽

Melissa Eichenberger Alves Mergulhão ◽

João José Fagundes ◽

Maria de Lourdes Setsuko Ayrizono ◽

...

Keyword(s):

Pelvic Floor ◽

Valsalva Maneuver ◽

Area Under The Curve ◽

Pressure Variation ◽

Common Symptom ◽

Forced Expiration ◽

Anal Pressure ◽

Mean Values ◽

Anal Orifice ◽

The Mean

CONTEXT: Intestinal constipation - a common symptom among the general population - is more frequent in women. It may be secondary to an improper diet or organic or functional disturbances, such as dyskinesia of the pelvic floor. This is basically characterized by the absence of relaxation or paradoxical contraction of the pelvic floor and anal sphincter during evacuation. OBJECTIVE: To analyze, by manometric data, the anal pressure variation at rest, during evacuation effort by using the Valsalva maneuver and forced post-expiratory apnea in subjects with secondary constipation. METHODS: Twenty-one patients (19 females - 90.4%) with a mean age of 47.5 years old (23-72) were studied. The diagnosis was performed using anorectal manometry, with a catheter containing eight channels disposed at the axial axis, measuring the proximal (1) and distal (2) portions of the anal orifice. The elevation of the pressure values in relation to the resting with the evacuation effort was present in all patients. The Agachan score was used for clinical evaluation of constipation. The variables studied were: mean anal pressure of the anal orifice for 20 seconds at rest, the effort of evacuation using Valsalva maneuver and the effort of evacuation during apnea after forced expiration, as well as the area under the curve of the manometric tracing at moments Valsalva and apnea. RESULTS: The analysis of the mean values of the anal pressure variation at rest evidenced difference between proximal and distal channels (P = 0.007), independent of the moment and tendency to differ during moments Valsalva and apnea (P = 0.06). The mean of values of the area under the manometric tracing curve showed differences between moments Valsalva and apnea (P = 0.0008), either at the proximal portion or at the distal portion of the anal orifice. CONCLUSION: The effort of evacuation associated with postexpiratory apnea, when compared with the effort associated with the Valsalva maneuver, provides lower elevation of anal pressure at rest by the parameter area under the curve.

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the ‘Area Under the Curve’ or AUC. The AUC is taken as a measure of exposure of the drug to the subject. The peak or maximum concen-tration is referred to as Cmax and is an important safety measure. For regulatory approval of bioequivalence it is necessary to show from the trial results that the mean values of AUC and Cmax for T and R are not signiﬁcantly diﬀerent. The AUC is calculated by adding up the ar-eas of the regions identiﬁed by the vertical lines under the plot in Figure 7.1 using an arithmetic technique such as the trapezoidal rule (see, for example, Welling, 1986, 145–149, Rowland and Tozer, 1995, 469–471). Experience (e.g., FDA Guidance, 1992, 1997, 1999b, 2001) has dictated that AUC and Cmax need to be transformed to the natural logarithmic scale prior to analysis if the usual assumptions of normally distributed errors are to be made. Each of AUC and Cmax is analyzed separately and there is no adjustment to signiﬁcance levels to allow for multiple testing (Hauck et al., 1995). We will refer to the derived variates as log(AUC) and log(Cmax), respectively. In bioequivalence trials there should be a wash-out period of at least ﬁve half-lives of the drugs between the active treatment periods. If this is the case, and there are no detectable pre-dose drug concentrations, there is no need to assume that carry-over eﬀects are present and so it is not necessary to test for a diﬀerential carry-over eﬀect (FDA Guidance, 2001). The model that is ﬁtted to the data will be the one used in Section 5.3 of Chapter 5, which contains terms for subjects, periods and treatments. Following common practice we will also ﬁt a sequence or group eﬀect and consider subjects as a random eﬀect nested within sequence. An example of ﬁtting this model will be given in the next section. In the following sections we will consider three forms of bioequivalence: average (ABE), population (PBE) and individual (IBE). To simplify the following discussion we will refer only to log(AUC); the discussion for log(Cmax) is identical. To show that T and R are average bioequivalent it is only necessary to show that the mean log(AUC) for T is not signiﬁcantly diﬀerent from the mean log(AUC) for R. In other words we need to show that, ‘on average’, in the population of intended patients, the two drugs are bioequivalent. This measure does not take into account the variability of T and R. It is possible for one drug to be much more variable than the other, yet be similar in terms of mean log(AUC). It was for this reason that PBE was introduced. As we will see in Section 7.5, the measure of PBE that has been recommended by the regulators is a mixture of the mean and variance of the log(AUC) values (FDA Guidance, 1997, 1999a,b, 2000, 2001). Of course, two drugs could be similar in mean and variance over the

Design and Analysis of Cross-Over Trials ◽

10.1201/9781420036091-5 ◽

2003 ◽

pp. 350-350

Keyword(s):

Multiple Testing ◽

Random Effect ◽

Area Under The Curve ◽

Mean Values ◽

Fda Guidance ◽

Significance Levels ◽

Mean And Variance ◽

The Mean ◽

Carry Over ◽

The One

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