Pharmacokinetics and Clinical Evaluation of125I-Radiolabeled Humanized CC49 Monoclonal Antibody (HuCC49ΔCH2) in Recurrent and Metastatic Colorectal Cancer Patients

2005 ◽  
Vol 20 (1) ◽  
pp. 16-26 ◽  
Author(s):  
Jim Xiao ◽  
Sara Horst ◽  
George Hinkle ◽  
Xianhua Cao ◽  
Ergun Kocak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibody ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Clinical Evaluation ◽  
Colorectal Cancer Patients

Two immunoglobulin G fragment C receptor polymorphisms associated with clinical outcome of EGFR-expressing metastatic colorectal cancer patients treated with single agent cetuximab

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3028-3028 ◽  
Author(s):  
W. Zhang ◽  
M. Gordon ◽  
A. M. Schultheis ◽  
F. Nagashima ◽  
M. Azuma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibody ◽  
Clinical Outcome ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Immunoglobulin G ◽  
Tumor Response ◽  
Single Agent ◽  
Exact Test ◽  
Colorectal Cancer Patients

3028 Background: Cetuximab is a chimeric immunoglobulin G1 anti-EGFR monoclonal antibody with efficacy in metastatic colorectal cancer patients refractory to irinotican chemotherapy. Recent studies show that Antibody-dependent cellular cytotoxicity (ADCC) mediated through Fc receptors plays an important role in the antitumor effect of IgG1 antibody. There are three classes of FcγRs involved in the regulation of ADCC. FcγRIIa(CD32) and FcγRIIIa(CD16) activates and FcγRIIb inhibits activation. Clinical studies show FcγRIIIa 158 V/F polymorphism was associated with tumor response and progression-free survival in the follicular lymphoma patients treated with rituximab as first line treatment. Also, a H/R polymorphism at position 131 of FcγRIIa has been found to affects its affinity to human IgG and independently predict response to Rituximab. Since Cetuximab and Rituximab belong to the same chimeric IgG1 monoclonal antibody, we test hypothesis whether these two FcγR polymorphisms associated with clinical outcome in colorectal cancer patients treated with single agent Cetuximab. Methods: we tested both FcγRIIIa 158 V/F and FcγRIIa 131 H/R gene polymorphisms using PCR-RFLP method in genomic DNA extracted from peripheral blood from 39 EGFR-expressing metastatic colorectal cancer patients enrolled in a phase II single agent Cetuximab treatment clinical trial (IMCL-0144). Results: We found patients with FcγRIIa 131 HH or HR genotype show better time to progression and overall survival compare to patients with R/R genotype (p=0.037, p=0.22, respectively, log-rank test). Also, there is trend significance in tumor response when we compare patients with RR genotype and patients with HH or HR genotype (p=0.08, fisher’s exact test). FcγRIIIa 158 V/F also show trend significance in tumor response (p=0.067, fisher’s exact test). Conclusions: These data suggest Two Immunoglobulin G Fragment C Receptor polymorphismsFcγRIIIa158V/F andFcγRIIa 131 H/R may be potential molecular markers for clinical outcome of refractory metastatic colorectal caner patients treated with single agent EGFR inhibitor Cetuximab. Prospective studies are needed to confirm these preliminary findings. [Table: see text]

scholarly journals Influence of Postoperative Changes in Sarcopenia on Long-Term Survival in Non-Metastatic Colorectal Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2410
Author(s):  
Chungyeop Lee ◽  
In-Ja Park ◽  
Kyung-Won Kim ◽  
Yongbin Shin ◽  
Seok-Byung Lim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Medical Center ◽  
The Body ◽  
Term Survival ◽  
Postoperative Changes ◽  
Asan Medical ◽  
Colorectal Cancer Patients

The effect of perioperative sarcopenic changes on prognosis remains unclear. We conducted a retrospective cohort study with 2333 non-metastatic colorectal cancer patients treated between January 2009 and December 2012 at the Asan Medical Center. The body composition at diagnosis was measured via abdominopelvic computed tomography (CT) using Asan-J software. Patients underwent CT scans preoperatively, as well as at 6 months–1 year and 2–3 years postoperatively. The primary outcome was the association between perioperative sarcopenic changes and survival. According to sarcopenic criteria, 1155 (49.5%), 890 (38.2%), and 893 (38.3%) patients had sarcopenia preoperatively, 6 months–1 year, and 2–3 years postoperatively, respectively. The 5-year overall survival (OS) (95.8% vs. 92.1%, hazard ratio (HR) = 2.234, p < 0.001) and 5-year recurrence-free survival (RFS) (93.2% vs. 86.2%, HR = 2.251, p < 0.001) rates were significantly lower in patients with preoperative sarcopenia. Both OS and RFS were lower in patients with persistent sarcopenia 2–3 years postoperatively than in those who recovered (OS: 96.2% vs. 90.2%, p = 0.001; RFS: 91.1% vs. 83.9%, p = 0.002). In multivariate analysis, postoperative sarcopenia was confirmed as an independent factor associated with decreased OS and RFS. Pre- and postoperative sarcopenia and changes in the condition during surveillance were associated with oncological outcomes.

scholarly journals Small EVs-Associated DNA as Complementary Biomarker to Circulating Tumor DNA in Plasma of Metastatic Colorectal Cancer Patients

2021 ◽  
Vol 14 (2) ◽  
pp. 128
Author(s):  
Silvia Galbiati ◽  
Francesco Damin ◽  
Dario Brambilla ◽  
Lucia Ferraro ◽  
Nadia Soriani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Digital Pcr ◽  
Extracellular Vesicle ◽  
Circulating Tumor Dna ◽  
Mutation Status ◽  
Promising Practice ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

It is widely accepted that assessing circular tumor DNA (ctDNA) in the plasma of cancer patients is a promising practice to evaluate somatic mutations from solid tumors noninvasively. Recently, it was reported that isolation of extracellular vesicles improves the detection of mutant DNA from plasma in metastatic patients; however, no consensus on the presence of dsDNA in exosomes has been reached yet. We analyzed small extracellular vesicle (sEV)-associated DNA of eleven metastatic colorectal cancer (mCRC) patients and compared the results obtained by microarray and droplet digital PCR (ddPCR) to those reported on the ctDNA fraction. We detected the same mutations found in tissue biopsies and ctDNA in all samples but, unexpectedly, in one sample, we found a KRAS mutation that was not identified either in ctDNA or tissue biopsy. Furthermore, to assess the exact location of sEV-associated DNA (outside or inside the vesicle), we treated with DNase I sEVs isolated with three different methodologies. We found that the DNA inside the vesicles is only a small fraction of that surrounding the vesicles. Its amount seems to correlate with the total amount of circulating tumor DNA. The results obtained in our experimental setting suggest that integrating ctDNA and sEV-associated DNA in mCRC patient management could provide a complete real-time assessment of the cancer mutation status.

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