pRb2/p130 protein in relation to clinicopathological and biological variables in rectal cancers with a clinical trial of preoperative radiotherapy

2009 ◽  
Vol 24 (11) ◽  
pp. 1303-1310 ◽  
Author(s):  
Satish Babu Moparthi ◽  
Viveka Bergman ◽  
Gunnar Adell ◽  
Sten Thorstensson ◽  
Xiao-Feng Sun
2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15102-e15102
Author(s):  
Chao-Jie Wang ◽  
Jian-Wei Zhou ◽  
Yun Zhou ◽  
Xiao-Feng Sun

e15102 Background:FBI-1 is a recently characterized proto-oncoprotein of the POZ domain Krüppel-like (POK) family of transcription factors. Although several studies provide the evidence that FBI-1 is an important gene regulator in CRC, no analysis of any correlation between FBI-1 expression and preoperative radiotherapy (RT) has been studied in rectal cancers. Methods: This study included the patients with rectal cancer that participated in a Swedish clinical trial of preoperative RT between 1987 and 1990. Patients were divided into preoperative RT (62) and non-RT (77) groups. Applying immunohistochemstry, we detected FBI-1 expression in 118 normal mucosa, 139 primary rectal cancers, and 45 lymph node metastases, and analyzed its relationship with clinicopathological features and RT response. Results: FBI-1 was detected both in the cytoplasm and nucleus, and the cytoplasmic staining was up-regulated compared with normal mucosa both in non-RT and RT groups (74.0% vs. 17.7%, p < 0.001; 69.4% vs. 41.1%, p = 0.002), however, the nuclear staining was down-regulated compared with normal mucosa both in non-RT and RT groups (22.1% vs. 75.8%, p < 0.001; 35.5% vs. 83.9% p < 0.001). Both cytoplasmic and nuclear staining were no difference between the non-RT and RT groups (74.0% vs. 69.4%, p = 0.542; 22.1% vs. 35.5%, p = 0.080, respectively). So we combined the non-RT and RT group together for further analysis. Nuclear staining of FBI-1 was positively with TNM stage and distance recurrence, it showed higher expression in III+ IV stage than that in I+II stage (41.0% vs. 17.9%, p = 0.003). The patients with distance recurrence showed higher FBI-1 expression than that with no distance recurrence (39.7% vs. 19.8%, p = 0.010). In stage I, II and III patients, higher nuclear FBI-1 in primary cancer showed worse disease free survival (HR: 1.934; 95%CI: 1.055-3.579, p = 0.033) and overall survival (HR: 2.174; 95%CI: 1.102-4.290; p = 0.025) independent of gender, age, growth pattern, differentiation and RT. Conclusions: Higher nuclear FBI-1 is related with later TNM stage, distance recurrence, and worse prognosis, it can be used as a potential diagnostic and prognostic biomarker in rectal cancer.


1992 ◽  
Vol 24 (2) ◽  
pp. 108-113 ◽  
Author(s):  
S.J. Arnott ◽  
W. Duncan ◽  
G.R. Kerr ◽  
P.R. Walbaum ◽  
E. Cameron ◽  
...  

2014 ◽  
Vol 40 (11) ◽  
pp. S111
Author(s):  
S. Ionescu ◽  
E. Bratucu ◽  
B. Andreescu ◽  
A. Haidar ◽  
S. Zurac ◽  
...  

2006 ◽  
Vol 24 (28) ◽  
pp. 4620-4625 ◽  
Author(s):  
Jean-Pierre Gérard ◽  
Thierry Conroy ◽  
Franck Bonnetain ◽  
Olivier Bouché ◽  
Olivier Chapet ◽  
...  

Purpose In 1992, preoperative radiotherapy was considered in France as the standard treatment for T3-4 rectal cancers. The present randomized trial compares preoperative radiotherapy with chemoradiotherapy. Patients and Methods Patients were eligible if they presented a resectable T3-4, Nx, M0 rectal adenocarcinoma accessible to digital rectal examination. Preoperative radiotherapy with 45 Gy in 25 fractions during 5 weeks was delivered. Concurrent chemotherapy with fluorouracil 350 mg/m2/d during 5 days, together with leucovorin, was administered during the first and fifth week in the experimental arm. Surgery was planned 3 to 10 weeks after the end of radiotherapy. All patients should receive adjuvant chemotherapy with the same fluorouracil/leucovorin regimen. The primary end point of the trial was overall survival. Results A total of 733 patients were eligible. Grade 3 or 4 acute toxicity was more frequent with chemoradiotherapy (14.6% v 2.7%; P < .05). There was no difference in sphincter preservation. Complete sterilization of the operative specimen was more frequent with chemoradiotherapy (11.4% v 3.6%; P < .05). The 5-year incidence of local recurrence was lower with chemoradiotherapy (8.1% v 16.5%; P < .05). Overall 5-year survival in the two groups did not differ. Conclusion Preoperative chemoradiotherapy despite a moderate increase in acute toxicity and no impact on overall survival significantly improves local control and is recommended for T3-4, N0-2, M0 adenocarcinoma of the middle and distal rectum.


Oncology ◽  
2006 ◽  
Vol 71 (3-4) ◽  
pp. 259-265 ◽  
Author(s):  
Zhi-Yong Zhang ◽  
Zeng-Ren Zhao ◽  
Gunnar Adell ◽  
Ingvar Jarlsfelt ◽  
Yong-Xing Cui ◽  
...  

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3283-3283 ◽  
Author(s):  
Beatriz Sanchez-Vega ◽  
Rafael Alonso ◽  
Isabel Cuenca ◽  
Santiago Barrio ◽  
Yanira Ruiz-Heredia ◽  
...  

Abstract INTRODUCTION Minimal residual disease (MRD) assessment is an essential prognosis factor in multiple myeloma (MM). In this way different high-sensitivity quantification methods are being developed and improved using molecular or flow-cytometry approaches. Currently, the only method available to study molecular response by NGS in MM is clonoSEQ; this is offered as external service by Adaptative Technologies. We have optimized a simplified method to quantify molecular response using NGS. In this work, we compare results when quantifying molecular response by our simplified NGS method or by clonoSEQ. Also we study the prognostic impact of molecular response assessed by NGS techniques in a large series of 181 cases. METHODS We evaluated the molecular response in 71 patients included in GEM2010MAS65 clinical trial by our simplified method, and in 110 patients included in GEM2005 clinical trial by clonoSEQ. Immunoglobulin clonotype quantification by our simplified method: DNA was amplified in accordance with the terms of BIOMED-2 Concerted Action BMH4-CT98-3936. Standard kits were used to prepare libraries (Life Technologies or New England Biolabs), and sequencing was performed with Ion Torrent™ PGM, Ion S5, or MiSeq systems. The resulting FASTQ were analyzed with specific bioinformatic applications in order to identify and quantify clonal specific sequences (clonotype) present in every proband. RESULTS MRD negativity showed significant longer Progression Free Survival (PFS), regardless of the method employed (median 34 months for local method and 32 months for clonoSEQ method in MRD+ patients (MRD>10-5) vs median not reached and 81 months in MRD- patients, respectively, p=0.0001). Likewise, significant differences were observed in terms of Overall Survival (OS) between patients with MRD+ (median 81 months for local method vs 50 months for clonoSEQ method) and MRD- patients (median not reached for both methods), p=0.014. No significant differences were observed in OS and PFS between both local and clonoSEQ NGS techniques (Figure 1). Then, we performed a global analysis with all patients to assess the potential of molecular response evaluated by any NGS method to predict survival regardless of treatment, Molecular response by SEQ was achieved in 43 cases out of 181 (23.7%). Median PFS were 34 vs 80 months for MRD+ and MRD- patients, respectively (p<0.0001, HR=2.8). Median OS were not reached in MRD- patients vs 81 months in MRD+ patients (p=0.004, HR=2.78) (Figure 2). Regression analysis did not show association between any biological variable and MRD- achievement by NGS. When analyzing MRD- patients, no significant differences in PFS or OS were detected between high or standard-risk cytogenetics cases, comparing to differences observed in overall series or in the MRD+ patients group. CONCLUSION Molecular response assessed by NGS is able to identify patients with higher risk, independently of the treatment administered and the method employed. MRD negativity achievement by NGS is an independent risk factor to other clinical and biological variables. Our simplified NGS method offers molecular response information with prognostic value similar to standardized molecular techniques. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Paiva: Celgene: Honoraria, Research Funding; Janssen: Honoraria; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; EngMab: Research Funding; Amgen: Honoraria; Binding Site: Research Funding. Martínez-López:Novartis: Honoraria, Speakers Bureau.


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