scholarly journals Association between Microsatellite Instability Status and Peri-Operative Release of Circulating Tumour Cells in Colorectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 425 ◽  
Author(s):  
James W. T. Toh ◽  
Stephanie H. Lim ◽  
Scott MacKenzie ◽  
Paul de Souza ◽  
Les Bokey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Venous Blood ◽  
Peripheral Circulation ◽  
Curative Intent ◽  
Mean Values ◽  
Time Points ◽  
Significant Difference ◽  
Circulating Tumour Cell ◽  
Infiltrating Lymphocytes

Microsatellite instability (MSI) in colorectal cancer (CRC) is a marker of immunogenicity and is associated with an increased abundance of tumour infiltrating lymphocytes (TILs). In this subgroup of colorectal cancer, it is unknown if these characteristics translate into a measurable difference in circulating tumour cell (CTC) release into peripheral circulation. This is the first study to compare MSI status with the prevalence of circulating CTCs in the peri-operative colorectal surgery setting. For this purpose, 20 patients who underwent CRC surgery with curative intent were enrolled in the study, and peripheral venous blood was collected at pre- (t1), intra- (t2), immediately post-operative (t3), and 14–16 h post-operative (t4) time points. Of these, one patient was excluded due to insufficient blood sample. CTCs were isolated from 19 patients using the IsofluxTM system, and the data were analysed using the STATA statistical package. CTC number was presented as the mean values, and comparisons were made using the Student t-test. There was a trend toward increased CTC presence in the MSI-high (H) CRC group, but this was not statistically significant. In addition, a Poisson regression was performed adjusting for stage (I-IV). This demonstrated no significant difference between the two MSI groups for pre-operative time point t1. However, time points t2, t3, and t4 were associated with increased CTC presence for MSI-H CRCs. In conclusion, there was a trend toward increased CTC release pre-, intra-, and post-operatively in MSI-H CRCs, but this was only statistically significant intra-operatively. When adjusting for stage, MSI-H was associated with an increase in CTC numbers intra-operatively and post-operatively, but not pre-operatively.

Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic

2004 ◽  
Vol 91 (4) ◽  
pp. 469-475 ◽  
Author(s):  
S. M. Phillips ◽  
A. Banerjea ◽  
R. Feakins ◽  
S. R. Li ◽  
S. A. Bustin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

scholarly journals Cyclin D1 G870A Variant is Associated with Increased Risk of Microsatellite Instability-Positive Colorectal Cancer in Young Male Patients

2007 ◽  
Vol 10 (2) ◽  
pp. 29-36
Author(s):  
T Josifovski ◽  
N Matevska ◽  
M Hiljadnikova-Bajro ◽  
Z Sterjev ◽  
A Kapedanovska ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cyclin D1 ◽  
Regulatory Protein ◽  
Significant Risk ◽  
Young Male ◽  
Genotype Distribution ◽  
Increased Risk ◽  
Significant Difference ◽  
Male Patients

Cyclin D1 G870A Variant is Associated with Increased Risk of Microsatellite Instability-Positive Colorectal Cancer in Young Male PatientsCyclin D1 (CCND1) is a cell cycle regulatory protein, which is often over expressed in human tumors and is associated with cell proliferation and poor prognosis. A common G870A single nucleotide polymorphism at codon 242 in exon 4 of the CCND1 gene is associated with an altered messenger RNA transcript and increased risk of colorectal cancer (CRC) and adenoma in some studies. Over expression of CCND1 modifies the effect of mutations in mismatch repair (MMR) genes, enhances microsatellite instability (MSI), and influences the age ofonset of hereditary non polyposis colorectal cancer (HNPCC). We have extended our study that indicated that the CCND1 A variant may influence the age of onset of CRC in the Macedonian population only in patients who exhibit MSI tumors by a case control study of 331 randomly selected CRC patients and 101 controls without clinical diagnosis of CRC. We did not observe a significant difference in overall allelic frequencies and genotype distribution of affected and unaffected mutation carriers, but found a statistically significant risk of CRC in carriers of the CCND1 A allele when patients were grouped according to gender, age and MSI status. A higher risk was observed in patients with MSI-positive tumors and particularly in male patients under 60 years of age. The consequences of the above observation were reversed in female patients. These results indicate that the CCND1 A variant may enhance CRC progression through a pathway influenced by estrogens in colonic epithelia.

scholarly journals Micronucleus occurrence in diploid and triploid rainbow trout (Oncorhynchus mykiss Walbaum)

2012 ◽  
Vol 48 (No. 8) ◽  
pp. 215-220 ◽  
Author(s):  
I. Strunjak-Perovic ◽  
R. Coz-Rakovac ◽  
N. Topic Popovic
Keyword(s):  
Rainbow Trout ◽  
Oncorhynchus Mykiss ◽  
Water Temperature ◽  
Peripheral Circulation ◽  
Ploidy Levels ◽  
Mean Values ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Significant Difference

The aim of the study was to observe the influence of different ploidy levels in fish on micronucleus occur­rence. Twenty minutes after fertilization, one group of rainbow trout eggs was exposed to water temperatures of 26°C in duration of 20 minutes to induce triploidy. Second group was kept in water temperature of 10°C, which is optimal for development of rainbow trout. The frequency of micronucleated erythrocytes was determined in the peripheral circulation of rainbow trout 67 days (following absorption of the yolk – swim-up stage) and 128 days (fry stage) post fertilization. There was a significant difference (P < 0.001) between frequency of micronucleated erythrocytes of diploid (1.10 ± 0.96‰) and triploid (2.41 ± 1.28‰) fish at swim-up stage. Increased mean values of micronucleus in diploid (1.80 ± 1.57‰) and triploid (5.92 ± 3.80‰) fry were also recorded.

scholarly journals Mutational Analysis of Patients With Colorectal Cancer in CALGB/SWOG 80405 Identifies New Roles of Microsatellite Instability and Tumor Mutational Burden for Patient Outcome

2019 ◽  
Vol 37 (14) ◽  
pp. 1217-1227 ◽  
Author(s):  
Federico Innocenti ◽  
Fang-Shu Ou ◽  
Xueping Qu ◽  
Tyler J. Zemla ◽  
Donna Niedzwiecki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Metastatic Colorectal Cancer ◽  
Mutational Analysis ◽  
Gene Mutations ◽  
Phase Iii ◽  
First Line ◽  
Mutational Burden ◽  
Significant Difference ◽  
Tumor Mutational Burden

PURPOSE CALGB/SWOG 80405 was a randomized phase III trial that found no statistically significant difference in overall survival (OS) in patients with first-line metastatic colorectal cancer treated with chemotherapy plus either bevacizumab or cetuximab. Primary tumor DNA from 843 patients has been used to discover genetic markers of OS. PATIENTS AND METHODS Gene mutations were determined by polymerase chain reaction. Microsatellite status was determined by genotyping of microsatellites. Tumor mutational burden (TMB) was determined by next-generation sequencing. Cox proportional hazard models were used, with adjusting factors. Interaction of molecular alterations with either the bevacizumab or the cetuximab arms was tested. RESULTS Patients with high TMB in their tumors had longer OS than did patients with low TMB (hazard ratio [HR], 0.73 [95% CI, 0.57 to 0.95]; P = .02). In patients with microsatellite instability–high (MSI-H) tumors, longer OS was observed in the bevacizumab arm than in the cetuximab arm (HR, 0.13 [95% CI, 0.06 to 0.30]; interaction P < .001 for interaction between microsatellite status and the two arms). Patients with BRAF mutant tumors had shorter OS than did patients with wild-type (WT) tumors (HR, 2.01 [95% CI, 1.49 to 2.71]; P < .001). Patients with extended RAS mutant tumors had shorter OS than did patients with WT tumors (HR, 1.52 [95% CI, 1.26 to 1.84]; P < .001). Patients with triple-negative tumors (WT for NRAS/ KRAS/ BRAF) had a median OS of 35.9 months (95% CI, 33.0 to 38.8 months) versus 22.2 months (95% CI, 19.6 to 24.4 months ) in patients with at least one mutated gene in their tumors ( P < .001). CONCLUSION In patients with metastatic colorectal cancer treated in first line, low TMB, and BRAF and RAS mutations are negative prognostic factors. Patients with MSI-H tumors benefited more from bevacizumab than from cetuximab, and studies to confirm this effect of MSI-H are warranted.

Acquired Antithrombin III (AT III) - Deficiency in Septicaemia

1979 ◽  
Author(s):  
E. Deutsch ◽  
E. Thaler
Keyword(s):  
Septic Shock ◽  
Venous Blood ◽  
Heparin Therapy ◽  
Blood Cultures ◽  
Mean Values ◽  
Negative Results ◽  
Significant Difference ◽  
At Iii ◽  
Group 2 ◽  
Group 1

AT III was measured in 34 patients with clinical and bacteriological evidence of septicaemia using a heparin cofactor assay. Based on the results of positive blood cultures gram-negative septicaemia (G-S) was diagnosed in 10 (group 1) and gram positive septicaemia (G+S) in 9 patients (group 2). From the remaining 15 patients {group 3) blood cultures before onset of antibiotic therapy were not obtained and gave negative results throughout the observation period. Based on bacteria] cultures from other sites than venous blood or bacteriological examination of spinal fluid G-S was assumed in 13 and G+S in 2 patients.In all but one patient of group 1 and one of group 2 AT III activities were decreased below 2 SO of normal controls (n = 91, x = 99.6, SD-8.4) already at the time of the first coagulation screening (patients: n=34, =58.4, SD-16.6). Analysis of var-ance showed no significant difference between the mean values of the three groups at the c per cent (%) level. The minimal AT III activities during the course of the disease were below the norma] range in all patients studied [n=34, =51.2, SD=13.6).Thus AT III deficiency appears to be a constant and early finding in G-S and G+S, causing insufficient inhibition of blood coagulation, and hereby may contribute to irreversible tissue damage caused by microthrombi in septic shock. This deficiency may be an important factor in the failure of heparin therapy to reduce mortality from septic shock.

scholarly journals THE EFFECT OF COMPREHENSIVE TREATMENT OF PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE IN COMBINATION WITH PREDIABETES ON THE LIPID PROFILE

2021 ◽  
Vol 74 (4) ◽  
pp. 957-960
Author(s):  
Vitalina V. Ivachevska
Keyword(s):  
Physical Activity ◽  
Lipid Profile ◽  
Ursodeoxycholic Acid ◽  
Venous Blood ◽  
Comprehensive Treatment ◽  
Omega 3 ◽  
Alcoholic Fatty Liver ◽  
Mean Values ◽  
Significant Difference ◽  
Venous Blood Sampling

The aim: To evaluate the efficiency of the proposed therapy, which included recommendations for nutrition, physical activity and treatment with rosuvastatin, omega-3 PUFA and ursodeoxycholic acid, on the indicators of the lipid profile in patients with NAFLD and prediabetes. Materials and methods: 78 patients with impaired glucose tolerance were examined. According to the inclusion and exclusion criteria, 55 patients with prediabetes and concomitant NAFLD were included in the study. All patients underwent a comprehensive clinical examination, which included anthropometric data collection, objective examination, and venous blood sampling for laboratory tests. Results: The data obtained after 12 months of proposed treatment revealed a statistically significant improvement of indicators lipid profile in patients with prediabetes and NAFLD. Moreover, no significant difference between mean values of HDLC, LDLC, TG and atherogenic coefficient of almost healthy individuals and the corresponding indicators of treated patients detected. Conclusions: therapy which included recommendations for nutrition, physical activity and treatment with rosuvastatin, omega-3 PUFA and ursodeoxycholic acid significantly improved lipid metabolism in patients with prediabetes and NAFLD.

scholarly journals Prognostic significance of macrosatellite instability in patients under 50 years of age suffering from colorectal cancer

2009 ◽  
Vol 62 (5-6) ◽  
pp. 217-223
Author(s):  
Atila Fenjvesi
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Prognostic Significance ◽  
Young Patients ◽  
Dna Mismatch ◽  
Significant Difference ◽  
Sporadic Cases ◽  
Microsatellite Stability ◽  
Better Than

Introduction Colorectal cancer (CRC) can arise through two distinct mutational pathways: microsatellite instability or chromosomal instability. High-frequency microsatellite instability (MSI) occurs in approximately 15 percent of sporadic cases of CRCs. Many studies have well established that MSI, the hallmark of defective DNA mismatch repair, is associated with prolonged survival of CRC patients compared with tumors that are microsatellite stable. CRCs in patients under 50 years of age are rare and represent about 5% of the total number of tumors. The aim of this study was to analyze the prognostic significance of MSI in CRC patients younger than 50 at the time of diagnosis. Material and methods 31 patients with CRC under 50 years of age were tested for the presence of MSI, and compared with 35 patients aged 50 or more at the time of diagnosis. CRC-specific survival five-year- follow-up period was analyzed in relation to MSI status. Results The frequency of MSI among the young patients was 35.48%, which was significantly higher than the rate of 11.43% noted in older patients with CRCs (p<0.042). This study revealed no difference in survival in patients with CRCs aged less than 50 compared with those over 50 years of age. The five-years survival of young CRCs patients with MSI 81.82%, was better than that of the patients with cancers with microsatellite stability, 60%, but there was no significant difference in statistics. Discussion and conclusion In our study there was no statistically detectable significant difference between tumor microsatellite status and survival in young patients, although we confirmed the previous observations that MSI is associated with better prognosis. We found that the pathological stage of CRC was an independent and powerful predictor of the clinical outcome.

Role of MSI and DCC status to predict response to FOLFOX in metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21056-21056
Author(s):  
M. Bennamoun ◽  
O. Schischmanoff ◽  
A. Martin ◽  
P. Mariani ◽  
L. Ah Koon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Disease Free Survival ◽  
Current Treatment ◽  
Metastatic Colon Cancer ◽  
Significant Difference ◽  
Microsatellite Stability

21056 Background: Microsatellite instability (MSI) and lack of Deleted Colon Cancer (DCC) protein expression have been observed respectively in ∼15% and 70% of colon cancer cases and are considered as prognostic factors in colorectal cancer (CRC). In adjuvant setting these markers could be considered to decide treatment. We know that MSI colon cancer do not benefit from 5Fluorouracyl (5FU)-based chemotherapy. A current treatment of reference for colon cancer is a combination of 5FU and Oxaliplatin (FOLFOX). Our aim was to determine whether MSI status or DCC expression are predictive markers of FOLFOX efficiency in patients with metastatic CRC. Methods: Tumour specimens were collected from patients with metastatic colon cancer treated with FOLFOX. The FOLFOX regimen was evaluated in first line treatment according to the WHO criteria. The microsatellite instability status was assessed by measurement of the length of five monomorphic mononucleotide markers. DCC protein expression were evaluated by immunohistochemistry. Results: Forty patients (22 men, 18 women), median age 63.5 years (27–83) were treated with FOLFOX. Nine patients had tumours exhibiting high microsatellite instability (microsatellite instability group, MSI group) and 31 patients had tumours exhibiting microsatellite stability (microsatellite stable group, MSS group). In MSS group, we observed 11 partial responses (36%) and only two in MSI group (22%) (not significant difference). Both disease free survival and overall survival were not significantly different for MSI and MSS groups. Determination of DCC status is under investigation. Conclusions: There was no significant difference in chemosensitivity to FOLFOX for MSI and MSS metastatic patients. Therefore FOLFOX regimen could be proposed to metastatic patients irrespective of MSI status. The study of the relationship between DCC expression and response to FOLFOX is ongoing. No significant financial relationships to disclose.

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