Quercetin reverses 5-fluorouracil resistance in colon cancer cells by modulating the NRF2/HO-1 pathway.

Quercetin (Que) has been proven to enhance the chemosensitivity of multiple cancers, including colon cancer (CC). However, whether the combination of Que and 5-fluorouracil (5-FU) has a synergistic effect on drug-resistant CC cells has not previously been reported. The effect of Que (5 and 10 µg/mL) on cell vitality and apoptosis of CC and CC drug-resistant cells was examined using a cell counting kit-8 (CCK-8) and flow cytometry. After cells were treated with 5-FU (10, 40 µg/mL), Que (10 µM, 40 µM), or 5-FU in combination with Que, cell proliferation, apoptosis, oxidative stress-related factors, reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway-related factors were examined by colony formation assay, flow cytometry, ELISA, ROS kit, immunofluorescence assay, and Western blot. The results showed that 5-FU reduced cell viability and induced apoptosis of CC as well as 5-FU-resistant CC cells. Que further restrained the proliferation, oxidative stress-related factors (SOD, CAT, GPx, and GR), ROS production, and induced apoptosis in CC cells and 5-FU-resistant CC cells induced by 5-FU. Moreover, the combination of Que and 5-FU attenuated the Nrf2/HO-1 pathway-related marker levels in CC cells and 5-FU-resistant CC cells. Therefore, our results suggest that Que reverses 5-FU resistance in CC cells via modulating the Nrf2/HO-1 pathway.

Clinical Outcomes and Safety of Different Treatment Modes for Local Recurrence of Rectal Cancer.

OBJECTIVE: Optimal approaches to patients with local recurrence of rectal cancer are unclear in China. This study aimed to evaluaty -30te the clinical outcomes and toxicity associated with different treatment regimens for patients with local recurrence of rectal cancer. METHODS: A retrospective chart review of patients with local recurrence of rectal cancer and previous radical surgical treatment between March 2010 and December 2017 with curative intent was performed. Disease-related endpoints included treatment progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 5.0, and complications were scored according to the Clavien-Dindo classification. RESULTS: A total of 71 patients met the inclusion criteria in this study. The recurrence sites were mainly local recurrence in the pelvic cavity and regional lymph node metastasis. Twenty patients received chemoradiotherapy combined with surgery, 10 underwent surgery alone, and others received chemoradiotherapy-alone (n = 27) and chemotherapy-alone (n = 14) treatment. A clear difference was found in PFS between surgery/chemoradiotherapy with surgery and chemoradiotherapy/chemotherapy groups (26.6 months vs 14.1 months, P = 0.033). The PFS of patients in the surgery combined with chemoradiotherapy, surgery alone, and chemotherapy/chemoradiotherapy groups was 65.2 months, 20.2 months, and 14.2 months, respectively (P = 0.042). The multivariate analysis of PFS demonstrated that surgery was an independent factor. The proportion of patients with distant metastases after chemoradiotherapy/chemotherapy was higher than that of patients undergoing surgery (36.6% vs 21.4%, P = 0.179). The OS of patients in the surgery combined with chemoradiotherapy, surgery alone, and chemotherapy/chemoradiotherapy groups was 89.4 months, 66.0 months, and 62.8 months, respectively (P = 0.189). Radiation treatment and surgery did not increase extra severe toxicities. CONCLUSION: Surgery combined with chemoradiotherapy was a beneficial treatment mode for managing patients with locally recurrent, nonmetastatic rectal cancer. It was associated with better local disease control, no increase in toxicity, and prolonged survival among patients with locally recurrent rectal cancer.

Correlation between Chemokine CXCL-12 and ist Receptor CXCR4 Expression is Associated with Clinical Prognosis of Gastric Cancer.

BACKGROUND: To analyze the differences in gene expression levels of chemokine CXCL-12 and its receptor CXCR4 in gastric cancer and the relationship between their correlations with the clinical prognosis of gastric cancer. METHODS: The information on gastric cancer in the TCGA (The Cancer Genome Atlas) database was downloaded from the Broad GDAC FIREHOSE, including CXCL-12 and CXCR4 gene expression data of 415 gastric cancer tissues and 35 normal gastric tissues; clinical information of 392 gastric cancer cases. All patients were divided into either a correlated (significantly higher or lower correlation between CXCL12 and CXCR4 expression) or uncorrelated groups. Wilcoxon rank sum test was used to analyze the differential gene expressions of CXCL-12 and CXCR4 between gastric cancer tissues and normal gastric tissues. Furthermore, one-way analysis of variance and Kaplan-Meier survival analysis were used to analyze the differential gene expressions of CXCL-12 and CXCR4 and the prognosis in patients with different stages of gastric cancer. Gastric cancer patients were divided into two groups according to whether CXCL-12 and CXCR4 gene expressions were correlated or not. Kaplan-Meier survival analysis was used to analyze the three-year survival of the two groups. RESULTS: There were differences between CXCL-12 and CXCR4 expression in 415 gastric cancer tissues and 35 normal gastric tissues. No statistically significant difference between CXCL-12 and CXCR4 was detected in different stages of gastric cancer. There were differences of the five-year survival in different stages of gastric cancer. Further analysis showed that the three-year survival in the correlated group was superior compared to the uncor-related one. CONCLUSIONS: The gene expression of CXCL-12 and CXCR4 was significantly different between gastric cancer tissues and normal gastric tissues. Moreover, the correlation between CXCL-12 and CXCR4 gene expression may be used as a predictor of clinical prognosis in patients with gastric cancer.

Preoperative chemoradiotherapy with 5-fluorouracil and oxaliplatin for locally advanced rectal cancer: long-term results of a phase II trial.

The aim of this study was to report long-term results of patients with locally advanced rectal cancer treated by neoadjuvant chemoradiotherapy with fluorouracil, leucovorin, and oxaliplatin. From February 2002 to November 2006, a total of 58 patients with locally advanced rectal cancer were recruited. Secondary endpoints included the cumulative incidence of local and distant recurrences, disease-free survival, and overall survival. The median follow-up time was 138 months (109-151 months). The cumulative incidence of local recurrence at 10 years was 12.1%. The cumulative incidence of distant recurrence at 10 years was 53.4%. The overall survival in the intention-to-treat population was 39.5% at 10 years. Disease-free survival in the intention-to-treat population was 41.8% at 10 years. Univariate analysis revealed that pathologic complete response was associated with local recurrence, distant recurrence, disease-free survival, and overall survival (p < .05). Distant recurrence remains the predominant pattern of failure for patients with locally advanced rectal cancer after preoperative chemoradiotherapy and total mesorectal excision. Pathologic complete response is an independent prognostic factor for locally advanced rectal cancer after preoperative chemoradiotherapy.

Upregulation of circulating cytokeratin 20, urokinase plasminogen activator and C-reactive protein is associated with poor prognosis in gastric cancer.

Gastric cancer is one of the most common types of cancer, with a high mortality rate. The aim of this study was to investigate the role of several key molecules, including cytokeratin (CK) 19 and CK20, urokinase plasminogen activator (uPA), C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9, which are involved in cancer invasion and metastasis, in order to determine whether they may be considered as novel prognostic factors for gastric cancer. Peripheral blood was collected from 165 patients with gastric adenocarcinoma who underwent curative surgical resection at Zhejiang Cancer Hospital (Hangzhou, China) between 2010 and 2011. The mRNA levels of CK19, CK20, uPA and MMP-9 were detected by reverse transcription-quantitative polymerase chain reaction. The protein expression of CRP was measured by immunoturbidimetry. The Students t-test was used in the univariate analyses and the Kaplan-Meier method was used to analyze the survival curves. The relative mRNA expression of CK19 and MMP-9 was not found to be significantly associated with gender, age or cancer stage, whereas that of CK20 and uPA was associated with gastric cancer stage: The low-expression group was associated with early-stage and the high-expression group with more advanced-stage disease (P<0.05). The CRP protein level was associated with gender and cancer stage: The low-expression group was predominantly associated with male gender and early-stage disease, whereas the high-expression group was associated with female gender and advanced-stage disease (P<0.05). The expression of CK19, CK20, uPA and CRP, but not MMP-9, was negatively associated with overall survival (OS): The OS rate in the high-expression groups was significantly lower compared with that in the low-expression groups (P<0.05). In conclusion, the upregulation of CK20, uPA and CRP was found to be a negative prognostic factor for gastric cancer.

Prognostic value of phospho-Akt in patients with non-small cell lung carcinoma: a meta-analysis.

Previous studies have been inconsistent with respect to the reported associations between phospho-Akt (p-Akt) overexpression and lung cancer prognosis. In this study, we conducted a systematic review and meta-analysis to assess the prognostic value of p-Akt in patients with non-small cell lung carcinoma (NSCLC). Relevant articles were identified by searching MEDLINE. Hazard risks (HRs) from individual studies were calculated and pooled by using a random-effect model, and heterogeneity and publication bias analyses were also performed. Finally, 18 studies comprising 2,353 patients were included in the meta-analysis. p-Akt overexpression was associated with worse survival in NSCLC patients, and the pooled HRs for all the studies was 1.38 (95% confidence interval [CI]: 1.11-1.70; p<0.01). After subgroup analysis, the association was strengthened in the surgery treatment group, with an HR of 1.44 (95% CI: 1.19-1.75; p<0.01), while in the tyrosine kinase inhibitors treatment group, the statistical significance disappeared (HR: 1.22, 95% CI: 0.70-2.14; p=0.48). The HR in cases of early stage disease (I-III) was 1.35 (95% CI: 1.08-1.69; p=0.04); however, in cases of late stage disease (III-IV), the association became non-significant (HR: 1.22, 95% CI: 0.64-2.33; p=0.54). Our results suggest that there was a significantly inverse association between p-Akt overexpression and the prognosis of NSCLC patients, and that this association appeared to be limited in early-stage patients who underwent surgery.

Clinical research on nourishing yin and unblocking meridians recipe combined with opioid analgesics in cancer pain management.

OBJECTIVE: To investigate the analgesic effects of Nourishing yin and Unblocking meridians Receipe (NUR) combined with opioid analgesics in managing cancer pain. METHODS: All the patients enrolled were differentiated as of yin deficiency and meridian blocked syndrome type of TCM. Forty-one of them in the treated group were treated with NUR combined with opioid analgesics, while 43 of them in the control group were given opioid analgesics alone with successive 14 days as one treatment course for both groups. RESULTS: The indexes of the treated group were superior to those in the control group as to the degree of pain-relieving, the therapeutic effect of analgesia, the occurrence frequency of cancer pain every day and its duration each time, the analgesic initial time, and the quality of life. CONCLUSION: NUR combined with opioid analgesics in cancer pain management was more effective than opioid analgesics alone.