Modulation of the Cholesterol Pathway During Epithelial-to-Mesenchymal Transition Influences Tumor Molecular Differentiation and Disease-Free Survival in Colon Cancer Patients

Purpose In preclinical models, there is synergism between chemotherapy and recombinant human tumor necrosis factor (TNF) –related apoptosis-inducing ligand (TRAIL) on apoptosis induction in tumor cells. Therefore, the prognostic relevance was analyzed of the expression of TRAIL and its death receptors DR4 and DR5 on disease-free survival and overall survival in stage III colon cancer patients treated with adjuvant chemotherapy. Methods Tissue microarrays were constructed of primary tumor tissue from 376 stage III colon cancer patients treated in a randomized adjuvant chemotherapy study (fluorouracil/levamisole v fluorouracil/levamisole/leucovorin) and stained immunohistochemically for TRAIL, DR4, and DR5. Log-rank tests and Cox proportional hazard analysis, with adjustment for treatment arm, sex, age, N stage, microsatellite instability status, and p53 mutation status, were performed. Results The majority of tumors showed high expression of TRAIL (83%), DR4 (92%), and DR5 (87%). Median follow-up was 43 months. High DR4 expression was associated with worse disease-free survival (odds ratio [OR] = 2.19; 95% CI, 1.06 to 4.53; P = .03), worse overall survival (OR = 2.22; 95% CI,1.03 to 4.81; P = .04) and shorter time to recurrence (P = .02) compared with those with low DR4 expression. TRAIL or DR5 expression had no prognostic value. Conclusion High DR4 expression is associated with worse disease-free and overall survival in stage III adjuvant-treated colon cancer patients. Evaluation of DR4 expression in stage III colon cancer patients may identify a subset requiring more aggressive adjuvant treatment.

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Epithelial to Mesenchymal Transition is Associated with Shorter Disease-Free Survival in Hepatocellular Carcinoma

Annals of Surgical Oncology ◽

10.1245/s10434-014-3779-2 ◽

2014 ◽

Vol 21 (12) ◽

pp. 3882-3890 ◽

Cited By ~ 41

Author(s):

Suguru Yamada ◽

Norio Okumura ◽

Lan Wei ◽

Bryan C. Fuchs ◽

Tsutomu Fujii ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial To Mesenchymal Transition ◽

Disease Free Survival ◽

Free Survival ◽

Mesenchymal Transition ◽

Disease Free

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Defective Mismatch Repair Status as a Prognostic Biomarker of Disease-Free Survival in Stage III Colon Cancer Patients Treated with Adjuvant FOLFOX Chemotherapy

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-11-1048 ◽

2011 ◽

Vol 17 (23) ◽

pp. 7470-7478 ◽

Cited By ~ 61

Author(s):

Aziz Zaanan ◽

Jean-François Fléjou ◽

Jean-François Emile ◽

Guetz Gaëtan Des ◽

Peggy Cuilliere-Dartigues ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Prognostic Biomarker ◽

Disease Free Survival ◽

Free Survival ◽

Stage Iii Colon Cancer ◽

Mismatch Repair Status ◽

Folfox Chemotherapy ◽

Disease Free ◽

Defective Mismatch Repair

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Efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for stage III colon cancer patients who underwent curative resection (KSCC1303).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.739 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 739-739

Author(s):

Nobutomo Miyanari ◽

Yasunori Emi ◽

Akihito Tsuji ◽

Kenji Sakai ◽

Hideaki Anai ◽

...

Keyword(s):

Colon Cancer ◽

Survival Rate ◽

Cancer Patients ◽

Curative Resection ◽

Disease Free Survival ◽

Dose Intensity ◽

Stage Iii ◽

Free Survival ◽

Stage Iii Colon Cancer ◽

Disease Free

739 Background: Adjuvant chemotherapy is an accepted treatment method to improve the survival rate of Stage III colon cancer patients. Recently, regimens including oxaliplatin were proven superior to 5-FU only regimens. The purpose of this study was to examine the efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for Stage III colon cancer patients who underwent curative resection. Methods: Colon cancer patients who had undergone curative resection were enrolled in this study. They received oral S-1 40-60 mg twice daily on days 1 to 14 every 3 weeks plus intravenous oxaliplatin 130 mg/m2 on day 1 for 24 months. The primary endpoint was 3-year disease-free survival. The secondary endpoints were the rate of treatment completeness, adverse events, relative dose intensity, disease-free survival and overall survival. Results: Between 2014 February and 2014 December, eighty-nine patients were enrolled in this study. One patient had to be excluded due to ineligibility. The other eighty-eight patients were analyzed. The rate of protocol treatment completeness was 72.3%. Relative dose intensity of S-1 and oxaliplatin were 72 and 76.3, respectively. Hematological severe adverse events (Grade 3/4) were neutropenia (21.3%) and thrombocytopenia (15.7%). The most frequent symptom was diarrhea (Grade 3/4: 5.6%). Six-month disease-free survival rate was 94.3% (95% confidential interval: 86.9-97.6%). Six-month overall survival rate was 98.9% (95% C.I.: 92.2-99.8%). Conclusions: C-SOX for Stage III colon cancer patients who underwent curative resection was safe and feasible. The long-term outcome should be evaluated in future studies. Clinical trial information: 000012618.

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Adjuvant active specific immunotherapy for human colorectal cancer: 6.5-year median follow-up of a phase III prospectively randomized trial.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.3.390 ◽

1993 ◽

Vol 11 (3) ◽

pp. 390-399 ◽

Cited By ~ 187

Author(s):

H C Hoover ◽

J S Brandhorst ◽

L C Peters ◽

M G Surdyke ◽

Y Takeshita ◽

...

Keyword(s):

Rectal Cancer ◽

Colon Cancer ◽

Cancer Patients ◽

Specific Immunotherapy ◽

Disease Free Survival ◽

Free Survival ◽

Active Specific Immunotherapy ◽

To Receive ◽

Disease Free

PURPOSE Patients with colon or rectal cancer were entered onto a prospectively randomized, controlled clinical trial of active specific immunotherapy (ASI) with an autologous tumor cell-bacillus Calmette-Guérin (BCG) vaccine. We investigated whether ASI could improve disease-free status and survival. PATIENTS AND METHODS Ninety-eight patients with Dukes' stage B2-C3 colon or rectal cancer were randomized into groups treated by resection alone or resection plus ASI. Eighty patients met all eligibility criteria. All patients with rectal cancer were to receive 50 Gy of pelvic irradiation. Analysis of distribution of survival and disease-free survival was made on all eligible patients until December 31, 1990. RESULTS As a single study, no statistically significant differences were detected in survival or disease-free survival for all 80 eligible patients. However, since it was recognized at the outset that there were treatment differences, in that rectal cancer patients were to receive postimmunotherapy radiation, it was considered that a cohort analysis of the colon and rectal cancer patients might be informative. With a median follow-up of 93 months, there is a significant improvement in survival (two-sided P = .02; hazards ratio, 3.97) and disease-free survival (two-sided P = .039; hazards ratio, 2.67) in all eligible colon cancer patients who received ASI. With a median follow-up of 58 months, no benefits were seen in patients with rectal cancer who received ASI. CONCLUSION This study suggests that ASI may be beneficial to patients with colon cancer.

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