Predicting the response of localised oesophageal cancer to neo-adjuvant chemoradiation

Gillham, Charles; Reynolds, John V.; Hollywood, Donal

doi:10.1186/1477-7819-5-97

Cited by 17 publications

(8 citation statements)

References 86 publications

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“…Transcriptional activation of P21/WAF1/CIP1, either p53‐dependent or independent, inhibits the accumulation of cyclin‐CDK complexes and, therefore, causes G1/S and G2/M arrest. The cell cycle arrest caused by P21/WAF1/CIP1 has also been shown to stimulate the cleavage of caspase 9 resulting in apoptosis within the cell (Gillham et al, ). We showed that fucoidan induced accumulation of P21/WAF1/CIP1 in APL cells.…”

Section: Discussionmentioning

confidence: 99%

Fucoidan Suppresses the Growth of Human Acute Promyelocytic Leukemia Cells In Vitro and In Vivo

Atashrazm

Lowenthal

Woods

et al. 2015

Journal Cellular Physiology

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Fucoidan, a natural component of seaweeds, is reported to have immunomodulatory and anti-tumor effects. The mechanisms underpinning these activities remain poorly understood. In this study, the cytotoxicity and anti-tumor activities of fucoidan were investigated in acute myeloid leukemia (AML) cells. The human AML cell lines NB4, KG1a, HL60, and K562 were treated with fucoidan and cell cycle, cell proliferation, and expression of apoptotic pathways molecules were analyzed. Fucoidan suppressed the proliferation and induced apoptosis through the intrinsic and extrinsic pathways in the acute promyelocytic leukemia (APL) cell lines NB4 and HL60, but not in KG1a and K562 cells. In NB4 cells, apoptosis was caspase-dependent as it was significantly attenuated by pre-treatment with a pan-caspase inhibitor. P21/WAF1/CIP1 was significantly up-regulated leading to cell cycle arrest. Fucoidan decreased the activation of ERK1/2 and down-regulated the activation of AKT through hypo-phosphorylation of Thr(308) residue but not Ser(473). In vivo, a xenograft model using the NB4 cells was employed. Mice were fed with fucoidan and tumor growth was measured following inoculation with NB4 cells. Subsequently, splenic natural killer (NK) cell cytotoxic activity was also examined. Oral doses of fucoidan significantly delayed tumor growth in the xenograft model and increased cytolytic activity of NK cells. Taken together, these data suggest that the selective inhibitory effect of fucoidan on APL cells and its protective effect against APL development in mice warrant further investigation of fucoidan as a useful agent in treatment of certain types of leukemia.

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Section: Discussionmentioning

confidence: 99%

Fucoidan Suppresses the Growth of Human Acute Promyelocytic Leukemia Cells In Vitro and In Vivo

Atashrazm

Lowenthal

Woods

et al. 2015

Journal Cellular Physiology

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“…In 2000, lehnert et al reported that gene chips could be used to survey radiation-associated genes (12). physicians explored different gene expression patterns between radiosensitive and radioresistant tumors in uterine cervical cancer (13), and to predict the clinical rt response in esophageal cancer (14) by microarray methods. However, the study of crc and radiation-associated gene expression is still limited.…”

Section: Introductionmentioning

confidence: 99%

CDC25A, VAV1, TP73, BRCA1 and ZAP70 gene overexpression correlates with radiation response in colorectal cancer

Tok

2011

Oncol Rep

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Abstract. radiotherapy is increasingly used in adjuvant approaches for colorectal cancer (crc) to reduce local recurrence and improve survival. However, the principal limitation is the large variability in response among different individuals due to tumor heterogeneity. In the present study, we compared gene expression profiles between radiosensitive and radioresistant colorectal cancer cell lines to identify radiation-related molecules that can be used to evaluate the effects of radiation. the crc cell line sW620 was irradiated with a high-energy photo beam. Following radiation treatment, rnA was extracted from non-irradiated and irradiated cells, respectively, and gene expression analysis was performed by oligonucleotide microarray and the DAVID bioinformatics method. to further confirm the results, an additional 4 crc cell lines, colo205, t84, Hct116, sW480 and sW403 were purchased from Atcc. the radiosensitivities of each were determined by the survival fraction at 2 gray (sF2) of the surviving cells using the Atplite assay, and the gene expression profiles after irradiation among the radiosensitive and radioresistant cell lines were analyzed by membrane arrays. the relationships between gene expression and patient clinicopathological features were also analyzed using membrane arrays and rt-pcr. the results from oligonucleotide microarray analysis show that 1601 genes were up-regulated (gene expression ratio of post-to preradiation treatment >2). By bioinformatic database analysis, 30 up-regulated genes were identified as involved in DNA damage response pathways, immune response pathways and the complement and coagulation cascades pathway. Fifteen genes showed differential gene expression profiles between radiosensitive (Hct116 and sW620) and radioresistant crc cell lines (sW403 and sW480). In 110 crc tissues, we detected five genes CDC25A, VAV1, TP73, BRCA1 and ZAP70 from 15 overexpressed genes that significantly related to prognostic factors (tumor size, advanced stage, invasive depth, lymph node metastasis and differentiation). these findings suggest that cDc25A, VAV1, tp73, BrcA1 and ZAp70 may be novel markers for predicting the effectiveness of radiotherapy in crc patients.

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“…Gene expression profiling and identification of molecular signature may hold promise for the future. 16,17 In our study, 63% of the patients (n = 23) showed evidence of gross residual tumor on resection specimen. Although 19 subjects in this group received R0 resection, the prognosis remained dismal.…”

Section: Discussionmentioning

confidence: 45%

“…In our study, we were unable to identify any significant pretherapy predictor of pCR in patients with cT2N0 disease. Gene expression profiling and identification of molecular signature may hold promise for the future 16,17 …”

Section: Discussionmentioning

confidence: 99%

Long-term outcomes following neoadjuvant chemoradiotherapy in patients with clinical T2N0 esophageal squamous cell carcinoma

Chen

Chao

Chang³

et al. 2011

Diseases of the Esophagus

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The optimal treatment for patients with local esophageal cancer (cT2N0 disease) has not yet been defined. We sought to determine whether neoadjuvant chemoradiotherapy (CRT) can improve prognosis compared with direct esophagectomy in this patient group. Between 1994 and 2005, patients with cT2N0 esophageal squamous cell carcinoma who underwent either neoadjuvant CRT or surgery as first-line treatment were retrospectively reviewed. We collected information on their demographic characteristics, staging modality, clinical and pathological stages, perioperative course, and survival. The study endpoints included tumor recurrence, disease-specific survival (DSS), and overall survival rate. Of the 71 eligible patients, 14 received an esophagectomy first, whereas the remaining 57 received neoadjuvant CRT first. Despite the high pathological complete response (pCR) rate of 37% after neoadjuvant CRT, routine neoadjuvant CRT did not translate into better survival compared to direct surgery (5-year DSS: 39% vs. 68%, P= 0.17). The dramatic survival difference between pCR and non-pCR patients (5-year DSS: 85% vs. 4%, P < 0.001) accounts for these unsatisfactory results. In our series, the administration of neoadjuvant CRT to patients with clinical stage T2N0 esophageal squamous cell carcinoma did not significantly improve outcomes compared with direct esophagectomy.

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Predicting the response of localised oesophageal cancer to neo-adjuvant chemoradiation

Abstract: Currently there are no clinically useful predictors of response based on standard pathological assessment and immunohistochemistry. Genomics, proteomics and molecular imaging may hold promise.

Cited by 17 publications

References 86 publications

Fucoidan Suppresses the Growth of Human Acute Promyelocytic Leukemia Cells In Vitro and In Vivo

Fucoidan Suppresses the Growth of Human Acute Promyelocytic Leukemia Cells In Vitro and In Vivo

CDC25A, VAV1, TP73, BRCA1 and ZAP70 gene overexpression correlates with radiation response in colorectal cancer

Long-term outcomes following neoadjuvant chemoradiotherapy in patients with clinical T2N0 esophageal squamous cell carcinoma

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