60 research outputs found

    Circulating lymphocyte is an important determinant of the effectiveness of preoperative radiotherapy in advanced rectal cancer

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    <p>Abstract</p> <p>Background</p> <p>Although preoperative radiotherapy (RT) is widely used as the initial treatment for locally advanced rectal cancer (RC) in the neoadjuvant setting, factors determining clinical response have not been adequately defined. In order to find other factors possibly related with radiosensitivity, we evaluated the relationships between circulating blood cell counts and RT effects.</p> <p>Methods</p> <p>In 179 cases with advanced RC, we retrospectively examined hemoglobin (Hb) levels and counts of white blood cells (WBC), platelets and WBC subsets before and after RT and investigated their associations with the complete response (CR) rate together with other clinicopathological factors.</p> <p>Results</p> <p>The ratio of lymphocytes in WBC taken before RT was significantly greater in 15 CR cases as compared with those in non-CR cases. Patients with high lymphocyte percentages (25.7%) showed better outcome than the counterparts. Conversely, the ratio of neutrophiles was reduced in CR cases. The lymphocyte ratio showed an independent association with CR with multivariate analysis, and tended to be maintained at relatively high levels in CR cases.</p> <p>Conclusions</p> <p>In RC patients, peripheral blood lymphocytes have a significant impact on the CR rate in response to RT. Lymphocyte-mediated immune reactions are supposed to have positive roles on clinical response in radiotherapy for RC.</p

    LINE-1 hypomethylation status of circulating cell-free DNA in plasma as a biomarker for colorectal cancer.

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    Colorectal cancer (CRC) is a serious public health problem and non-invasive biomarkers improving diagnosis or therapy are strongly required. Circulating cell-free DNA (cfDNA) has been a promising target for this purpose. In this study, we evaluated the potential of long interspersed nuclear element-1 (LINE-1) hypomethylation as a blood biomarker for CRC. LINE-1 hypomethylation level in plasma cfDNA in 114 CRC patients was retrospectively examined by absolute quantitative analysis of methylated alleles real-time PCR, and was expressed using LINE-1 hypomethylation index (LHI) [unmethylated copy number/ (methylated copy number + unmethylated copy number)]. Greater LHI values indicated enhanced hypomethylation. In our clinicopathological analysis, CRC patients with large tumors (≥6.0 cm), advanced N stage (≥2), and distant metastasis (M1) had statistically significantly higher cfDNA LHI than other CRC patients, suggesting cfDNA LHI as a disease progression biomarker for CRC. Furthermore, early stage I/II (n = 57) as well as advanced stage III/IV (n =57) CRC patients had significantly higher cfDNA LHI than healthy donors (n=53) [stage I/II: median 0.369 (95% confidence interval, 0.360-0.380) vs. 0.332 (0.325-0.339), P \u3c 0.0001; stage III/IV: 0.372 (0.365-0.388) vs. 0.332 (0.325-0.339), P \u3c 0.0001]. The receiver operating characteristic analysis showed that cfDNA LHI had the detection capacity of CRC with area under the curve(AUC) of 0.79 and 0.83 in stage I/II and stage III/IV CRC patients, respectively. The present study demonstrated for the first time the potential of plasma cfDNA LHI as a novel biomarker for CRC, particularly for early stage detection

    Self-Expandable Metal Stent Placement as a Bridge to Laparoscopic or Open Surgery for Obstructive Colorectal Cancer: Short-Term Outcomes of Nineteen Consecutive Cases

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    Purpose Laparoscopic colorectal resection is a feasible and less invasive procedure with short-term advantages compared with open surgery; however, the evidence for its efficacy for treating obstructive colorectal cancer (CRC) is lacking. In this study, we aimed to determine short-term outcomes of SEMS placement for obstructive CRC followed by laparoscopic colorectal resection.Methods As of August 2013, 51 patients with obstructive CRC underwent stent insertion. Thirty-two patients received palliation therapy not intended for tumor resection. After decompression of the proximal intestine, nine and 10 patients underwent laparoscopic and open surgery, respectively. Clinicopathological, intraoperative, and postoperative data were retrospectively collected.Results There were no differences in resection rates and curabilities between the two groups. All surgeries were performed with a single-stage anastomosis, and no anastomotic leakage was observed. There was one patient with abdominal morbidity in the open group (Open) and none in the Lap group. There was no mortality in either group. Time to flatus (3.4 ± 1.8 days, Lap; 2.6 ± 1.1 days, Open) and time to oral intake (7.9 ± 2.5 days, Lap; 7.7±1.9 days, Open) were similar between the groups. Postoperative hospitalization times for the Lap group were shorter, but the difference was not statistically significant (15.2 ± 3.9 days, Lap; 21 ± 11.7 days, Open, p = 0.21).Conclusion Our findings indicate that laparoscopic surgery combined with preoperative stent placement is feasible as well as safe compared with open surgery for obstructive CRC

    Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer

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    Although neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer (RC), markers to predict the treatment response have not been fully established. In 73 patients with advanced RC who underwent CRT in a neoadjuvant setting, we retrospectively examined the associations between the clinical effects of CRT and blood cell counts before and after CRT. Clinical or pathological complete response (CR) was observed in 10 (14%) cases. The CR rate correlated significantly with the size and the circumferential extent of the tumor. Hemoglobin level, white blood cell (WBC) count and platelet count before CRT did not show a significant difference between CR and non-CR cases. Interestingly, however, lymphocyte ratio in WBC was significantly higher (p = 0.020), while neutrophil ratio tended to be lower (p = 0.099), in CR cases, which was shown to be an independent association by multivariate analysis. When all the blood data obtained in the entire treatment period were evaluated, circulating lymphocyte count was most markedly decreased in the CRT period and gradually recovered by the time of surgery, while the numbers of neutrophils and monocytes were comparatively stable. Moreover, the lymphocyte percentage in samples obtained from CR patients was maintained at a relatively higher level than that from non-CR patients. Since tumor shrinkage is known to be dependent not only on the characteristics of tumor cells but also on various host conditions, our data raise the possibility that a lymphocyte-mediated immune reaction may have a positive role in achieving complete eradication of tumor cells. Maintenance of circulating lymphocyte number may improve the response to CRT in rectal cancer

    Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells

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    <p>Abstract</p> <p>Background</p> <p>Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells.</p> <p>Methods</p> <p>HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed.</p> <p>Results</p> <p>5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pre-treatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21<sup>Cip1 </sup>and p27<sup>Kip1 </sup>and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer effect of 5-FU.</p> <p>Conclusion</p> <p>Our findings suggest that the combination therapy with CQ should be a novel therapeutic modality to improve efficacy of 5-FU-based chemotherapy, possibly by inhibiting autophagy-dependent resistance to chemotherapy.</p
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