Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression.

BACKGROUND: Long non-coding RNAs play an important role in tumorigenesis, hence, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. Recently, the downregulation of lncRNA MEG3 has been observed in various human cancers. However, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of this study was to examine the expression pattern of MEG3 in NSCLC and to evaluate its biological role and clinical significance in tumor progression. METHODS: Expression of MEG3 was analyzed in 44 NSCLC tissues and 7 NSCLC cell lines by qRT-PCR. Over-expression approaches were used to investigate the biological functions of MEG3 in NSCLC cells. Bisulfite sequencing was used to investigate DNA methylation on MEG3 expression. The effect of MEG3 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by Hoechst staining and Flow-cytometric analysis. NSCLC cells transfected with pCDNA-MEG3 were injection into nude mice to study the effect of MEG3 on tumorigenesis in vivo . Protein levels of MEG3 targets were determined by western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed). RESULTS: MEG3 expression was decreased in non-small cell lung cancer (NSCLC) tumor tissues compared with normal tissues, and associated with advanced pathologic stage, and tumor size. Moreover, patients with lower levels of MEG3 expression had a relatively poor prognosis. Overexpression of MEG3 decreased NSCLC cells proliferation and induced apoptosis in vitro and impeded tumorigenesis in vivo. MDM2 and p53 protein levels were affected by MEG3 over-expression in vitro. CONCLUSIONS: Our findings indicate that MEG3 is significantly down-regulated in NSCLC tissues that could be affected by DNA methylation, and regulates NSCLC cell proliferation and apoptosis, partially via the activition of p53. Thus, MEG3 may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention.

[Effect of neoadjuvant chemoradiotherapy on the healing of anastomosis following low anterior resection in locally advanced rectal cancer].

OBJECTIVE: To investigate the effect of the neoadjuvant chemoradiotherapy (NCR) on the healing of anastomosis following low anterior resection in patients with locally advanced rectal cancer. METHODS: Between May 2001 and August 2007, 192 patients with T3 and T4 low rectal cancer (distance from the tumor to anal verge 0.05). Anastomotic leakage occurred in 2 - 10 days post operation, and were managed properly and got desirable results. CONCLUSION: Neoadjuvant chemoradiotherapy would not affect the healing of anastomosis obviously if being applied reasonably in locally advanced low rectal cancer.

[Exploration on neoadjuvant chemoradiation in the treatment for locally advanced low rectal cancer].

OBJECTIVE: To explore the possibility of further improvement of the efficacy of neoadjuvant chemoradiotherapy in locally advanced lower rectal cancer and the management of patients with clinical complete regression. METHODS: From May 2001 to August 2007, 192 cases with locally advanced lower rectal cancer (T3/T4 or N(+)) received preoperative radiotherapy 40 - 46 Gy/20 - 23 fractions and concomitant oral capecitabine 625 mg/m(2) bid for 10 weeks prior to surgery. Curative resection with total mesorectal excision (TME) was carried out 6 weeks after the end of radiation. RESULTS: As a result, 117 cases (60.9%) experienced adverse events but only 2 suffered from G3 side effects. Seventeen cases (8.9%) had a clinical complete tumor regression without surgery; 175 patients underwent curative resection, of them 134 cases with low anterior resection (LAR), 32 cases with ultra-low anterior resection with Park's coloanal anastomosis (6 cases with diverting temporary colostomy) and 9 cases with abdominal pelvic resection (APR). Sphincter preservation was achieved in 94.9%. Twenty-four patients (12.5%) got pathological complete response (CR), 17 patients with clinical CR and the overall CR rate was 21.4%. According to the pathological staging post operation: T0N0 41 cases, T2N0 43 cases, T3N0 77 cases, T4N0 5 cases, T2N1 11 cases, T3N1 13 cases, T4N1 2 cases; Graded under Dworak's tumor regression: TRG0 8 patients, TRG1 32 patients, TRG2 28 patients, TRG3 83 patients and TRG4 24 patients, with an overall pathological tumor downstaging in 77.14%. No operative death occurred, 5 patients suffered from rectovaginal fistulas and 4 anastomotic leakages with an overall anastomotic leakage rate of 5.1% (9/175) and all the patients recovered uneventfully after properly managed. All patients were followed up for a median time of 42 months (range, 12 - 87 months). During the time, 11 patients developed lung metastases, 6 liver metastases and 7 had local recurrences. The 3 years disease-free survival (DFS) was 86.6% and overall survival (OS) was 92.6%. CONCLUSIONS: Neoadjuvant chemoradiotherapy has high efficacy in locally advanced lower rectal cancer, resulting in tumor down-staging, improved resectability and sphincter preservation, and reduced local recurrences. Meanwhile the cases with clinical complete response can be followed up closely and safely without surgery.

[Efficacy of neoadjuvant radiochemotherapy in treatment of locally advanced low rectal cancer].

OBJECTIVE: To explore efficacy of neoadjuvant radiochemotherapy in locally advanced low rectal cancer. METHODS: From May 2001 to August 2005, 105 patients with locally advanced low rectal cancer (T3, T4) were treated by preoperative radiotherapy to pelvis, 2.0 Gy daily up to 40-46 Gy in 4-5 weeks concomitantly with oral capecitabine at 1250 mg x m(-2) x d(-1) for 10 weeks up to surgery. In all patients surgery was carried out under the rule of total mesorectal excision technique. RESULTS: All patients finished the course of neoadjuvant radiochemotherapy. Among them, 36 patients experienced adverse effects. Thirteen patients resulted in complete tumor response and spared the operation. Ninety-two patients were operated on with radical resection, among them 71 patients with low anterior resection, 17 with Parks' colo-anal anastomosis and 4 with abdomino-perineal resection, so sphincter preservation was achieved in 96.2%. In postoperative pathological studies, 11 cases showed complete tumor regression. According to the TNM staging system, 24 cases were ranged T0N0, and 23 cases T2N0, 43 cases T3N0, 2 cases T4N0, 5 cases T2N1, 8 cases T3N1; and according to Dworak's tumor regression grading, 5 cases were ranked TGR0, and 18 cases TGR1, 11 cases TGR2, 47 cases TGR3, 24 cases TGR4. Pathologic downstaging was achieved in 78.1%, including complete response (TGR4) and intermediate response (TGR2 + 3). No operative death occurred. Anastomotic leakage was found in 5 cases, including 3 rectovaginal fistula. All patients have been followed up for 16-67 months, and lung metastasis occurred in 4 cases, liver metastasis in 2 patients and local recurrence in 4 patients. Three patients died of distant metastasis. The 3-year disease-free survival was 82.8% and overall survival was 96.5%. CONCLUSIONS: Neoadjuvant radiochemotherapy brings tumor down-staging and increases resectability and sphincter preservation, decreases recurrence and improves survival in locally advanced low rectal cancer.

[Irinotecan combined with fluoropyrimidine in treatment for advanced/metastatic colorectal carcinoma].

OBJECTIVE: To explore the efficacy and safety of CPT-11 combined with fluoropyrimidine in treatment for advanced or metastatic colorectal carcinoma. METHODS: From January 2001 to September 2003, 43 patients with advanced or metastatic colorectal carcinoma were randomized into two groups, group A [CPT-11 90 - 25 mg/m(2) continuous infusion for 10 h and folinic acid (FA) 30 mg x m(-2) x d(-1) + 5-FU 425 mg x m(-2) x d(-1) x 2 d continuous infusion for 48 h, every two weeks as a cycle in total of no less than six cycles] and group B (CPT-11 90 - 125 mg/m(2) continuous infusion for 10 h every two weeks as a cycle in total of no less than six cycles and capecitabine 1250 mg x m(-2) x d(-1) by oral divided into two doses, continuously taken without interruption for three months). RESULTS: In this study, overall response rate (ORR) was 44.2%, disease control achieved in 83.7%, Time to progression (TTP) was 11.0 months and overall survival (OS) was 14.6 months. Response rate in group A was 31.3% and 51.9% in group B. TTP of group A was 8.4 months and that of group B was 12.5 months; OS in group A was 14.2 months and 17.9 months in group B. In 43 cases with 502 cycles of chemotherapy, grade III side effect occurred only in 3.0% and no therapy-related death occurred. Nausea and vomiting was the most common side effect with an occurrence rate of 31.9% in group A and 2 cases of grade III, and 22.7% in group B with no case of grade III. Occurrence of side effect was much lower in group B than that of group A except hand-foot syndrome, which was 16.1% in group B with 2 cases of grade III as compared to 1.4% in group A with no case of grade III. CONCLUSIONS: Combination of CPT-11 and fluoropyrimidine is effective and safe in treatment for advanced/metastatic colorectal carcinoma. CPT-11 combined with capecitabine are not only more effective, but also its occurrence of side effect is lowered, and are especially high effective for lung metastasis. There is reasonable to recommend that combination of CPT-11 with capecitabine may be as first choice in treatment for such cases.

[First-line Xeloda (Capecitabine) treatment for advanced and recurrent colorectal cancer].

OBJECTIVE: To evaluate the efficacy and safety of capecitabine as first-line therapy in patients with advanced and recurrent colorectal cancer. METHODS: From December 2000 to November 2001, sixty patients with advanced and recurrent colorectal cancer received first-line capecitabine treatment given at a dose of 1250 mg/m(2) twice daily, on days 1 - 14 every 21 days. At least 2 cycles were administered. RESULTS: The overall response rate was 23.3% with 14 PR, 24 SD (40.0%) and 15 PD. The median survival time was 14.7 months. The survival rate was 63.9% at 12-months and 33.4% at 24-months. Grade III-IV adverse effects were diarrhea in 4 patients (6.6%), anemia in 2 (3.3%) and hand-foot syndrome (HFS) in 1 (1.7%); Grade I-II adverse effects were hyperpigmentation in 20 (33.3%), HFS in 18 (30.0%) and diarrhea in 10 (16.7%). CONCLUSION: Capecitabine is an efficacious and better-tolerated alternative treatment for the patients with advanced and recurrent colorectal cancer.

Relationship between the depression status of patients with resectable non-small cell lung cancer and their family members in China.

PURPOSE: Less work on depression status has been done with family members of patients with non-small cell lung cancer (NSCLC). This study investigated depression status of patients and their family members; and the relationship of the depression status between these two groups. METHODS: This cross-sectional study enrolled 194 patients diagnosed with non-small cell lung cancer as well as their family members. In this study, a self-administered General Information Questionnaire was used to collect general information and the Self-rating Depression Scale (SDS) to assess depression status. Linear correlation analysis was used to probe the relationship of the depression status between patients and their family members. RESULTS: Of the 194 patients, 148 (76.3%) showed symptoms of depression. 148 (76.3%) family members had depression symptoms. The severity of depression in patients was positively correlated with that of family members (r = 0.577, p < 0.01). CONCLUSIONS: Patients with lung cancer and their family members suffered depression, and the two were correlated. A prospective study might prove helpful in determining the real relationship existing between the two groups' mental status and whether early detection and intervention might ameliorate this current situation.