Association of cytoplasmic p27 expression with an unfavorable response to cisplatin-based chemotherapy and poor outcomes in non-small cell lung cancer.

Reduced nuclear p27 expression is associated with a poor outcome in various cancers, including non-small cell lung cancer (NSCLC). Cytoplasmic p27 expression was shown to be associated with an unfavorable response to chemotherapy and poor outcomes in some carcinomas, but it has not been well studied in NSCLC. Herein, p27 expression in 219 tumors surgically resected from NSCLC patients was evaluated by immunohistochemistry (IHC). The most common of p27 immunostaining in lung tumors was observed in the cytoplasm (N-/C+, 32 %), followed by negative (N-/C-, 29 %), nucleus (N+/C-, 24 %), and nucleus plus cytoplasm (N+/C+, 15 %). Kaplan-Meier and Cox regression models showed that p27 N-/C+ tumors exhibited the worst overall survival (OS) and relapse-free survival (RFS) among the four categories of tumors. Among 135 of 219 patients who received cisplatin-based chemotherapy, p27 N-/C+ tumors most commonly showed an unfavorable response to cisplatin-based chemotherapy, followed by p27 N-/C- tumors when p27 N+/C- tumors were used as a reference. IHC analysis for phosphorylated extracellular signal-regulated kinase (p-ERK) and Bcl-2 expression in the lung tumors was performed to test whether ERK activation could enhance p27 nuclear export and the expression of Bcl-2 to test whether ERK activation could enhance p27 nuclear export and Bcl-2 expression. The data showed that p-ERK expression was positively correlated with cytoplasmic p27 (N-/C+) and Bcl-2 expression in the lung tumors. Patients with high Bcl-2-expressing tumors treated with cisplatin-based chemotherapy showed unfavorable predictive values in a subset of this study population. Therefore, we suggest that cytoplasmic p27 (N-/C+) via ERK-activated Bcl-2 expression may predict an unfavorable response to cisplatin-based chemotherapy and poor outcomes in NSCLC.

MicroRNA-184 Deregulated by the MicroRNA-21 Promotes Tumor Malignancy and Poor Outcomes in Non-small Cell Lung Cancer via Targeting CDC25A and c-Myc.

BACKGROUND: MicroRNA (miR)-184 has been reported to have a dual role in human cancers. However, the role of miR-184 in non-small cell lung cancer (NSCLC) remains unclear. METHODS: Wild-type or mutant CDC25A promoters were constructed by PCR and site-directed mutagenesis to verify whether miR-184 could inhibit CDC25A expression at post-transcription level. Boyden chamber assay was used to assess whether miR-184 could modulate cell invasiveness via targeting CDC25A and c-Myc. We utilized 124 tumors from NSCLC patients to determine miR-184, miR-21, PDCD4 mRNA, c-Myc mRNA, and CDC25A mRNA expression levels by means of real-time PCR analysis. The prognostic value of CDC25A, c-Myc, and miR-184 on overall survival (OS) and relapse-free survival (RFS) was evaluated by Kaplan-Meier and Cox regression analysis. RESULTS: MiR-184 suppressed CDC25A expression by enhancing the instability of its mRNA as a result of miR-184 binding to its coding region. An increase in CDC25A expression by means of a reduction in miR-184 promotes cell invasiveness. Moreover, a concomitant increase in CDC25A and c-Myc expression as a result of decreased miR-184 via the miR-21-mediated PDCD4 reduction is responsible for cell invasiveness. Among patients, miR-184 expression in lung tumors was found to correlate negatively with CDC25A mRNA, c-Myc mRNA, and miR-21 expression, but was positively related to PDCD4 mRNA expression. High-miR-184, High-CDC25A, or high-c-Myc mRNA tumors exhibited shorter OS and RFS periods than their counterparts. The worst OS and RFS were observed in low-miR-184/high-CDC25A/high-c-Myc tumors, followed by low-miR-184 /high-CDC25A, low-miR-184/high-c-Myc, high-c-Myc, and high-CDC25A tumors. CONCLUSIONS: MiR-184 as a tumor suppressor miR inhibits cell proliferation and invasion capability via targeting CDC25A and c-Myc. Low miR-184 level may predict worse prognosis in NSCLC patients.

Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil-based chemotherapy in colorectal cancer.

Natural products, such as fermented soybeans, have been used to treat various physical conditions, including cancer. MB-6 is a botanical preparation composed of fermented soybean extract, green tea extract, Antrodia camphorata mycelia, spirulina, grape seed extract, and curcumin extract. Based on this, we hypothesized that MB-6 would increase the effectiveness of chemotherapy in patients with colon cancer. In a rodent study, MB-6, in combination with leucovorin/5-fluorouracil chemotherapy, increased the survival rate and life span of colon cancer tumor-bearing BALB/c mice as compared with treatment with chemotherapy alone. In a proof-of-concept clinical study, 72 patients with metastatic colorectal cancer were randomized to receive leucovorin, 5-fluorouracil, and oxaliplatin in combination with either MB-6 or placebo for 16 weeks. The primary outcome was the best overall response, and secondary outcomes included progression-free survival, overall survival, and adverse effects. Up to 77 weeks after treatment, there was follow-up with the patients. No significant difference in the best overall response rate and overall survival was observed between the 2 groups. Patients in the MB-6 group had a significantly lower disease progression rate than patients in the placebo group, during the study period (0.0% vs 15.8%, P = .026). The placebo group had a significantly higher incidence of adverse events at least grade 4 compared with the MB-6 group (28.9% vs 2.9%, respectively, P = .004) and a significantly higher occurrence of increased serum creatinine compared with the MB-6 group (29% vs 5.9%, P = .014). MB-6 is a promising botanical supplement that may increase the effectiveness of chemotherapy in patients with metastatic colorectal cancer.

Missed cancerous lesions in emergency laparoscopic surgery: retrospective study of 2074 cases.

Abdominal laparoscopy is a widely accepted surgical procedure effective even for acute abdominal ailments. However, one major concern in using abdominal laparoscopy is missed lesions, in the past this has not been adequately explored. The aim of this retrospective study, therefore, is to evaluate cancerous lesions that are missed during emergency laparoscopic surgeries. The medical records of 2074 patients who had a laparoscopy from March 1996 to April 2006 for acute abdomen symptoms, including diagnostic laparoscopy (n = 119), laparoscopic appendectomy (n = 1336), laparoscopic duodenorrhaphy (n = 30), and laparoscopic cholecystectomy (n = 589) were reviewed. Missed cancerous lesions included cecal cancer (n = 2), sigmoid cancer (n = 1), and jejunum lymphoma (n = 1). The incidence of missed cancerous lesions in an emergency laparoscopic surgery is 0.19%, mainly due to its lower tactile sensitivity compared to the direct hand palpation and masqueraded by inflammatory process. Therefore, careful observation is recommended for post-emergency laparoscopic patients and follow-up should be performed within three months, especially for patients with intra-abdominal and/or severe inflammation status.