scholarly journals Prognostic Significance of DR-70 Levels in Dysplastic Colorectal Polyps

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Atakan Yesil ◽  
Gul Babacan Abanonu ◽  
Yasar Colak ◽  
Nurcan Paker ◽  
Can Gonen
Keyword(s):  
Prognostic Significance ◽  
Serum Levels ◽  
Colorectal Polyps ◽  
Adenomatous Polyps ◽  
Control Group ◽  
Low Grade ◽  
Colon Polyps ◽  
High Grade ◽  
Polyp Size ◽  
Potential Marker

Background. To investigate the relationship between DR-70 serum levels and dysplastic colon polyps.Materials and Methods. A total of 130 patients with adenomatous polyps detected by colonoscopy and divided into two groups including low versus high grade polyp, along with 50 healthy blood donors were included in the study. Blood samples from each participant were analyzed for serum CEA and DR-70 levels.Results. No statistically significant differences were observed between the two groups in terms of age or gender. The median DR-70 level was 0.5 μg/mL in the healthy control group and 1.1 μg/mL in group 1b (i.e., the high grade polyp) (P<0.001). DR-70 was higher in group 1b as compared to group 1a (P<0.001). However, the median DR-70 values for the low grade polyp group (i.e., group 1a) and the control group were similar (P=0.067). In order to determine independent predictors of high grade dysplasia, CEA, DR-70, polyp size, and age parameters were subjected to multiple logistical regression analyses via the Enter method; the model was statistically significant (P<0.001).Conclusions. DR-70, a marker used to measure FDP, which is generated by all major cancers, is a potential marker to identify patients with advanced adenomatous polyps, that is, precursors of colorectal cancer.

scholarly journals Mitochondrial Respiration in KRAS and BRAF Mutated Colorectal Tumors and Polyps

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 815 ◽  
Author(s):  
Egle Rebane-Klemm ◽  
Laura Truu ◽  
Leenu Reinsalu ◽  
Marju Puurand ◽  
Igor Shevchuk ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Atp Synthesis ◽  
Colorectal Polyps ◽  
Metabolic Phenotype ◽  
Mitochondrial Outer Membrane ◽  
Control Group ◽  
Colon Polyps ◽  
Wild Type ◽  
Tissue Samples ◽  
Potential Component

This study aimed to characterize the ATP-synthesis by oxidative phosphorylation in colorectal cancer (CRC) and premalignant colon polyps in relation to molecular biomarkers KRAS and BRAF. This prospective study included 48 patients. Resected colorectal polyps and postoperative CRC tissue with adjacent normal tissue (control) were collected. Patients with polyps and CRC were divided into three molecular groups: KRAS mutated, BRAF mutated and KRAS/BRAF wild-type. Mitochondrial respiration in permeabilized tissue samples was observed using high resolution respirometry. ADP-activated respiration rate (Vmax) and an apparent affinity of mitochondria to ADP, which is related to mitochondrial outer membrane (MOM) permeability, were determined. Clear differences were present between molecular groups. KRAS mutated CRC group had lower Vmax values compared to wild-type; however, the Vmax value was higher than in the control group, while MOM permeability did not change. This suggests that KRAS mutation status might be involved in acquiring oxidative phenotype. KRAS mutated polyps had higher Vmax values and elevated MOM permeability as compared to the control. BRAF mutated CRC and polyps had reduced respiration and altered MOM permeability, indicating a glycolytic phenotype. To conclude, prognostic biomarkers KRAS and BRAF are likely related to the metabolic phenotype in CRC and polyps. Assessment of the tumor mitochondrial ATP synthesis could be a potential component of patient risk stratification.

scholarly journals Abnormal colposcopic images in patients with preinvasive cervical lesions

2013 ◽  
Vol 3 (2) ◽  
pp. 98-102
Author(s):  
Adnan Babović ◽  
Dženita Ljuca ◽  
Gordana Bogdanović ◽  
Lejla Muminhodžić
Keyword(s):  
Intraepithelial Neoplasia ◽  
Control Group ◽  
Low Grade ◽  
High Grade ◽  
Cervical Lesions ◽  
Cytological Examination ◽  
Chi Square ◽  
Chi Square Test ◽  
Intraepithelial Lesion ◽  
Experimental Group

Introduction: The objective of the study was to determine frequency and to compare frequency of the abnormal colposcopic images in patients with low and high grade pre-invasive lesions of cervix.Methods: Study includes 259 patients, whom colposcopic and cytological examination of cervix was done. The experimental group of patients consisted of patents with pre-invasive low grade squamousintraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL), and the control group consisted of patients without cervical intraepithelial neoplasia (CIN).Results: In comparison to the total number of satisfactory fi ndings (N=259), pathological findings were registered in N=113 (43.6 %) and abnormal colposcopic fi ndings in N=128 (49.4%). The study did notinclude patients with unsatisfactory fi nding N=22 (8.5%). Abnormal colposcopic image is present most frequently in older patients but there are no statistically important difference between age categories(Pearson Chi-Square 0.47, df -3, p=0.923). Frequency of abnormal colposcopic fi ndings (N=128) is the biggest in pathological cytological (N=113) and HSIL 58 (45.3%), LSIL 36 (28.1%). There is statisticallysignifi cant difference in frequency of abnormal colposcopic images in patients with low-grade in comparison to patients with high-grade pre-invasive cervix lesions (Chi-Square test, Pearson Chi-Square 117.14,df-12 p<0.0001).Conclusion: Thanks to characteristic colposcopic images, abnormal epithelium is successfully recognized, but the severity grade of intraepithelial lesion cannot be determined.

scholarly journals Subclonal diversity arises early even in small colorectal tumours and contributes to differential growth fates

Gut ◽  
2016 ◽  
Vol 66 (12) ◽  
pp. 2132-2140 ◽  
Author(s):  
Chelsie K Sievers ◽  
Luli S Zou ◽  
Perry J Pickhardt ◽  
Kristina A Matkowskyj ◽  
Dawn M Albrecht ◽  
...  
Keyword(s):  
Computer Modelling ◽  
Clonal Evolution ◽  
Colorectal Polyps ◽  
Colon Polyps ◽  
Growth Behaviour ◽  
Differential Growth ◽  
Polyp Size ◽  
Driver Genes ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Mutations

Objective and designThe goal of the study was to determine whether the mutational profile of early colorectal polyps correlated with growth behaviour. The growth of small polyps (6–9 mm) that were first identified during routine screening of patients was monitored over time by interval imaging with CT colonography. Mutations in these lesions with known growth rates were identified by targeted next-generation sequencing. The timing of mutational events was estimated using computer modelling and statistical inference considering several parameters including allele frequency and fitness.ResultsThe mutational landscape of small polyps is varied both within individual polyps and among the group as a whole but no single alteration was correlated with growth behaviour. Polyps carried 0–3 pathogenic mutations with the most frequent being inAPC,KRAS/NRAS,BRAF,FBXW7andTP53. In polyps with two or more pathogenic mutations, allele frequencies were often variable, indicating the presence of multiple populations within a single tumour. Based on computer modelling, detectable mutations occurred at a mean polyp size of 30±35 crypts, well before the tumour is of a clinically detectable size.ConclusionsThese data indicate that small colon polyps can have multiple pathogenic mutations in crucial driver genes that arise early in the existence of a tumour. Understanding the molecular pathway of tumourigenesis and clonal evolution in polyps that are at risk for progressing to invasive cancers will allow us to begin to better predict which polyps are more likely to progress into adenocarcinomas and which patients are at greater risk of developing advanced disease.

Characterization of CXCR4 Expression in Chondrosarcoma of Bone

2011 ◽  
Vol 135 (6) ◽  
pp. 753-758 ◽  
Author(s):  
Shuting Bai ◽  
Dezhi Wang ◽  
Michael J. Klein ◽  
Gene P. Siegal
Keyword(s):  
Ductal Carcinoma ◽  
Staining Intensity ◽  
The United States ◽  
Cxcr4 Expression ◽  
Low Grade ◽  
High Grade ◽  
Neoplastic Progression ◽  
Regional Lymph Nodes ◽  
Expression Levels ◽  
Potential Marker

Abstract Context.—Alterations in molecular elements derived from the CXC chemokine receptor 4 (CXCR4)/stromal-derived factor 1 (SDF-1) cytokine system have been found to strongly correlate with neoplastic progression leading to metastasis in a number of tumors, including osteosarcoma. Excluding hematologic malignancies, chondrosarcoma of bone is the most common primary malignant tumor of bone in adults in the United States. Like osteosarcoma, chondrosarcoma preferentially metastasizes to lung, bone, and very rarely to regional lymph nodes. However, the role of the signal pathway(s) driving neoplastic progression in chondrosarcoma has not yet been clearly elucidated. Objective.—To test whether CXCR4 was detectable in chondrosarcoma and whether CXCR4 expression levels correlated with chondrosarcoma grade. Design.—Twenty-two chondrosarcoma samples banked at our institution between 2001 and 2006 were retrieved for study. By using invasive ductal carcinoma of the breast and osteosarcoma as the positive controls, immunohistochemistry was performed on paraffin-embedded tissue sections and the intensity of the tumor cells was analyzed by morphometric techniques. Results.—All chondrosarcoma cases (22 of 22) were immunoreactive for CXCR4. However, the staining intensity of the CXCR4 between the low- and high-grade groups was significantly different. There was a higher staining intensity in high-grade chondrosarcoma cells (P &lt; .001). Conclusion.—CXCR4 is expressed in chondrosarcomas. CXCR4 expression levels were higher in high-grade chondrosarcoma cells than in low-grade specimens. A larger number of cases will be required to confirm these results and expand the observation, but preliminary data would argue for CXCR4 immunohistochemistry as a potential marker for biologic aggressiveness in chondrosarcoma of bone.

scholarly journals MISMATCH REPAIR PROTEINS AND SURVIVIN IN ADENOMATOUS COLON POLYPS WITH LOW GRADE AND HIGH GRADE DYSPLASIA: AN IMMUNOHISTOCHEMICAL STUDY. Las proteínas para la reparación de desajustes y survivin en pólipos adenomatosos de colon con displasias de bajo y a

2018 ◽  
Vol 10 (3) ◽  
pp. 98-111
Author(s):  
Marian Adamkov ◽  
Desanka Výbohová ◽  
Slávka Drahošová ◽  
Štefan Galbavý
Keyword(s):  
Mismatch Repair ◽  
Survivin Expression ◽  
High Grade Dysplasia ◽  
Low Grade ◽  
Colon Polyps ◽  
High Grade ◽  
Immunohistochemical Expression ◽  
Significant Relation ◽  
Colon Adenomas ◽  
Mismatch Repair Proteins

Objective: The aim of our study was to observe the immunohistochemical expression pattern of mismatch repair proteins (MMRP) MLH1, MSH2, MSH6 and PMS2, as well as survivin, in colon polyps. Methods: We assessed above mentioned proteins in a unified group of 124 tubular adenomatous colon polyps with regard to the presence of dysplastic abnormalities in order to explore their relationship. Furthermore, we studied their relation to such clinicomorphological parameters as the age of patients, size of adenoma, degree of dysplastic changes and localization of the lesion. Results: Survivin was expressed in 97 cases (78.2%), MLH1 was found in 111 cases (89.5%), MSH2 in 115 cases (92.7%), MSH6 in 118 cases (95.2%) and PMS2 in 105 cases (84.7%). The majority of absent MMRP cases was detected where the adenoma size was less than 10 mm with LGD (low-grade dysplasia). Survivin expression significantly correlated with the adenoma size and dysplasia grade. Subcellular survivin compartmentalization was statistically associated with the adenoma size, dysplasia grade and adenoma localization. Furthermore, we confirmed a significant relation between survivin expression and MMRP. In general, the intensity of immunoreaction was stronger in the MMRP than in survivin. Conclusions: Our recent results suggest that MMRP may suppress the antiapoptotic activity of survivin in LGD and HGD (high grade dysplasia) colon adenomas. Antecedentes: Las proteínas de reparación de desajustes (MMRP) y survivin representan señales diametralmente opuestas que pueden controlar las vías apoptóticas. Además, se sabe que tanto MMRP como survivin son poderosos parámetros pronósticos. Material y métodos: El objetivo de nuestro estudio fue observar el patrón de expresión inmunohistoquímica de MMRP MLH1, MSH2, MSH6 y PMS2, y survivin en un grupo unificado de 124 adenomatosos pólipos tubulares de colon con respecto a la presencia de anomalías displásicas para explorar sus relaciones. Además, estudiamos su relación con los parámetros clinicomorfológicos, como la edad de los pacientes, el tamaño del adenoma, el grado de cambios displásicos y la localización de la lesión. Resultados: Survivin se expresó en 97 casos (78.2%), MLH1 se encontró en 111 casos (89.5%), MSH2 en 115 casos (92.7%), MSH6 en 118 casos (95.2%) y PMS2 en 105 casos (84.7%). La mayoría de los casos ausentes de MMRP se detectaron en un tamaño de adenoma inferior a 10 mm, estos casos se asociaron principalmente con displasia de bajo grado y fueron más frecuentes en el colon distal. La expresión de survivin se correlacionó significativamente con el tamaño del adenoma y el grado de displasia. La compartimentalización de survivin subcelular se asoció estadísticamente con el tamaño del adenoma, el grado de displasia y localización del adenoma. Además, confirmamos una relación significativa entre la expresión de survivin y el MMRP. En general, la intensidad de la inmunorreacción fue más fuerte en MMRP en comparación con la intensidad del survivin. Conclusiones: Con base en nuestros resultados recientes, sugerimos que el MMRP puede suprimir la actividad antiapoptótica del survivin en los adenomas de colon con displasias de bajo y alto grado.

scholarly journals Vitamin e-loaded membrane dialyzers reduce hemodialysis inflammaging

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Vincenzo Sepe ◽  
Marilena Gregorini ◽  
Teresa Rampino ◽  
Pasquale Esposito ◽  
Rosanna Coppo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vitamin E ◽  
Serum Levels ◽  
Hemodialysis Patients ◽  
Control Group ◽  
Low Grade ◽  
Oxide Formation ◽  
Blood Samples ◽  
Indoleamine 2,3 Dioxygenase ◽  
Nitric Oxide Formation

Abstract Background Inflammaging is a persistent, low−grade, sterile, nonresolving inflammatory state, associated with the senescence of the immune system. Such condition downregulates both innate and adaptive immune responses during chronic disorders as type II diabetes, cancer and hemodialysis, accounting for their susceptibility to infections, malignancy and resistance to vaccination. Aim of this study was to investigate hemodialysis inflammaging, by evaluating changes of several hemodialysis treatments on indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation. Methods We conducted a randomized controlled observational crossover trial. Eighteen hemodialysis patients were treated with 3 different hemodialysis procedures respectively: 1) Low−flux bicarbonate hemodialysis, 2) Low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers, and 3) Hemodialfitration. The control group consisted of 14 hospital staff healthy volunteers. Blood samples were collected from all 18 hemodialysis patients just after the long interdialytic interval, at the end of each hemodialysis treatment period. Results Hemodialysis kynurenine and kynurenine/L − tryptophan blood ratio levels were significantly higher, when compared to the control group, indicating an increased indoleamine 2,3-dioxygenase-1 activity in hemodialysis patients. At the end of the low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers period, L − tryptophan serum levels remained unchanged vs both low−flux bicarbonate hemodialysis and hemodialfitration. Kynurenine levels instead decreased, resulting in a significant reduction of kynurenine/L − tryptophan blood ratio and indoleamine 2,3-dioxygenase-1 activity, when matched to both low−flux bicarbonate hemodialysis and HDF respectively. Serum nitric oxide control group levels, were significantly lower when compared to all hemodialysis patient groups. Interestingly, low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers nitric oxide serum levels from venous line blood samples taken 60 min after starting the hemodialysis session were significantly lower vs serum taken simultaneously from the arterial blood line. Conclusions The treatment with more biocompatible hemodialysis procedure as low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers, reduced indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation when compared to both low−flux bicarbonate hemodialysis and hemodialfitration. These data suggest that low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers lowering hemodialysis inflammaging, could be associated to changes of proinflammatory signalling a regulated molecular level. Trial registration NCT Number: NCT02981992; Other Study ID Numbers: 20100014090. First submitted: November 26, 2016. First posted: December 5, 2016. Last Update Posted: December 5, 2016.

Changes in the inflammatory microenvironment in premalignant colonic adenomatous polyps: Evidence for immunosurveillance?

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 535-535
Author(s):  
David Mansouri ◽  
James Hugh Park ◽  
Clare Orange ◽  
Emilia M. Crighton ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
T Cell ◽  
Inflammatory Response ◽  
Adenomatous Polyps ◽  
Observer Agreement ◽  
Cytotoxic T Cell ◽  
Specific Response ◽  
Low Grade ◽  
High Grade ◽  
Early Stage Disease ◽  
Local Inflammatory Response

535 Background: The majority of colorectal cancers develop through the adenoma-carcinoma sequence. Recently, the host inflammatory response has become recognized as a key determinant of outcome. In particular, a pronounced peri-tumoral local inflammatory infiltrate identifies those with a better outcome. The present study aimed to characterize the local inflammatory response in pre-malignant colorectal adenomatous polyps. Methods: Patients with adenomatous polyps removed at colonoscopy as part of a population FOBt screening program were identified from a prospectively maintained database. All polyps were greater than 1cm. Whole slide immunohistochemistry was performed to assess intraepithelial T-cell (CD3+), cytotoxic T-cell (CD8+) and macrophage (CD68+) infiltrate. Inter-observer agreement for assessment of inflammatory cell infiltrate was good or better for CD3+, CD8+ and CD68+staining (Kappa 0.66, 0.66, 0.79 respectively). Results: A total of 207 adenomatous polyps, 107 high-grade (HG), 100 low-grade (LG), from 134 patients were included. Median age was 65 years, 33 (25%) were female and 15 (11%) were taking regular aspirin. Comparing HG and LG polyps, there were more older and female patients in the HG group (p<0.05). There was no difference in location (p=0.222), macroscopic morphology (p=0.445) or aspirin (p=0.377) use between groups. Microscopically, HG polyps were more likely to contain a villous component than LG polyps (65% vs 50%, p<0.05). Overall, high levels of CD3+, CD8+ and CD68+ infiltrate were observed in 68%, 25% and 72% of polyps respectively. Both CD3+ (74% vs 61%, p<0.05) and CD8+ (37% vs 13%, p<0.001) infiltrate was higher in HG polyps compared to LG polyps. There was no association with polyp grade and CD68+infiltrate (74% vs 70%, p=0.540). Conclusions: An increase in local T-lymphocytic infiltrate, but not macrophage infiltrate was identified with progression from low-grade to high-grade dysplasia. This would suggest a specific response to early disease progression confirming increased immunosurveillance. Therefore, such early stage disease may amenable to immunomodulatory treatment.

scholarly journals Predictive Values of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Other Prognostic Factors in Pediatric Patients With Bell’s Palsy

2020 ◽  
pp. 014556132092209 ◽  
Author(s):  
Dong Hyun Kim ◽  
Jae Hwan Oh ◽  
Junsuk Kim ◽  
Chang Hyun Cho ◽  
Ju Hyoung Lee
Keyword(s):  
Prognostic Factors ◽  
Pediatric Patients ◽  
Bell’S Palsy ◽  
Neutrophil To Lymphocyte Ratio ◽  
Control Group ◽  
Low Grade ◽  
High Grade ◽  
Bell's Palsy ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio

Background and Objectives: Bell’s palsy (BP) is the most frequent cause of unilateral facial paralysis, and inflammation is believed to play an important role in pathogenesis. Due to its rarity, however, no consensus has been reached regarding optimum treatment or factors affecting prognosis. In the present study, treatment outcomes and prognostic factors of BP were investigated in pediatric patients who underwent steroid therapy. The goal was to investigate the relationship between BP and inflammation using multiple inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and red cell distribution width (RDW). Materials and Methods: In all, 54 patients diagnosed with BP and 39 healthy randomly selected controls were enrolled in this retrospective study. Demographic characteristics and complete blood cell count test results were compared. In addition, prognostic factors were sought by dividing the 54 patients with BP into 2 groups according to the House-Brackmann grading system: low grade BP (grades II and III) and high grade BP (grades IV and V). Serum samples were analyzed retrospectively on initial presentation and 6 months after the symptom begins. Meaningful hematological parameters include NLR, PLR, MPV, and RDW. Results: The NLR values in the BP group were significantly higher than in the control group. The NLR value in the 2 groups of patients with BP differed significantly. The mean PLR value in the BP group was higher than in the control group; however, there were no significant differences between the low-grade and high-grade BP groups nor were there any statically significant differences in the other characteristics. Conclusion: The NLR and PLR values are readily accessible parameters that may be useful prognostic markers in pediatric patients with BP. Further studies are required to confirm these results and their utility in predicting prognosis and treating pediatric patients with BP.

Chronic Low-Grade Systemic Inflammation in Children with Asthma and Obesity

2018 ◽  
Vol 11 (2) ◽  
pp. 128-134
Author(s):  
Niya A. Krasteva ◽  
Boiko R. Shentov ◽  
Adelaida L. Ruseva ◽  
Chaika K. Petrova ◽  
Simeon P. Petkov
Keyword(s):  
Bronchial Asthma ◽  
Systemic Inflammation ◽  
Inflammatory Markers ◽  
Serum Levels ◽  
Control Group ◽  
Low Grade ◽  
Obese Children ◽  
Asthmatic Children ◽  
Children With Asthma ◽  
Hs Crp

Summary The rising incidence of bronchial asthma and obesity in children raises the question of whether there is a link between them. Chronic low-grade systemic inflammation could be one of the linking mechanisms. We aimed to determine the serum concentrations of high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6) and tumour necrosis factor a (TNF-a) in children with asthma and obesity and to seek a relationship between these inflammatory markers and asthma control. We investigated 88 children aged 6 to 17 years - 25 asthmatic obese children (AsOb), 25 asthmatic non-obese children (AsNOb), 19 obese non-asthmatic children (ObNAs), and 19 non-obese non-asthmatic children as controls. Serum levels of IL-6 and hs-CRP were significantly increased in asthmatic obese and ObNAs compared to AsNOb and the control group. Serum TNF-a concentration was similar in the four studied groups. There were no statistically significant differences in serum levels of these inflammatory markers between controlled and partially controlled/uncontrolled asthmatics (obese and non-obese). Knowing the possible mechanisms of interaction between bronchial asthma and obesity would contribute to a more effective therapeutic approach in these patients.

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