Optimizing Adjuvant Therapy and Survivorship Care of Stage III Colon Cancer

Loree, Jonathan M.; Cheung, Winson Y.

doi:10.2217/fon-2016-0109

Cited by 10 publications

(5 citation statements)

References 100 publications

(76 reference statements)

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“…As an adjuvant therapy, FOLFOX chemotherapy can improve the postoperative survival rate of patients with stage III/II colon cancer patients [4][5][6]. However, adjuvant chemotherapy leads to the incidence of bone marrow suppression, and some patients fail to complete the established chemotherapy regimen [10].…”

Section: Discussionmentioning

confidence: 99%

“…Cytotoxic chemotherapy and radio-chemotherapy are used to treat patients with stage III CRC [4]. Fluorouracil (5-Fu), oxaliplatin, and cisplatin are the most effective chemotherapeutic agents for clinical chemotherapy [5,6]. Nevertheless, due to chemotherapeutic drug resistance, the survival rate of patients with CRC remains very low [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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The Gut Microbiota Metabolite Urolithin B Prevents Colorectal Carcinogenesis by Remodeling Microbiota and PD-L1/HLA-B

Wang

Chen

et al. 2023

Oxidative Medicine and Cellular Longevity

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Colorectal cancer has risen to the third occurring cancer in the world. Fluorouracil (5-Fu), oxaliplatin, and cisplatin are the most effective chemotherapeutic agents for clinical chemotherapy. Nevertheless, due to chemotherapeutic drug resistance, the survival rate of patients with CRC remains very low. In this study, we used the inflammation-induced or mutation-family-inherited murine CRC models to study the anticancer and immunotherapy effects of urolithin B (UB), the final metabolite of polyphenols in the gastrointestinal tract. The label-free proteomics analysis and the gene ontology (GO) classifications were used to test and analyze the proteins affected by UB. And 16S rDNA sequencing and flow cytometry were utilized to uncover gut microbiome composition and immune defense improved by UB administration. The results indicated that urolithin B prevents colorectal carcinogenesis by remodeling gut microbial and tumor immune microenvironments, such as HLA-B, NK cells, regulatory T cells, and γδ TCR cells, and decreasing the PD-L1. The combination of urolithin B with first-line therapeutic drugs improved the colorectal intestinal hematochezia by shaping gut microbiota, providing a strategy for the treatment of immunotherapy treatment for CRC treatments. UB combined with anti-PD-1 antibody could inhibit the growth of colon cancer. Urolithin B may thus contribute to anticancer treatments and provide a high immune response microenvironment for CRC patients’ further immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Gut Microbiota Metabolite Urolithin B Prevents Colorectal Carcinogenesis by Remodeling Microbiota and PD-L1/HLA-B

Wang

Chen

et al. 2023

Oxidative Medicine and Cellular Longevity

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“…[11][12][13] Recently, the prognosis for metastatic or unresectable CRC has improved owing to the approval of 5-FU for advanced CRC. 14,15 Meanwhile, a small population of colorectal cancer stem cells (CSCs) was identified on the basis of the cell membrane markers CD133 +, CD44 +, ESA + cells. 16,17 CSCs are closely correlated with tumor recurrence, metastasis and chemoradioresistance.…”

Section: Introductionmentioning

confidence: 99%

<p>Superior Effect of the Combination of Carbon-Ion Beam Irradiation and 5-Fluorouracil on Colorectal Cancer Stem Cells in vitro and in vivo</p>

Koom

Sai

Suzuki

et al. 2020

OTT

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Background The aim of this study was to investigate whether carbon-ion beam irradiation in combination with 5-fluorouracil (5-FU) is superior to carbon-ion beam irradiation alone in targeting colorectal cancer stem-like cells (CSCs). Materials and Methods Human colorectal cancer (CRC) cells, HCT116 and HT29, were treated with carbon-ion beam irradiation alone or in combination with 5-FU. Cell viability assay, colony and spheroid formation assay, apoptotic assay, and quantitative real-time PCR analysis of apoptosis- and autophagy-related gene expression were performed. Results Carbon-ion beam irradiation dose-dependently decreased CRC cell viability and showed significantly enhanced cell killing effect when combined with 5-FU. Carbon-ion beam irradiation in combination with 5-FU significantly increased the percentage of apoptotic cells. The expression of some apoptotic and autophagy-related genes such as Bax , Bcl2 , Beclin1 and ATG7 was significantly induced by carbon-ion beam irradiation alone and was further enhanced when the beam was combined with 5-FU. The spheroid forming capacity of CD133+ cell subpopulations was significantly inhibited by carbon-ion beam in combination with 5-FU. Histopathologically, the combination of carbon-ion beam irradiation and 5-FU destroyed more xenograft tumor cells, and resulted in increased necrosis, cavitation, and fibrosis, compared to carbon-ion beam irradiation alone. Conclusion In conclusion, carbon-ion beam treatment combined with 5-FU has the potential to kill CRC cells including CSCs by inducing increased apoptosis and autophagy.

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“…Furthermore recent findings suggest that a shorter adjuvant chemotherapy (3 months instead of 6) could be considered for low-risk stage III disease (T1-3 N1 tumors) ( Shi et al, 2017 ; Grothey et al, 2018 ). The introduction of the new targeted agents in the adjuvant setting has not brought any significant benefit ( Dienstmann et al, 2015 ; Gustavsson et al, 2015 ; Loree and Cheung, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

A Clinical-Genetic Score to Identify Surgically Resected Colorectal Cancer Patients Benefiting From an Adjuvant Fluoropyrimidine-Based Therapy

et al. 2018

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There are clinical challenges related to adjuvant treatment in colorectal cancer (CRC) and novel molecular markers are needed for better risk stratification of patients. Our aim was to integrate our previously reported clinical-genetic prognostic score with new immunogenetic markers of 5-year disease-free survival (DFS) to evaluate the recurrence risk stratification before fluoropyrimidine (FL)-based adjuvant therapy. The study population included a total of 270 stage II-III CRC patients treated with adjuvant FL with (FL + OXA, n = 119) or without oxaliplatin (FL, n = 151). Patients were genotyped for a panel of 192 tagging polymorphisms in 34 immune-related genes. The IFNG-rs1861494 polymorphism was associated with worse DFS in the FL + OXA (HR = 2.14, 95%CI 1.13–4.08; P = 0.020, q-value = 0.249) and FL (HR = 1.97, 95%CI 1.00–3.86; P = 0.049) cohorts, according to a dominant model. The integration of IFNG-rs1861494 in our previous clinical genetic multiparametric score of DFS improved the patients’ risk stratification (Log-rank P = 0.0026 in the pooled population). These findings could improve the discrimination of patients who would benefit from adjuvant treatment. In addition, the results may help better elucidate the interplay between the immune system and chemotherapeutics and help determine the efficacy of anti-tumor strategies.

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Optimizing Adjuvant Therapy and Survivorship Care of Stage III Colon Cancer

Cited by 10 publications

References 100 publications

The Gut Microbiota Metabolite Urolithin B Prevents Colorectal Carcinogenesis by Remodeling Microbiota and PD-L1/HLA-B

The Gut Microbiota Metabolite Urolithin B Prevents Colorectal Carcinogenesis by Remodeling Microbiota and PD-L1/HLA-B

<p>Superior Effect of the Combination of Carbon-Ion Beam Irradiation and 5-Fluorouracil on Colorectal Cancer Stem Cells in vitro and in vivo</p>

A Clinical-Genetic Score to Identify Surgically Resected Colorectal Cancer Patients Benefiting From an Adjuvant Fluoropyrimidine-Based Therapy

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