scholarly journals Identification of potential metabolic biomarkers of rectal cancer and of the effect of neoadjuvant radiochemotherapy

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250453
Author(s):  
Elisabet Rodríguez-Tomàs ◽  
Meritxell Arenas ◽  
Junior Gómez ◽  
Johana Acosta ◽  
Jordi Trilla ◽  
...  

We report a pilot study on the feasibility of determinations of circulating levels of paraoxonase-1 (PON1) and compounds related to energy metabolism as biomarkers for the evaluation of patients with rectal cancer (RC), and the effects produced by neoadjuvant radiochemotherapy (NRCT). We studied 32 patients treated with radiotherapy plus capecitabine concomitant chemotherapy and 48 control subjects. We identified pre-NRCT PON1 and α-ketoglutarate as the parameters that best discriminated between RC patients and the control group. Receiver operating characteristics analysis of the combination of the two parameters showed an area under the curve (AUC) of 0.918. Moreover, patients who presented a pathological complete response (pCR) to treatment had lower plasma pre-NRCT valine concentrations (AUC of 0.826). Patients who had a relapse had lower concentrations of succinate (AUC of 0.833). The results of the present study illustrate the usefulness of investigating alterations in oxidative stress and metabolism in RC. Due to the small number of patients studied, our results must be considered preliminary, but they suggest that the determination of circulating levels of PON1 and α-ketoglutarate might be a valuable tool for the early diagnosis of RC, while the determination of valine and succinate might effectively predict pCR and the appearance of relapse.

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2603
Author(s):  
Katarzyna Szczeklik ◽  
Tomasz Mach ◽  
Dorota Cibor ◽  
Danuta Owczarek ◽  
Jacek Sapa ◽  
...  

Diagnostics of Crohn’s disease (CD) requires noninvasive biomarkers facilitating early detection and differentiation of the disease. Therefore, in this study, we aimed to determine the relationship between paraoxonase-1 (PON-1), the severity of CD, oxidative stress, and inflammation in CD. The CD activity index was based on the current classification. Plasma PON-1 was measured in 47 patients with CD, and in 23 control volunteers. Using quantitative variables such as receiver operating characteristics (ROC) (area under the curve (AUC)), the diagnostic utility of PON-1 in differentiating the severity of CD was assessed. Circulating PON-1 was found to be decreased in the CD group compared to the control group (269.89 vs. 402.56 U/L, respectively), and it correlated well with the disease activity. PON-1 correlated positively with hemoglobin (Hb) (r = 0.539, p < 0.001), hematocrit (Ht) (r = 0.48, p < 0.001), total cholesterol (TC) (r = 0.343, p < 0.001), high density lipoprotein (HDL) (r = 0.536, p < 0.001), low density lipoprotein (LDL) (r = 0.54, p < 0.001), and triglyceride (TG) (r = 0.561, p < 0.001) and correlated negatively with white blood cell count (WBC) (r = −0.262, p = 0.029), platelet count (PLT) (r = −0.326, p = 0.006), C-reactive protein (CRP) (r = −0.61, p < 0.001), and malondialdehyde (MDA) (r = −0.924, p < 0.001). PON-1 as a marker for CD differentiation possessed a sensitivity and specificity of 93.62% and 91.30%, respectively. CD was found to be associated with the decrease in the levels of PON-1, which correlates well with activity of the disease and reflects the intensification of inflammation, as well as intensified lipid peroxidation. High sensitivity and specificity of PON-1 determines its selection as a good screening test for CD severity.


Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1551 ◽  
Author(s):  
Edyta Marta Borkowska ◽  
Tomasz Konecki ◽  
Michał Pietrusiński ◽  
Maciej Borowiec ◽  
Zbigniew Jabłonowski

Bladder cancer (BC) is still characterized by a very high death rate in patients with this disease. One of the reasons for this is the lack of adequate markers which could help determine the biological potential of the tumor to develop into its invasive stage. It has been found that some microRNAs (miRNAs) correlate with disease progression. The purpose of this study was to identify which miRNAs can accurately predict the presence of BC and can differentiate low grade (LG) tumors from high grade (HG) tumors. The study included 55 patients with diagnosed bladder cancer and 30 persons belonging to the control group. The expression of seven selected miRNAs was estimated with the real-time PCR technique according to miR-103-5p (for the normalization of the results). Receiver operating characteristics (ROC) curves and the area under the curve (AUC) were used to evaluate the feasibility of using selected markers as biomarkers for detecting BC and discriminating non-muscle invasive BC (NMIBC) from muscle invasive BC (MIBC). For HG tumors, the relevant classifiers are miR-205-5p and miR-20a-5p, whereas miR-205-5p and miR-182-5p are for LG (AUC = 0.964 and AUC = 0.992, respectively). NMIBC patients with LG disease are characterized by significantly higher miR-130b-3p expression values compared to patients in HG tumors.


2021 ◽  
Vol 11 (2) ◽  
pp. 19-28
Author(s):  
Z. Z. Mamedli ◽  
A. V. Polynovskiy ◽  
D. V. Kuzmichev ◽  
S. I. Tkachev ◽  
A. A. Aniskin

The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.


Antioxidants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 213 ◽  
Author(s):  
Elisabet Rodríguez-Tomàs ◽  
Mauricio Murcia ◽  
Meritxell Arenas ◽  
Mònica Arguís ◽  
Miriam Gil ◽  
...  

We investigated alterations in the levels of the antioxidant paraoxonase-1 (PON1) and the lipoprotein profile (analyzed by nuclear magnetic resonance) in patients with lung cancer (LC) or head and neck cancer (HNC), and the effects produced thereon by radiotherapy (RT). We included 33 patients with LC and 28 patients with HNC. Before irradiation, and one month after completion of RT, blood samples were obtained. The control group was composed of 50 healthy subjects. Patients had significantly lower serum PON1 activity and concentration before RT than the control group. PON1-related variables were good predictors of the presence of LC or HNC, with analytical sensitivities and specificities greater than 80%. Patients showed a significant increase in the number of particles of all subclasses of very-low-density lipoproteins (large, medium and small). However, these changes were not maintained when adjusted for age, sex, and other clinical and demographic variables. Irradiation was associated with a significant increase in PON1 concentration and, only in patients with HNC, with an increase in high-density lipoprotein-cholesterol concentration. Our results suggest that determinations of the levels of PON1-related variables may constitute good biomarkers for the evaluation of these diseases. Studies with a larger number of patients are needed to fully confirm this hypothesis.


2021 ◽  
Vol 67 (5) ◽  
pp. 427-433
Author(s):  
O.S. Melnichnikova ◽  
I.A. Nazarova ◽  
O.V. Sirotkina ◽  
A.V. Panov ◽  
I.T. Abesadze ◽  
...  

Despite the fact that acetylsalicylic acid (ASA) is the “gold” standard for the prevention of cardiovascular complications in patients with coronary heart disease (CAD), a number of patients still have risks of atherothrombosis. In the present study, the antithrombotic effect of ASA in patients with CAD was assessed in platelet-rich plasma (PRP) using integral tests of the hemostasis study: the T-TAS system (Total Thrombus-formation Analysis System) and the thrombin generation test (TGT). The study involved 34 patients with stable CAD (11 women, 23 men) and people (15 women, 18 men) in the control group. As a result of assessing the activity of thrombus formation using the T-TAS system, a significant decrease in the area under the curve (AUC10) was found in the group with CAD patients compared with the control (135.6 [88.0-222.3] and 260.5 [217.3-301.9], respectively, p


2019 ◽  
Vol 15 (28) ◽  
pp. 3233-3242
Author(s):  
Aijie Li ◽  
Kewen He ◽  
Dong Guo ◽  
Chao Liu ◽  
Duoying Wang ◽  
...  

Aim: To evaluate the value of pretreatment blood biomarkers in predicting pathologic responses to neoadjuvant chemoradiotherapy (neo-CRT) in patients with locally advanced rectal cancer. Materials & methods: We conducted logistic regression analysis and receiver operating characteristic to assess the predictive value of blood biomarkers. The outcome was defined by the pathologic complete response and good response. Results: Carcinoembryonic antigen (CEA) (p < 0.001), neutrophil-to-lymphocyte ratio (p = 0.024), platelet-to-lymphocyte ratio (p = 0.006) and lymphocyte-to-monocyte ratio (LMR) (p < 0.001) were significant predictors of pathologic complete response, with area under the curve of 0.785, 0.794, 0.740 and 0.913, respectively; CEA (p = 0.007) and LMR (p < 0.001) correlated significantly with good response, with area under the curve of 0.743 and 0.771, respectively. Conclusion: Lower LMR and higher CEA, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio before treatment could predict poorer pathologic response to neo-CRT in patients with locally advanced rectal cancer.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Gheyath Al Gawwam ◽  
Inas K. Sharquie

One neurotransmitter, glutamate, has been implicated in the autoimmune demyelination seen in multiple sclerosis (MS). Glutamate is present in many tissues in the body, so consideration should be given to whether the serum level of glutamate is likely well correlated with the activity of the disease. This research aimed to compare the serum glutamate levels from patients diagnosed with MS with those from an age-matched control population. A review of this data could shed light upon whether the serum testing of glutamate using Enzyme-Linked Immunosorbent Assay (ELISA) is a reliable indicator of MS activity. Serum samples were obtained from 55 patients with different patterns of MS and from 25 healthy adults as a control group. The ELISA technique was used to determine the glutamate levels in the serum samples. The mean serum glutamate level for patients with MS was1.318±0.543 nmol/ml and that of the controls was0.873±0.341 nmol/ml. The serum glutamate levels showed an area under the curve via the receiver operating characteristics (ROC) of 0.738, which was significant (pvalue = 0.001). The present study is the first to establish a strong connection between the serum glutamate levels and MS patients, where there was statistically significant elevation of serum glutamate in MS patients; hence this elevation might be used as a monitor to help in the diagnosis of MS patients.


Rheumatology ◽  
2019 ◽  
Vol 58 (9) ◽  
pp. 1655-1661 ◽  
Author(s):  
Michaelin Richards ◽  
Ignacio García-De La Torre ◽  
Yelitza C. González-Bello ◽  
Mónica Vázquez-Del Mercado ◽  
Lilia Andrade-Ortega ◽  
...  

Abstract Objectives The objective of this study was to compare the results obtained from different assays for the detection of anti-Mi-2 antibodies, which are important markers in the diagnosis of DM. Methods The study included 82 patients (68 females/14 males), most of whom had DM (n = 57), followed by PM (n = 16) and juvenile DM (n = 9). All samples were tested using a novel particle-based multi-analyte technology (PMAT) (Inova Diagnostics, research use only) in parallel with a line immunoassay (LIA: Euroimmun). To assess clinical specificity for the PMAT assay, a total of 775 disease and healthy controls were tested. Results 29 samples were positive by at least one test for anti-Mi-2 antibodies. Of those, 24 were Mi-2β LIA+, five were Mi-2α LIA+ and 23 Mi-2 PMAT+. The comparison shows varying agreement between the different methods (kappa 0.27–0.77). When LIA results were used as reference for receiver operating characteristics analysis, high area under the curve values were found for both PMAT vs LIA Mi-2α and LIA Mi-2β. When analysing the results in the context of the myositis phenotype, PMAT associated closest with the DM phenotype. In the control group, 3/775 controls (all low levels) were anti-Mi-2+ resulting in a sensitivity and specificity of 28.1% and 99.6%, respectively. Conclusion Overall, good agreement was found between LIA and PMAT for anti-Mi-2 antibodies, which is important for the standardization of autoantibodies. Anti-Mi-2β antibodies measured by PMAT tend be more highly associated with the clinical phenotype of DM.


2020 ◽  
Vol 27 (1) ◽  
pp. 107327482096944
Author(s):  
Leila T. Tchelebi ◽  
Paul B. Romesser ◽  
Sebastian Feuerlein ◽  
Sarah Hoffe ◽  
Kujtim Latifi ◽  
...  

Colorectal cancer is the third most common cancer in men and the second most common in women worldwide, and the incidence is increasing among younger patients. 30% of these malignancies arise in the rectum. Patients with rectal cancer have historically been managed with preoperative radiation, followed by radical surgery, and adjuvant chemotherapy, with permanent colostomies in up to 20% of patients. Beginning in the early 2000s, non-operative management (NOM) of rectal cancer emerged as a viable alternative to radical surgery in select patients. Efforts have been ongoing to optimize neoadjuvant therapy for rectal cancer, thereby increasing the number of patients potentially eligible to forgo radical surgery. Magnetic resonance guided radiotherapy (MRgRT) has recently emerged as a treatment modality capable of intensifying preoperative radiation therapy for rectal cancer patients. This technology may also predict which patients will achieve a complete response to preoperative therapy, thereby allowing for more appropriate selection of patients for NOM. The present work seeks to illustrate the potential role MRgRT could play in personalizing rectal cancer treatment thus expanding the role of NOM in rectal cancer.


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