To compare the acute gastrointestinal (GI) and genitourinary (GU) toxicity profiles between intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in rectal cancer patients treated with neoadjuvant chemoradiation (NCRT) using meta-analysis and pooled-analysis from published articles. Literature search was performed in PubMed and EMBASE from inception to March 2017. The odd ratios (ORs) were calculated and random effects model was used for meta-analysis. Chi-square or Fisher’s exact test was performed for the pooled-analysis. Six studies including a total of 859 patients met the inclusion criteria. Most patients (98.7%) received NCRT. In the meta-analysis, IMRT reduced grade ≥ 2 acute overall GI toxicity, diarrhea and proctitis with ORs of 0.38, 0.32 and 0.60, respectively (all P < 0.05), compared to 3DCRT. IMRT also reduced acute grade ≥ 3 proctitis compared to 3D-CRT (OR, 0.24; P = 0.03). No significant heterogeneity or publication bias was detected. In the pooled-analysis, IMRT reduced the incidence of grade ≥ 2 acute overall GI toxicity, diarrhea, proctitis and GU toxicity (all P < 0.05). Moreover, lower incidence of grade ≥ 3 acute overall GI toxicity, diarrhea and proctitis were observed in the patients treated with IMRT (all P < 0.05). IMRT significantly reduced acute toxicity in locally advanced rectal cancer patients treated with NCRT compared to 3DCRT.

The epidermal growth factor receptor (EGFR)/RAS/RAF/MEK/MAPK pathway is an important pathway in the carcinogenesis, invasion and metastasis of colorectal cancers (CRCs). We conducted a retrospective study to determine the prognostic values of EGFR expression and KRAS mutation in patients with metastatic CRC (mCRC) based on synchronous or metachronous status. From October 2002 to March 2012, 205 patients with mCRC were retrospectively analyzed; 98 were found to have metachronous mCRC while 107 were found to have synchronous mCRC. The EGFR expressions were determinate by IHC (immunohistochemistry) analysis and categorized 1+ (weak intensity), 2+ (moderate intensity), and 3+ (strong intensity). Genomic DNA was isolated from frozen primary CRC tissues and direct sequencing of KRAS was performed. The clinicopathological features of these mCRC patients were retrospectively investigated according to EGFR expression and KRAS mutation status. Moreover, we analyzed the prognostic values of EGFR expression and KRAS mutation among these patients. Of the 205 patients with mCRC, EGFR expression was analyzed in 167 patients, and positive EGFR expression was noted in 140 of those patients (83.8%). KRAS mutation was investigated in 205 patients and mutations were noted in 88 of those patients (42.9%). In patients with metachronous mCRC, positive EGFR expression was significantly correlated with well-and moderately-differentiated tumors (P = 0.028), poorer disease-free survival (DFS) (P < 0.001), and overall survival (OS) (P < 0.001). Furthermore, positive EGFR expression was a significant independent prognostic factor of DFS (P = 0.006, HR: 4.012, 95% CI: 1.130–8.445) and OS (P = 0.028, HR: 3.090, 95% CI: 1.477–10.900) in metachronous mCRC patients. KRAS mutation status was not significantly related to DFS and OS of patients with metachronous mCRC; likewise, KRAS mutation status was not significantly different in the progression-free survival (PFS) and OS of patients with synchronous mCRC (all P > 0.05). The present study demonstrated that EGFR expression has prognostic value only for patients with metachronous mCRC. However, KRAS mutation did not have prognostic value in patients with metachronous or synchronous mCRC.

After a low anterior resection, creating a defunctioning stoma is vital for securing the anastomosis in low-lying rectal cancer patients receiving concurrent chemoradiotherapy. Although it decreases the complication and reoperation rates associated with anastomotic leakage, the complications that arise before and after stoma closure should be carefully evaluated and managed. This study enrolled 95 rectal cancer patients who received neoadjuvant concurrent chemoradiotherapy and low anterior resection with anastomosis of the bowel between July 2010 and November 2012. A defunctioning stoma was created in 63 patients during low anterior resection and in another three patients after anastomotic leakage. The total complication rate from stoma creation to closure was 36.4%. Ileostomy led to greater renal insufficiency than colostomy did and significantly increased the readmission rate (all p < 0.05). The complication rate related to stoma closure was 36.0%. Patients with ileostomy had an increased risk of developing complications (p = 0.017), and early closure of the defunctioning stoma yielded a higher incidence of morbidity (p = 0.006). Multivariate analysis revealed that a time to closure of ≤109 days was an independent risk factor for developing complications (p = 0.007). The optimal timing of stoma reversal is at least 109 days after stoma construction in rectal cancer patients receiving concurrent chemoradiotherapy and low anterior resection.

Patients with locally advanced colon cancer (LACC) have a relatively poor prognosis despite radical resection and adjuvant chemotherapy. This study investigated the treatment efficacy and toxicity of neoadjuvant chemoradiotherapy in patients with LACC. We retrospectively reviewed 36 patients with LACC preoperatively treated with chemotherapy and radiotherapy. Patients were administered chemoradiotherapy, which comprised radiotherapy and neoadjuvant chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks. Median age was 64 years (45–86 years) and median follow-up period was 23.5 months (5.0–49.1 months). Seven (19.4%) patients developed grade 3 or 4 adverse events during neoadjuvant concurrent chemoradiotherapy. Pathologic responses were not evaluated in two patients who did not undergo radical resection. Of the 34 patients who underwent surgery, nine (26.4%) achieved a pathologic complete response (pCR). The 2-year estimated overall survival and disease-free survival rates were 88.7% and 73.6%, respectively. Our results demonstrated that neoadjuvant chemoradiotherapy is feasible and safe. A prominent pCR rate with an acceptable toxicity profile suggests that the multimodality therapy might be a treatment option for patients with LACC.

Cancer stem cells (CSCs) are a subset of cancer cells in tumors or established cancer cell lines that can initiate and sustain the growth of tumors in vivo. Cancer stem cells can be enriched in serum-free, suspended cultures that allow the formation of tumorspheres over several days to weeks. Brefeldin A (BFA) is a mycotoxin that induces endoplasmic reticulum (ER) stress in eukaryotic cells. We found that BFA, at sub-microgram per milliliter concentrations, preferentially induced cell death in MDA-MB-231 suspension cultures (EC₅₀: 0.016 µg/mL) compared to adhesion cultures. BFA also effectively inhibited clonogenic activity and the migration and matrix metalloproteinases-9 (MMP-9) activity of MDA-MB-231 cells. Western blotting analysis indicated that the effects of BFA may be mediated by the down-regulation of breast CSC marker CD44 and anti-apoptotic proteins Bcl-2 and Mcl-1, as well as the reversal of epithelial-mesenchymal transition. Furthermore, BFA also displayed selective cytotoxicity toward suspended MDA-MB-468 cells, and suppressed tumorsphere formation in T47D and MDA-MB-453 cells, suggesting that BFA may be effective against breast cancer cells of various phenotypes.

We evaluated the clinicopathologic features and outcomes of Taiwanese patients with right-sided versus left-sided colon cancer according to various cancer stages. A total of 1095 patients with primary colorectal cancer (CRC) undergoing surgery at a single-institution were enrolled. We analyzed patient differences in terms of clinicopathologic features, overall survival (OS) and cancer-specific survival (CSS) of right- versus left-sided colon cancer. Right-sided colon cancers were noted in 249 (22.7 %) patients, and left-sided colon cancers were noted in 846 (77.3 %) patients. Right-sided colon cancers were found to be significantly larger (P = 0.003) and poorly differentiated (P < 0.001), while also exhibiting advanced depth of tumor invasion (P = 0.002) and advanced UICC/AJCC stage (P = 0.016). Patients with right-sided colon cancers had both poorer OS and CSS than those with left-sided colon cancers (P = 0.021 and 0.023, respectively). However, analysis by various stages revealed significant OS and CSS differences (P = 0.002 and 0.002, respectively) between right-sided and left-sided colon cancers only in stage III patients. This study demonstrated poorer OS and CSS in patients with right-sided versus those with left-sided colon cancers, but significant differences were noted only in stage III patients.