Identification of Helicobacter pylori in tumor biopsies obtained from patients with colorectal cancer: Indication for a prophylactic vaccine?

2021 ◽  
Vol 22 (2) ◽  
pp. 62-67
Author(s):  
N. Kamali ◽  
A. Talebi Bezmin Abadi ◽  
F. Rahimi ◽  
M. Forootan
2021 ◽  
Author(s):  
Yannik Bollen ◽  
Ellen Stelloo ◽  
Petra van Leenen ◽  
Myrna van den Bos ◽  
Bas Ponsioen ◽  
...  

AbstractCentral to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at single-cell resolution. Here, we present 3D Live-Seq—a protocol that integrates live-cell imaging of tumor organoid outgrowth and whole-genome sequencing of each imaged cell to reconstruct evolving tumor cell karyotypes across consecutive cell generations. Using patient-derived colorectal cancer organoids and fresh tumor biopsies, we demonstrate that karyotype alterations of varying complexity are prevalent and can arise within a few cell generations. Sub-chromosomal acentric fragments were prone to replication and collective missegregation across consecutive cell divisions. In contrast, gross genome-wide karyotype alterations were generated in a single erroneous cell division, providing support that aneuploid tumor genomes can evolve via punctuated evolution. Mapping the temporal dynamics and patterns of karyotype diversification in cancer enables reconstructions of evolutionary paths to malignant fitness.


2020 ◽  
Vol 8 (11) ◽  
pp. 1698
Author(s):  
Meira Epplein ◽  
Loïc Le Marchand ◽  
Timothy L. Cover ◽  
Mingyang Song ◽  
William J. Blot ◽  
...  

Previously, we found that risk of colorectal cancer (CRC) is increased in individuals with serum antibody response to both Helicobacter pylori (HP) Vacuolating Cytotoxin (VacA) toxin or Streptococcus gallolyticus (SGG) pilus protein Gallo2178. In the present analysis, we tested the hypothesis that combined seropositivity to both antigens is a better indicator of CRC risk than seropositivity to single antigens. We used multiplex serologic assays to analyze pre-diagnostic serum for antibody responses from 4063 incident CRC cases and 4063 matched controls from 10 US cohorts. To examine whether combined SGG Gallo2178 and HP VacA sero-status was associated with CRC risk, we used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Compared to dual sero-negative individuals, there was no increased risk for individuals sero-positive to SGG Gallo2178 only (OR: 0.93; 95% CI: 0.66–1.31) or to HP VacA only (OR: 1.08; 95% CI: 0.98–1.19). However, dual sero-positive individuals had a >50% increased odds of developing CRC (OR: 1.54; 95% CI: 1.16–2.04), suggesting an interaction between antibody responses to these two pathogens and CRC risk (pinteraction = 0.06). In conclusion, this study suggests that dual sero-positivity to HP VacA and SGG Gallo2178 is an indicator of increased risk of CRC.


2013 ◽  
Vol 22 (11) ◽  
pp. 1964-1974 ◽  
Author(s):  
Meira Epplein ◽  
Michael Pawlita ◽  
Angelika Michel ◽  
Richard M. Peek ◽  
Qiuyin Cai ◽  
...  

1996 ◽  
Vol 14 (3) ◽  
pp. 709-715 ◽  
Author(s):  
J A Conti ◽  
N E Kemeny ◽  
L B Saltz ◽  
Y Huang ◽  
W P Tong ◽  
...  

PURPOSE To determine the response rate, survival, and toxicity of the new anticancer agent, irinotecan (CPT-11), in the treatment of metastatic colorectal cancer. PATIENTS AND METHODS Forty-one chemotherapy-naive patients with measurable metastatic colorectal cancer were treated with a 90-minute infusion of irinotecan 125 mg/m2 administered weekly for 4 weeks every 6 weeks. Pretreatment tumor biopsies to assess topoisomerase-I (Topo-I) activity were obtained from 11 patients. The pharmacokinetics for irinotecan and its active metabolite, SN-38, were determined in 18 patients. RESULTS Thirteen of 41 patients (32%) had a partial response (PR; 95% confidence interval, 18% to 46%). The median response duration was 8.1 months (range, 4.0 to 16.0) and the median survival time was 12.1 months (range, 2.1 to 21.7) for all 41 patients. Grade 3 or 4 toxicities were diarrhea (29% of patients) and neutropenia (22% of patients). Grade 3 or 4 diarrhea was substantially more prevalent in the initial 18 patients on study, with an incidence rate of 56%; a significant reduction in the incidence of severe diarrhea to 9% was noted with strict adherence to an antidiarrheal regimen of loperamide and diphenyldramine. No correlations were seen between pharmacokinetics of irinotecan/SN-38 and the clinical parameters of response, survival, or incidence of diarrhea. CONCLUSIONS Irinotecan has activity in the treatment of patients with metastatic colorectal cancer. Strict adherence to an antidiarrheal regimen of diphenhydramine/loperamide significantly reduced the incidence of diarrhea; the agent was thereafter well tolerated in the majority of patients.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 637-637
Author(s):  
James Hugh Park ◽  
David Mansouri ◽  
Clare Orange ◽  
Paul G. Horgan ◽  
Donald C. Mcmillan ◽  
...  

637 Background: The tumor inflammatory cell infiltrate is an important and potentially modifiable determinant of outcome in colorectal cancer (CRC). Although a weak inflammatory infiltrate is associated with poor prognosis independent of TNM stage, identifying such patients prior to surgery is problematic. The aim of the present study was to compare the tumor inflammatory cell infiltrate in matched preoperative colonoscopic tumor biopsies and resected tumor specimens from patients undergoing primary elective resection of CRC. Methods: Using an automated scoring system (nuclear h-score) CD3+ T-lymphocyte density was quantified in preoperative tumor biopsies of 76 patients undergoing elective resection of stage I-III CRC and compared to pathological characteristics and manual semi-quantitative (high vs. low) scoring of CD3+density within the invasive margin (IM) intraepithelial (IE) and cancer stroma (CS) compartments of resected tumor specimens. Results: The median h-score was 41 (range 14-85). Patients with a high tumor resection IM, IE and CS CD3+ density had a higher biopsy CD3+ density than patients with a low IM, IE and CS CD3+ density (median h-score: IM – 47 vs. 37, p=0.011; IE – 50 vs. 38, p=0.014, CS – 46 vs. 37, p=0.014). Patients with mismatch repair deficient tumors showed a trend towards a higher biopsy CD3+ density (57 vs. 40, p=0.169). No other pathological factors were associated with biopsy CD3+ density. When biopsy CD3+ density was categorised as high (h-score ≥41) or low (h-score<41), high biopsy CD3+ density was associated with CD3+ density within the IM, IE (both p≤0.05) and CS (p<0.01) and showed a trend towards greater 5-year survival (high – 80% (SE 7), low – 67% (SE 8), p=0.122). Conclusions: The results of the present study suggest that assessment of the inflammatory cell infiltrate in preoperative colonoscopic biopsies may provide reliable assessment of the inflammatory cell infiltrate within resected CRC tumors. Although requiring validation in an independent cohort, this has significant implications for the provision of neoadjuvant therapy, particularly targeting the inflammatory cell infiltrate, in patients with primary operable CRC.


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