Evaluation of plasma total and cleaved cytokeratin 18 as predictive markers of chemotherapy in colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15091-e15091
Author(s):  
M. M. Moore ◽  
W. Chua ◽  
J. Zhao ◽  
S. J. Clarke ◽  
L. Horvath

e15091 Background: Cytokeratin 18 (CK18) is a cytoskeletal protein present in the circulation of cancer patients. Caspase-cleaved CK18 fragments are released from apoptotic cells and may be a simple non-invasive tool for measuring response to chemotherapy. This study aims to assess the associations between levels of CK18 with clinical parameters in patients with metastatic colorectal cancer (mCRC) receiving palliative chemotherapy. Methods: Prospectively collected plasma from 23 mCRC patients were analysed for the presence of total CK18 (M65, Peviva) and cleaved CK18 (M30-Apoptosense, Peviva) using an ELISA assay. 8 patients received 2nd-line chemotherapy (irinotecan) and 15 patients received 1st-line 5FU-based chemotherapy. Levels of both total and cleaved CK18 were determined at day 0 prior to chemotherapy and +24 hours for 2nd-line patients or +72 hours for 1st-line patients post-chemotherapy. Patients were grouped as responders (CR + PR) or non-responders (SD + PD) and results were analysed by non-parametric tests (Mann- Whitney and Wilcoxon Signed Rank Tests). Results: The median age of patients was 62 (range 24–79) with 9 patients (39%) responding to chemotherapy. Pre-chemotherapy, both total and cleaved CK18 levels were significantly lower in patients that responded to chemotherapy compared to non-responders [mean total CK18 responders 447.8U/L (95%CI 286.6–609.0 U/L ) versus mean total CK18 non-responders 999.4U/L (95%CI 602.7–1396.1 U/L), p=0.033; mean cleaved CK18 responders 174.7 U/L (95% CI 26.4–323.0) versus mean cleaved CK18 non-responders 331.4 U/L (95%CI 185.3–477.6), p=0.046]. There was a statistically significant increase in the concentration of total CK18 in the post-chemotherapy samples compared to baseline (p=0.003) however there was no association with response (p=0.12). The mean ratio of cleaved: total CK18 was significantly lower after chemotherapy [baseline 0.33 (95% CI 0.28–0.38) versus post-chemotherapy 0.29 (95%CI 0.24–0.34), p=0.01]. The mean ratio of cleaved: total CK18 at baseline was unable to discriminate between responders and non responders (p=0.83). Conclusions: These data suggest that pre-chemotherapy total and cleaved CK18 plasma levels are potential predictors of chemotherapeutic response for patients with mCRC. No significant financial relationships to disclose.

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Grzegorz Słomian ◽  
Elżbieta Świętochowska ◽  
Grzegorz Nowak ◽  
Krystyna Pawlas ◽  
Aleksandra Żelazko ◽  
...  

Adipokines are molecules produced and secreted by adipose tissue and are linked to multiple malignancies. Adipokines can suppress or promote particular cell behaviors in different types of cancer. The aim of this study was to investigate the impact of chemotherapy on select adipokines in patients with colorectal cancer (CRC).Blood samples were collected from 42 patients with pathologically documented advanced CRC, who required palliative chemotherapy. Leptin, adiponectin, resistin and visfatin levels were measured by ELISA before and 3 months after the administration of chemotherapy. Among the 42 patients evaluated, 18 achieved a partial response (PR), 16 achieved stable disease (SD) and 8 patients experienced disease progression (PD).We found that 5-fluorouracil-based chemotherapy regimens significantly increased plasma levels of leptin and adiponectin and decreased plasma levels of resistin and visfatin in PR and SD patients, whereas the plasma levels of these molecules were not affected in PD patients. Furthermore, the mean plasma levels of leptin were significantly lower, and the mean plasma levels of resistin and visfatin were significantly greater in patients with PD compared with PR and SD both before and after chemotherapy treatment.We conclude that palliative chemotherapy in CRC patients, in addition to providing clinical benefits, positively affects cytokine production and secretion in PR and SD patients. Specifically, we found that palliative chemotherapy increased plasma levels of the anti-inflammatory adipokine adiponectin and decreased the plasma levels of visfatin and resistin, molecules known to promote angiogenesis and cancer cell proliferation in PR and SD patients. Moreover, the baseline values of leptin, visfatin and resistin might serve as prognostic indicators of a poor response to chemotherapy.


Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1165
Author(s):  
Kristýna Mezerová ◽  
Lubomír Starý ◽  
Pavel Zbořil ◽  
Ivo Klementa ◽  
Martin Stašek ◽  
...  

The frequent occurrence of E. coli positive for cyclomodulins such as colibactin (CLB), the cytotoxic necrotizing factor (CNF), and the cytolethal distending factor (CDT) in colorectal cancer (CRC) patients published so far provides the opportunity to use them as CRC screening markers. We examined the practicability and performance of a low-cost detection approach that relied on culture followed by simplified DNA extraction and PCR in E. coli isolates recovered from 130 CRC patients and 111 controls. Our results showed a statistically significant association between CRC and the presence of colibactin genes clbB and clbN, the cnf gene, and newly, the hemolytic phenotype of E. coli isolates. We also observed a significant increase in the mean number of morphologically distinct E. coli isolates per patient in the CRC cohort compared to controls, indicating that the cyclomodulin-producing E. coli strains may represent potentially preventable harmful newcomers in CRC patients. A colibactin gene assay showed the highest detection rate (45.4%), and males would benefit from the screening more than females. However, because of the high number of false positives, practical use of this marker must be explored. In our opinion, it may serve as an auxiliary marker to increase the specificity and/or sensitivity of the well-established fecal immunochemical test (FIT) in CRC screening.


Author(s):  
Mina Sameh Sabry ◽  
Amany Emad Eldeen Rady ◽  
Gamal Eldeen Mohamed Niazi ◽  
Susan Adil Ali

Abstract Background The colorectal cancer (CRC) is one of the deadliest cancers in the world. Local tumor stage, vascular or lymphatic invasion, and tumor grade are essential for accurate management. The main imaging modality for initial assessment and therapeutic response evaluation of CRC is magnetic resonance imaging (MRI). The purpose of this prospective study was to illustrate the role of diffusion-weighted MRI (DWI) and apparent diffusion coefficient (ADC) value in initial assessment and grading of colorectal carcinoma as well as evaluation of its response to chemotherapy or combined chemoradiation. Results Restricted diffusion in DWI was found in 37 out of 40 patients with sensitivity of about 92.5%. In the studied group, the median ADC value was 1.21 (min 0.80, max 1.31) and the average ADC value was 1.14 ± 0.161. The mean ADC value in poorly differentiated tumors was 0.979 × 10−3mm2/s. The mean ADC value in moderately differentiated tumors was 1.112 × 10−3mm2/s. The mean ADC value in well-differentiated tumors was 1.273 × 10−3mm2/s. The sensitivity, specificity, PPV, NPV, and accuracy were higher with addition of DWI and ADC value to conventional MRI reaching 100%, 80%, 83.3%, 100%, and 90%, respectively. Conclusion Adding DW imaging with ADC value to conventional MRI yields better diagnostic accuracy than using conventional MR imaging alone in detection, correlation with tumor histologic grade, initial staging, and response evaluation to neoadjuvant chemoradiotherapy in patients with locally advanced colorectal cancer.


Author(s):  
Hend M. Hamdey Rashed Elkalla ◽  
Mohamed Saad Elzahy ◽  
Shoukri Hassan Elazab

Introduction: There was an improvement in therapeutic regimens for advanced colorectal cancer (CRC) in the last few decades. The low dose metronomic palliative chemotherapy in patients with advanced CRC after the failure of standard chemotherapy led to a dramatic increase in efficacy, reduction of mortality rates, and improves survival in the form of control symptoms, and enhances or improves quality of life which is an important issue in that group of patients. Patients and Methods: We include 60 Patients with recurrent or metastatic colorectal cancer after failure of multiple lines of chemotherapy. The patients were randomized in two groups either to receive supportive treatment in group A (30 patients) or low dose weekly leucovorin 20 mg/m² plus 5-flourouracil 425 mg/m² for 3 weeks and 1 week rest in group B (30 patients). Patients in group B received palliative chemotherapy for 4 months at least. Results: After a follow up period of 19 months, the mean time to progression (TTP) is 4.9 months for the group (A) but is higher in group (B) as it is 7.8 months and it shows a statistically significant difference (P value <0.001). Also, the mean overall survival(OS) is 15.3 months for group (A) and 18.8 months for group (B) and this is statistically significant (P value <0.002). No grade 3 or 4 toxicity was detected. After 4 months of the study, 29 patients (96.6%) still have the stable disease compared to 18 patients (60%) of group (A). After 8 months, only 12 patients (40%) of group (B) show stable disease while all patients of group (A) have disease progression. Conclusion: We conclude that metronomic weekly leucovorin-5 FU could provide a good tolerable way to go on with chemotherapy treatment while at the same time not have major threatening side effects.


2019 ◽  
Vol 31 (1) ◽  
Author(s):  
Antonio Francavilla ◽  
Sonia Tarallo ◽  
Barbara Pardini ◽  
Alessio Naccarati

2021 ◽  
Vol 11 (6) ◽  
pp. 513
Author(s):  
Zheng Zhang ◽  
Meng Gu ◽  
Zhongze Gu ◽  
Yan-Ru Lou

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.


Author(s):  
Patrick Veit-Haibach ◽  
Martin W. Huellner ◽  
Martin Banyai ◽  
Sebastian Mafeld ◽  
Johannes Heverhagen ◽  
...  

Abstract Objectives The purpose of this study was the assessment of volumetric CT perfusion (CTP) of the lower leg musculature in patients with symptomatic peripheral arterial disease (PAD) before and after interventional revascularisation. Methods Twenty-nine consecutive patients with symptomatic PAD of the lower extremities requiring interventional revascularisation were assessed prospectively. All patients underwent a CTP scan of the lower leg, and hemodynamic and angiographic assessment, before and after intervention. Ankle-brachial pressure index (ABI) was determined. CTP parameters were calculated with a perfusion software, acting on a no outflow assumption. A sequential two-compartment model was used. Differences in CTP parameters were assessed with non-parametric tests. Results The cohort consisted of 24 subjects with an occlusion, and five with a high-grade stenosis. The mean blood flow before/after (BFpre and BFpost, respectively) was 7.42 ± 2.66 and 10.95 ± 6.64 ml/100 ml*min−1. The mean blood volume before/after (BVpre and BVpost, respectively) was 0.71 ± 0.35 and 1.25 ± 1.07 ml/100 ml. BFpost and BVpost were significantly higher than BFpre and BVpre in the treated limb (p = 0.003 and 0.02, respectively), but not in the untreated limb (p = 0.641 and 0.719, respectively). Conclusions CTP seems feasible for assessing hemodynamic differences in calf muscles before and after revascularisation in patients with symptomatic PAD. We could show that CTP parameters BF and BV are significantly increased after revascularisation of the symptomatic limb. In the future, this quantitative method might serve as a non-invasive method for surveillance and therapy control of patients with peripheral arterial disease. Key Points • CTP imaging of the lower limb in patients with symptomatic PAD seems feasible for assessing hemodynamic differences before and after revascularisation in PAD patients. • This quantitative method might serve as a non-invasive method, for surveillance and therapy control of patients with PAD.


Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1382
Author(s):  
Olga Martyna Koper-Lenkiewicz ◽  
Violetta Dymicka-Piekarska ◽  
Anna Justyna Milewska ◽  
Justyna Zińczuk ◽  
Joanna Kamińska

The aim of the study was the evaluation whether in primary colorectal cancer (CRC) patients (n = 55): age, sex, TNM classification results, WHO grade, tumor location (proximal colon, distal colon, rectum), tumor size, platelet count (PLT), mean platelet volume (MPV), mean platelet component (MCP), levels of carcinoembryonic antigen (CEA), cancer antigen (CA 19-9), as well as soluble lectin adhesion molecules (L-, E-, and P-selectins) may influence circulating inflammatory biomarkers: IL-6, CRP, and sCD40L. We found that CRP concentration evaluation in routine clinical practice may have an advantage as a prognostic biomarker in CRC patients, as this protein the most comprehensively reflects clinicopathological features of the tumor. Univariate linear regression analysis revealed that in CRC patients: (1) with an increase in PLT by 10 × 103/μL, the mean concentration of CRP increases by 3.4%; (2) with an increase in CA 19-9 of 1 U/mL, the mean concentration of CRP increases by 0.7%; (3) with the WHO 2 grade, the mean CRP concentration increases 3.631 times relative to the WHO 1 grade group; (4) with the WHO 3 grade, the mean CRP concentration increases by 4.916 times relative to the WHO 1 grade group; (5) with metastases (T1-4N+M+) the mean CRP concentration increases 4.183 times compared to non-metastatic patients (T1-4N0M0); (6) with a tumor located in the proximal colon, the mean concentration of CRP increases 2.175 times compared to a tumor located in the distal colon; (7) in patients with tumor size > 3 cm, the CRP concentration is about 2 times higher than in patients with tumor size ≤ 3 cm. In the multivariate linear regression model, the variables that influence the mean CRP value in CRC patients included: WHO grade and tumor localization. R2 for the created model equals 0.50, which indicates that this model explains 50% of the variance in the dependent variable. In CRC subjects: (1) with the WHO 2 grade, the mean CRP concentration rises 3.924 times relative to the WHO 1 grade; (2) with the WHO 3 grade, the mean CRP concentration increases 4.721 times in relation to the WHO 1 grade; (3) with a tumor located in the rectum, the mean CRP concentration rises 2.139 times compared to a tumor located in the distal colon; (4) with a tumor located in the proximal colon, the mean concentration of CRP increases 1.998 times compared to the tumor located in the distal colon; if other model parameters are fixed.


2021 ◽  
Vol 28 ◽  
pp. 107327482110099
Author(s):  
Abdosaleh Jafari ◽  
Peyman Mehdi Alamdarloo ◽  
Mehdi Dehghani ◽  
Peivand Bastani ◽  
Ramin Ravangard

Among cancers, colorectal cancer is the third most common cancer in the world and the fourth leading cause of cancer deaths worldwide. Some studies have shown that the incidence of colorectal cancer is increasing in Iran and in Fars province. The present study aimed to determine the economic burden of colorectal cancer in patients referred to the referral centers affiliated to Iran, Shiraz University of Medical Sciences in 2019 from the patients’ perspective. This is a partial economic evaluation and a cost-of-illness study conducted cross-sectionally in 2019. All the patients with colorectal cancer who had been referred to the referral centers affiliated to Iran, Shiraz University of Medical Sciences, and had medical records were studied through the census method (N = 96). A researcher-made data collection form was used to collect the cost data. The prevalence-based and bottom-up approaches were also used in this study. The human capital approach was applied to calculate indirect costs. The mean annual cost per patient with colorectal cancer in the present study was $10930.98 purchasing power parity (PPP) (equivalent to 5745.29 USD), the main part of which was the medical direct costs (74.86%). Also, among the medical direct costs per patient, the highest were those of surgeries (41.7%). In addition, the mean annual cost per patient with colorectal cancer in the country was $ 116917762 PPP (equivalent to 61451621.84 USD) in 2019. Regarding the considerable economic burden of colorectal cancer and in order to reduce the costs, these suggestions can be made: increasing the number of specialized beds through the cooperation of health donors, establishing free or low-cost accommodation centers for patients and their companions near the medical centers, using the Internet and cyberspace technologies to follow up the treatment of patients, and increasing insurance coverage and government drug subsidies on drug purchase.


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