[Corrigendum] Induction of microRNA­let­7a inhibits lung adeno-carcinoma cell growth by regulating cyclin D1.

After the publication of the article, an interested reader drew to the authors' attention that, in the western blots shown in Fig. 5C and D, a pair of data panels were inadvertently duplicated comparing between panels (C) and (D); in addition, the cell migration data shown in Fig. 7F on p. 1852 were selected incorrectly. The authors have examined their original data, and realize that these errors arose inadvertently as a consequence of their mishandling of their data. The revised versions of Figs. 5 and 7, featuring the corrected data for the caspase-8 experiment in Fig. 5C and alternative data for the cell migration assay experiments in Fig. 7F, are shown on the next two pages. The revised data shown for these Figures do not affect the overall conclusions reported in the paper. All the authors agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. Furthermore, the authors apologize to the readership for any inconvenience caused. [Oncology Reports 40: 1843-1854, 2018; DOI: 10.3892/or.2018.6593].

Postoperative Chemoradiotherapy With Capecitabine and Oxaliplatin vs Capecitabine for Stage II to III Rectal Cancer: A Randomized Clinical Trial.

Importance: Several studies have explored the efficacy and toxic effects of concurrent 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) with or without oxaliplatin in the neoadjuvant setting. Addition of oxaliplatin to 5-FU or capecitabine elicited similar outcomes but with significantly increased toxic effects; however, there is a need for randomized clinical trials comparing 2 CRT regimens for patients receiving CRT in the adjuvant setting. Objective: To explore the efficacy and toxic effects of oxaliplatin combined with postoperative concurrent capecitabine and radiotherapy (RT) for pathological stage II and III rectal cancer. Design, Setting, and Participants: This multicenter randomized clinical trial enrolled patients from 7 centers in China between April 1, 2008, and December 30, 2015. Patients with pathologically confirmed stage II and III rectal cancer were randomized (1:1) to receive concurrent CRT with capecitabine or capecitabine plus oxaliplatin. Analysis was conducted from December 31, 2019, to March 15, 2020. Interventions: RT comprised 45 to 50 Gy in 25 fractions of 1.8 to 2.0 Gy over 5 weeks. In the capecitabine with RT group, concurrent chemotherapy included 2 cycles of capecitabine (1600 mg/m2) on days 1 to 14 and 22 to 35. The capecitabine and oxaliplatin with RT group received identical postoperative RT to that in the capecitabine with RT group combined with capecitabine (1300 mg/m2) on days 1 to 14 and 22 to 35 and a 2-hour infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Patients in both groups received adjuvant chemotherapy (capecitabine or fluorouracil and oxaliplatin) after CRT. Main Outcomes and Measures: The primary end point was 3-year disease-free survival (DFS). Results: A total of 589 patients (median [IQR] age, 55 [47-52] years; 375 [63.7%] men and 214 [36.3%] women) were enrolled, including 294 patients randomized to the capecitabine with RT group and 295 patients randomized to the capecitabine and oxaliplatin with RT group. Median (IQR) follow-up was 68 (45-96) months. Most patients had stage III disease (574 patients [75.9%]). Three-year DFS was 76.3% for the capecitabine with RT group and 74.1% for the capecitabine and oxaliplatin with RT group, and 5-year DFS was 72.0% for the capecitabine with RT group and 71.1% for the capecitabine and oxaliplatin with RT group (hazard ratio [HR], 1.07; 95% CI, 0.79-1.44; P = .68). There was no significant difference between groups in overall survival (HR, 0.93; 95% CI, 0.64-1.34; P = .70) or local recurrence (HR, 0.61; 95% CI, 0.31-1.22; P = .16). More grade 3 and 4 acute toxic effects were observed in the capecitabine and oxaliplatin with RT group than in the capecitabine with RT group (114 patients [38.6%] vs 84 patients [28.6%]; P = .01). Conclusions and Relevance: This randomized clinical trial found that addition of oxaliplatin to capecitabine-based postoperative CRT did not improve the efficacy of treatment but increased the risk of severe acute toxic effects. This finding highlights the basic role of postoperative capecitabine with RT for patients with locally advanced rectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT00714077.

Induction of microRNA­let­7a inhibits lung adenocarcinoma cell growth by regulating cyclin D1.

Lung cancer is the most common cause of cancer­associated mortality. MicroRNAs (miRNAs), as oncogenes or tumor suppressor genes, serve crucial roles not only in tumorigenesis, but also in tumor invasion and metastasis. Although miRNA­let­7a (let­7a) has been reported to suppress cell growth in multiple cancer types, the biological mechanisms of let­7a in lung adenocarcinoma are yet to be fully elucidated. In the present study, the molecular roles of let­7a in lung adenocarcinoma were investigated by detecting its expression in lung adenocarcinoma tissues and exploring its roles in the regulation of lung cancer cell proliferation. Let­7a expression was identified to be downregulated in lung adenocarcinoma tissues compared with normal tissues. Overexpression of let­7a effectively suppressed cancer cell proliferation, migration and invasion in H1299 and A549 cells. Let­7a also induced cell apoptosis and cell cycle arrest. Furthermore, let­7a significantly inhibited cell growth by directly regulating cyclin D1 signals. This novel regulatory mechanism of let­7a in lung adenocarcinoma provides possible avenues for future targeted therapies of lung cancer.

Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial.

The aim of this study is to present an interim analysis of a phase III trial (NCT00714077) of postoperative concurrent capecitabine and radiotherapy with or without oxaliplatin for pathological stage II and III rectal cancer. Patients with pathologically confirmed stage II and III rectal cancer were randomized to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). The primary endpoint was 3-year disease-free survival rate (DFS). The 3-year DFS rate was 73.9% in the Capox-RT group and 71.6% in the Cap-RT group (HR 0.92, p = 0.647), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence and distant metastasis between the two groups (p > 0.05). More grade 3-4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group (38.1% vs. 29.2%, p = 0.041). Inclusion of oxaliplatin in the capecitabine-based postoperative regimen did not improve DFS but increased toxicities for pathological stage II and III rectal cancer in this interim analysis.

Zinc finger protein X-linked is overexpressed in colorectal cancer and is associated with poor prognosis.

Zinc finger protein X-linked (ZFX) is a zinc finger transcription factor and plays a significant role in the self-renewal ability of embryonic stem cells and various cancers. However, its expression and function in colorectal cancer (CRC) remain unclear. In the present study, we evaluated the expression of ZFX in CRC using quantitative polymerase chain reaction (qPCR), western blot analysis and immunohistochemistry (IHC), and further explored its potential functions in CRC cell lines using cell counting kit-8 and Transwell invasion assays. qPCR and western blot analysis revealed that ZFX was significantly upregulated in CRC tissues; IHC further confirmed this finding, revealing that higher expression of ZFX was significantly associated with larger tumor size (P=0.01), higher pathological stage (P=0.02), depth of invasion (P=0.047), lymph node invasion (P=0.02) and higher American Joint Committee on Cancer (AJCC) stage (P=0.04). CRC patients with higher ZFX expression also exhibited significantly shorter survival times (P=0.019). Moreover, knockdown of ZFX significantly suppressed proliferation and invasion in CRC cell lines HCT116 and LoVo. These results suggest that ZFX plays a notable role in CRC tumorigenicity and may serve as a novel marker and therapeutic target for CRC.

Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer.

PURPOSE: The aim of the study was to evaluate the safety and efficacy of adding concurrent nimotuzumab to preoperative radiotherapy with concurrent capecitabine in locally advanced rectal cancer. METHODS AND MATERIALS: Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive weekly nimotuzumab (400 mg; days -6, 1, 8, 15, 22, and 29). Capecitabine (825 mg/m(2)) was delivered orally twice daily for the duration of radiotherapy. Radiotherapy was administered at 50.4 Gy (45 + 5.4 Gy). The main endpoint was the pathologic complete response (pCR) rate. RESULTS: Twenty-one patients with T3 or T4 disease were enrolled; 66.7 % were nodal-positive; the median distance from the anal verge was 5.5 cm. A pCR was achieved in four patients (19.0 %); 71.4 % patients obtained moderate or good tumor regression (Grade 2 and 3). Downstaging occurred in 15/21 (71.4 %) patients by T stage and 11/14 (78.6 %) by N stage. The actual dose intensities (median/mean, %) were nimotuzumab (100, 100) and capecitabine (100, 99.5). The most frequent Grade 1/2 toxicities were radiation dermatitis (57.1 %), nausea/vomiting (52.4 %), leukocytopenia (47.6 %), diarrhea (47.6 %), and proctitis (38.1 %). Grade 3 diarrhea was observed in 9.5 % of patients and Grade 3 leukocytopenia in 4.8 %. CONCLUSION: These preliminary results indicate that nimotuzumab can be safely combined with radiotherapy plus concurrent capecitabine. The efficacy of this regimen (pCR = 19.0 %) was significantly higher than that observed in previous phase II trials of preoperative radiotherapy with concurrent capecitabine and cetuximab in rectal cancer. Further investigation of concurrent nimotuzumab with radiotherapy plus capecitabine is warranted.

Efficacy and safety of bevacizumab in Chinese patients with metastatic colorectal cancer.

OBJECTIVE: To evaluate the efficacy and safety of bevacizumab in the treatment of patients with metastatic colorectal cancer (mCRC). METHODS: In a single-center, observational study of 91 Chinese patients with mCRC who received bevacizumab in combination with chemotherapy was conducted. OBJECTIVE response rates (ORRs), progression-free survival (PFS), overall survival (OS) and adverse events were recorded, and the relationships between various clinical factors and PFS or OS were evaluated by Cox proportional hazards models. RESULTS: Treatment with bevacizumab and chemotherapy was effective and tolerable. Univariate analysis showed that PFS and OS were significantly associated with the Eastern Cooperative Oncology Group performance status (ECOG- PS) score, duration of bevacizumab exposure, and whether chemotherapy was continued after discontinuation of bevacizumab treatment. A multivariate analysis showed that the duration of bevacizumab exposure and whether chemotherapy was continued after discontinuation of bevacizumab were independent prognostic factors for PFS and OS. CONCLUSION: In Chinese mCRC population, the shorter the duration of exposure to bevacizumab and chemotherapy, the worse the prognosis is.

Treatment of high-risk gastric cancer postoperatively using intensity-modulated radiotherapy: a single-institution experience.

BACKGROUND/AIMS: The aim of this study was to determine the efficacy and acute toxicity of our early experience with treating postoperatively non-metastatic gastric cancer with intensity-modulated radiotherapy (IMRT). METHODOLOGY: A retrospective review was performed on 47 consecutive patients with gastric cancer and treated with postoperatively adjuvant IMRT at Department of radiation oncology, Zhejiang cancer hospital, China, between January 2007 and August 2009. One patient who did not complete his radiation course was excluded, leaving 46 patients for analyses. The median radiation dose delivered was 4500cGy using 180cGy fractions. Concurrent chemotherapy administered were 5-fluorouracil (n=36), capecitabine (n=9) and none (n=1). RESULTS: The median follow-up time was fifteen months (range 6-28 months). 1-year OS and 2-year OS were 98.0% and 80.0%, assessed by Kaplan-Meier methods. Of the six patients who died, five (83.3%) developed a distant metastases. The overall survival time by tumor size was significantly different (>6cm vs. =6cm, p<0.05). There was no significant survival difference between 5-fluorouracil group and capecitabine group (p=0.80). CONCLUSIONS: The data support the use of IMRT in the adjuvant treatment in high risk gastric cancer postoperatively. Acute toxicity is tolerable. Capecitabine with concurrent IMRT was as effective and tolerable as 5-FU/IMRT. Distant metastasis was the main reason of treatment failure that must be addressed in future trials.

Inflammatory cytokine gene polymorphisms increase the risk of atrophic gastritis and intestinal metaplasia.

AIM: To investigate the effects of interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF) gene polymorphisms, Helicobacter pylori (H. pylori) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM). METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progression group (no histological progression from normal or superficial gastritis, n = 137), group I (progressed from normal or superficial gastritis to SCAG, n = 134) and group II (progressed from normal or superficial gastritis to IM, n = 101). IL-8, MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing. RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection. CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.

Trihalomethane, haloacetonitrile, and chloral hydrate formation potentials of organic carbon fractions from sub-tropical forest soils.

Forest landscapes represent the major land-cover type for the watersheds of the East River, which is the source of water for 40 million people in South China. Forest soils with high levels of organic carbon are a potential terrestrial source of dissolved organic carbon (DOC) into the East River. DOC is of great concern, since it can form carcinogenic disinfection byproducts (DBPs) during drinking water treatment. In this study, soils from three altitudes (200, 450 and 900 m) in the Xiangtou Mountain Nature Reserve in South China, representing soils from evergreen moon forest, transitional evergreen broadleaf forest, and evergreen broadleaf forest, respectively, were evaluated for their potential contributions of DBP precursors into the East River. The water extractable organic carbon (WEOC) in three forest soils was physically and chemically fractionated into particulate organic carbon (1.2-0.45 microm), colloidal organic carbon (0.45-0.22 microm), and dissolved organic carbon (DOC) (<0.22 microm), hydrophobic acid (HPOA), transphilic acid and hydrophilic acid and were analysed for the formation potentials of trihalomethanes (THMs), haloacetonitriles (HANs), and chloral hydrate (CHD). Also, soils were incubated at 15, 25 and 35 degrees C for 14d in darkness to examine the impact of temperature effects on the availability and characteristics of WEOC. The extraction study showed that the amount of WEOC was proportional to soil organic carbon content, of which about 1% was water extractable. Regardless of soil type, DOC and HPOA were the most reactive fractions in forming THMs, CHD, and HANs. Production of DOC and HPOA in WEOC increased over 14 d incubation as incubation temperature increased, but the temperature did not alter the distribution of physical and chemical fractions and their reactivity in DBP formation. Results suggest higher inputs of DOC and DBP precursors from forest watersheds into source water may result in a warmer environment.

[Expression and significance of Elf-1 and vascular endothelial growth factor in non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: The roles of vascular endothelial growth factor (VEGF) in tumor angiogenesis is related with Ets family. Elf-1, a member of Ets family, has seldom been studied. This study aimed to investigate the expression of Elf-1 and VEGF in non-small cell lung cancer (NSCLC), and explore their correlations to clinicopathologic features of NSCLC. METHODS: Tissue microarray containing 69 specimens of NSCLC and six specimens of normal lung tissues was constructed. The expression of Elf-1 and VEGF was detected by PowerVision-9000 immunohistochemistry. RESULTS: Elf-1 and VEGF were not detected in all normal tissues; the positive rates of Elf-1 and VEGF were 72.46% and 63.77% in NSCLC, respectively. The expression levels of both Elf-1 and VEGF were significantly related with tumor differentiation, lymphatic metastasis, clinical stage, and postoperative survival time (all P < 0.01). Overexpression of them was related with poor prognosis: the survival rates were significantly lower in positive patients than in negative patients (both P < 0.01). Elf-1 expression was positively correlated to VEGF expression (r = 0.702, P < 0.01). CONCLUSIONS: The expression of Elf-1 and VEGF in NSCLC is related to differentiation, lymphatic metastasis, clinical stage and prognosis. Detecting their expression in combination can help to predict the malignant behavior of NSCLC.

[Efficacy assessment of preoperative radiochemotherapy and analysis of associated factors in rectal cancer].

OBJECTIVE: To evaluate the efficacy of preoperative radiochemotherapy and investigate the influencing factors in rectal cancer. METHODS: Fifty-three patients with locally advanced rectal cancer were treated with radiochemotherapy before surgery. Three-field technique of radiation therapy was administered with 46 Gy, 2 Gy per fraction, five times a week. Two cycles of chemotherapy were carried out at day 1, 2 and day 21, 22 during the radiation course. Surgery was performed 4-6 weeks after the radiochemotherapy. Response of preoperative radiochemotherapy was evaluated in all the patients by endoscopic ultrasonography (EUS), spiral computed tomography (SCT) and pathology. Influencing factors of the efficacy of radiochemotherapy were evaluated by univariate and Logistic analysis. RESULTS: Univariate analysis revealed that tumor size and histological grading were associated with the efficacy of preoperative radiochemotherapy. Logistic regression analysis showed that only tumor size was the significant predictive factor for response to preoperative radiochemotherapy. All patients underwent surgical resection after preoperative radiochemotherapy. The tumor was reduced by an average of 32.1%. T-level down-staging was 64.2%. Nodal negativity was 58.1%. Complete pathologic remission occurred in 11 patients. CONCLUSIONS: Preoperative radiochemotherapy can shrink the primary tumor and decrease lymph node metastasis rate. Patient with small tumor may have better response to preoperative radiochemotherapy.

Expression of connective tissue growth factor in tumor tissues is an independent predictor of poor prognosis in patients with gastric cancer.

AIM: To examine the expression of connective tissue growth factor (CTGF), also known as CCN2, in gastric carcinoma (GC), and the correlation between the expression of CTGF, clinicopathologic features and clinical outcomes of patients with GC. METHODS: One hundred and twenty-two GC patients were included in the present study. All patients were followed up for at least 5 years. Proteins of CTGF were detected using the Powervision two-step immunostaining method. RESULTS: Of the specimens from 122 GC patients analyzed for CTGF expression, 58 (58/122, 47.5%) had a high CTGF expression in cytoplasm of gastric carcinoma cells and 64 (64/122, 52.5%) had a low CTGF expression. Patients with a high CTGF expression showed a higher incidence of lymph node metastasis than those with a low CTGF expression (P = 0.032). Patients with a high CTGF expression had significantly lower 5-year survival rate than those with a low CTGF expression (27.6% vs 46.9%, P = 0.0178), especially those staging I + II + III (35.7% vs 65.2%, P = 0.0027). CONCLUSION: GC patients with an elevated CTGF expression have more lymph node metastases and a shorter survival time. CTGF seems to be an independent prognostic factor for the successful differentiation of high-risk GC patients staging I + II + III. Over-expression of CTGF in human GC cells results in an increased aggressive ability.

[Effects of enterostomy in treating locally advanced rectal cancer with combined chemoradiotherapy and operation].

OBJECTIVE: To investigate the effect of enterostomy in treatment of locally advanced rectal carcinoma patients with combined chemoradiotherapy and operation. METHODS: Clinical data from 51 cases of locally advanced rectal cancer patients treated with preoperative chemoradiotherapy and operation were analyzed. RESULTS: Thirty-three patients (64.9%) got staging down of their cancer after preoperative chemoradiotherapy, and 21.6% of patients (11 cases) had complete pathologic response. Thirty-seven patients received enterostomy, including extraperitoneal sigmoidostomy (29 cases), defunctioning ileostomy (8 cases) and double colostomy (3 cases with colon obstruction during preoperative therapy). One case experienced parastomal hernia and one stomal stenosis and 2 cases parastomal infection after enterostomy. No death of enterostomy occurred. CONCLUSION: Colostomy can reduce the pressure of obstructed intestinal tract and contribute much to the preoperative chemoradiotherapy, ileostomy can protect the distal stoma from leakage in sphincter saving operation. Enterostomy could be selected when needed in the favor of locally advanced rectal cancer patients.

[Preoperative chemoradiotherapy as neoadjuvant therapy for 35 patients with locally advanced lower rectal carcinoma].

OBJECTIVE: To explore the effect of combined preoperative chemotherapy with radiotherapy on locally advanced lower rectal carcinoma. METHODS: Thirty- five patients with locally advanced lower rectal carcinoma were received a new regimen of combined preoperative chemotherapy with radiotherapy. Routine fr action of radiation was given with total dose of 46 Gy,2 Gy per fraction,five ti mes a week. Patients received oxaliplatin 130 mg/m(2) (infusion) on day 1, plus leu novorin 200 mg/m(2) and 5- FU 500 mg/m(2)(intravenous bolus) from day 1 to day 3 eve ry 3 weeks for total two cycles before irradiation. Operation was performed 4 to 6 weeks later after neoadjuvant therapy. RESULTS: After neoadjuvant therapy,all patients underwent surgical resection with complete pathologic response in 7 patients,average tumor size decrease of in 34.4%, tumor stage decrease in 65.7% o f patients and nodal- negative change rate of 55.6%. Radical resection was per formed in 34 patients,in whom 18 patients received abdominoperineal resection(AP R) and 16 patients received sphincter- preserving surgery with 45.7% of anal preservation rate. One patient received palliative resection. No local recurrence occurred in all patients who received radical resection,but two cases had liver metastasis. CONCLUSION: Combined preoperative chemotherapy with radiotherapy is a better neoadjuvant therapy for lower advanced rectal cancer,which can decrease tumor stage,improve resectability and anal sphincter preservation rate,therefore ,this new neoadjuvant therapy with tolerable toxicity will has a promising application in the clinical setting.