Nong Xu

Celastrol induces apoptosis in non-small-cell lung cancer A549 cells through activation of mitochondria- and Fas/FasL-mediated pathways.

Celastrol is a natural compound extracted from the traditional Chinese medicinal herb, Tripterygium wilfordii Hook. It has attracted interests for its potential anti-inflammatory and antitumor effects. However, the molecular mechanisms of celastrol-induced apoptosis in cancer cells remain unclear. In this study, we investigated the effects of celastrol on the human non-small-cell lung cancer (NSCLC) cell line A549 in vitro. Celastrol caused a dose- and time-dependent growth inhibition of A549 cells with an IC(50) of 2.12 μM at 48 h treatment. Celastrol induced A549 cells apoptosis as confirmed by annexin V/propidium iodide staining and DNA fragmentation. Celastrol-induced apoptosis was characterized by cleavage of caspase-9, caspase-8, caspase-3, and PARP protein, increased Fas and FasL expression, and a reduction in the mitochondrial membrane potential. Furthermore, celastrol induced the release of cytochrome c. Celastrol also up-regulated the expression of pro-apoptotic Bax, down-regulated anti-apoptotic Bcl-2, and inhibited Akt phosphorylation. These results demonstrate that celastrol can induce apoptosis of human NSCLC A549 cells through activation of both mitochondria- and FasL-mediated pathways.

Prognostic significance of vascular endothelial growth factor immunohistochemical expression in gastric cancer: a meta-analysis

Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis, and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF protein overexpression with the clinical outcome in patients with gastric cancer, but yielded conflicting results. The prognostic significance of VEGF overexpression in gastric cancer remains controversial. Electronic databases updated to July 2011 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF overexpression and survival of patients with gastric cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 30 studies (nxa0=xa03,999 patients) that evaluated the correlation between VEGF overexpression detected by immunohistochemistry and survival in patients with gastric cancer. Combined hazard ratios suggested that VEGF-A overexpression had an unfavorable impact on overall survival (OS) (HR [hazard ratio]xa0=xa01.49, 95xa0% CI [confidence interval]: 1.22–1.77) and disease free survival (DFS) (HRxa0=xa01.85, 95xa0% CI: 1.38–2.32) in patients with gastric cancer. However, VEGF-C overexpression did not significantly correlate with OS (HRxa0=xa01.24, 95xa0% CI: 0.92–1.56) or DFS (HRxa0=xa01.15, 95xa0% CI: 0.78–1.52). VEGF-D is an unfavorable indicator of OS (HRxa0=xa01.68, 95xa0% CI: 1.02–2.34) and DFS (HRxa0=xa01.88, 95xa0% CI: 1.07–2.70) in patients with gastric cancer. VEGF-A and VEGF-D overexpression indicated a poor prognosis for patients with gastric cancer. VEGF-C overexpression was not associated with poor prognosis in patients with gastric cancer. The prognostic value of VEGF on survival still needs further larger prospective trials to be confirmed.

RRM1 and ERCC1 expression in peripheral blood versus tumor tissue in gemcitabine/carboplatin-treated advanced non-small cell lung cancer

PurposeTo comparatively evaluate the prognostic or predictive value of ribonucleotide reductase M1 (RRM1) and excision repair cross-complementation 1 (ERCC1) gene expression in peripheral blood versus tumor tissue from patients with advanced non-small cell lung cancer (NSCLC) treated by gemcitabine/platinum chemotherapy.MethodsA total of 49 patients with advanced NSCLC receiving gemcitabine plus carboplatin chemotherapy were studied. RRM1 and ERCC1 mRNA levels in the peripheral blood and tumor tissue were determined by real-time fluorescent quantitative PCR. The relationships between gene expression and clinical and pathological factors, response to chemotherapy as well as prognosis, were evaluated.ResultsRRM1 expression in peripheral blood and tumor tissue, but not ERCC1 expression, was found to be positively correlated (rxa0=xa00.332, 0.258; Pxa0=xa00.020, 0.073; respectively). RRM1 and ERCC1 expression levels were nearly synchronous in both peripheral blood (rxa0=xa00.351; Pxa0=xa00.013) and tumor tissue (rxa0=xa00.634; Pxa0<xa00.001). Neither was correlated with clinical and pathological factors. Patients with low RRM1 expression in peripheral blood or low RRM1 or ERCC1 expression in tumor tissue experienced better response to chemotherapy (50.0 vs. 16.0%, 50.0 vs. 16.0%, and 54.2 vs. 12.0%; Pxa0=xa00.012, 0.012, and 0.003; respectively), longer median survival (18.5 vs. 13.0xa0months, 18.5 vs. 12.0xa0months, and 19.8 vs. 12.5xa0months; Pxa0=xa00.043, 0.014 and 0.007; respectively), and longer progression-free survival (6.0 vs. 4.0xa0months, 7.8 vs. 3.9xa0months, and 5.8 vs. 3.8xa0months; Pxa0=xa00.044, 0.016, and 0.008; respectively). Cox multivariate regression analysis showed that ERCC1 expression in tumor tissue was independent indicator for overall survival.ConclusionsAdvanced NSCLC patients with low RRM1 mRNA expression both in peripheral blood and in tumor tissue could benefit from gemcitabine/carboplatin chemotherapy. ERCC1 mRNA expression in tumor tissue may be a predictive and prognostic indicator in advanced NSCLC patients receiving gemcitabine/carboplatin chemotherapy.

Prognostic Value of Perineural Invasion in Gastric Cancer: A Systematic Review and Meta-Analysis

Background The prognostic role of perineural invasion in gastric cancer is controversial. Here, we present a systemic review and meta-analysis of the association between perineural invasion and survival in resectable gastric cancer patients. Methods A comprehensive literature search for relevant reports published up to April 2013 was performed using PubMed, Embase, Web of Science and Wanfang Data. Studies that investigated the role of perineural invasion with a sample size greater than 100 were included and analyzed. Results A total of 30,590 gastric cancer patients who had undergone curative gastrectomy from twenty-four studies were included. The median rate of perineural invasion positive was 40.9% (6.8%–75.6%). Fourteen studies investigated overall survival unadjusted for other variables in 23,233 gastric cancer patients. The relative hazard estimates ranged from 0.568–7.901 with a combined random effects estimate of 2.261 (95% CIu200a=u200a1.841–2.777, Pu200a=u200a0.000). The effect of perineural invasion on overall survival adjusted for other prognostic factors was reported in 17 studies incorporating 8,551 cases. The hazard estimates ranged from 0.420–8.110 with a pooled random effects estimates of 1.484 (95% CIu200a=u200a1.237–1.781, Pu200a=u200a0.000). There was heterogeneity between the studies (Qu200a=u200a49.22, I-squaredu200a=u200a67.5%, Pu200a=u200a0.000). Disease-free survival was investigated adjusted in four studies incorporating 9,083 cases and the pooled fixed hazard ratio estimate was 1.371(95% CIu200a=u200a1.230–1.527, Pu200a=u200a0.000). Conclusion Perineural invasion is an independent prognostic factor affecting overall survival and disease-free survival of gastric cancer patients who had undergone the curative resection. This effect is independent of lymph node status, tumor size and the depth of invasion as well as a range of other biological variables on multivariate analysis. Large prospective studies are now needed to establish perineural invasion as an independent prognostic marker for gastric cancer.

Phase II study of epirubicin plus oxaliplatin and infusional 5-fluorouracil as first-line combination therapy in patients with metastatic or advanced gastric cancer

The purpose of this study was to evaluate the efficacy and safety of an epirubicin, oxaliplatin and infusional 5-fluorouracil combination in patients with advanced gastric cancer. Patients with previously untreated advanced measurable gastric cancer received epirubicin (50u2009mg/m2, day 1), oxaliplatin (130u2009mg/m2 2-h infusion, day 1) and 5-fluorouracil (750u2009mg/m2, 24-h infusion, day 1–3) every 3 weeks. The primary endpoint of this phase II study was the response rate according to Response Evaluation Criteria in Solid Tumors. Out of 48 patients, 46 were evaluable for efficacy and 48 for toxicity. A median of five cycles (range 1–6) was administered. The overall best response rate was 47.8% (95% confidence interval 33–63%) including 2.2% complete responses and 45.6% partial responses. The median time for progression and median overall survival was 5 (95% confidence interval 4.1–5.9) and 11 months (95% confidence interval 8.1–13.9), respectively. Grade 3/4 neutropenia and leukocytopenia were observed in 25 and 12.5% of patients, respectively. Grade 3/4 nonhematological toxicities included nausea (6.3%), vomiting (14.6%), neurological toxicity (10.4%) and mucositis (2.1%). The epirubicin, oxaliplatin and infusional 5-fluorouracil regimen was effective and well tolerated as a front-line chemotherapy for patients with metastatic or advanced gastric cancer, and should be evaluated further.

New EGFR-TKI: a case report of recurrent lung adenocarcinoma successfully treated with icotinib

Icotinib is a new oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). We report on a 49-year-old man with recurrent lung adenocarcinoma treated with icotinib. The patient obtained a partial remission in 4 weeks that was maintained 14 months. Retrospective examination of EGFR mutations confirmed he had a sensitive mutation (exon 19 deletion). This case supports that icotinib has great efficacy in advanced non-small cell lung cancer with sensitive EGFR mutations.

Phase II trial of gefitinib in pretreated Chinese women with advanced non-small-cell lung cancer.

A phase II clinical trial was performed to evaluate the efficacy and safety of gefitinib on pretreated Chinese female non-small-cell lung cancer (NSCLC) patients. Chinese female patients with locally advanced or metastatic NSCLC who failed at least one platinum-based chemotherapy received gefitinib monotherapy (250xa0mg/day) between April 2002 and January 2010. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS) and progression-free survival (PFS). Of the 40 evaluable female patients, the ORR was 62.5%. All patients have responded with one (2.5%) complete response, 24 (60%) partial response, 12 (30%) stable disease, and 3 (7.5%) progressive disease. The OS and PFS were 20xa0months (95% CI: 11.9–28xa0months) and 13xa0months (95% CI: 8.0–17.9xa0months), respectively. Survival (OS and PFS) were longer in patients with good performance status and in patients older than 65xa0years (Pxa0<xa00.05). The most frequently observed toxicities were rash/dry skin (80%), diarrhea (42.5%), and vomiting/anorexia (32.5%). Four patients developed grade 3 toxicities (rash and diarrhea) but did not require either dose reduction or discontinuation. Gefitinib is a highly effective and well-tolerated agent for Chinese women with pretreated advanced NSCLC.

Complete remission of platinum-refractory primary Fallopian tube carcinoma with third-line gemcitabine plus cisplatin: A case report and review of the literature

Primary Fallopian tube carcinoma (PFTC) is a rare but highly aggressive disease. Currently, treatments are similar to those used in epithelial ovarian carcinoma (EOC), however, there are distinct differences between the two diseases. PFTC tends to recur in the retroperitoneal nodes and distant sites more often than EOC. Limited literature with regard to effective agents in platinum-resistant and -refractory (Pt-R) disease exists, particularly after two lines of consecutive treatment. In this case report, a 47-year-old female with PFTC exhibited recurrence in the liver after postoperative chemotherapy. The patient received paclitaxel and cisplatin combination as first-line chemotherapy and topotecan as a second-line treatment, which is considered platinum-refractory. After the second-line treatment failed, this patient received a gemcitabine plus cisplatin combination as third-line chemotherapy for a total of 6 cycles. The liver metastases regressed rapidly and completely. The patient’s progression-free survival (PFS) was 10 months and overall survival (OS) was 45 months. In conclusion, gemcitabine and cisplatin combination is an effective regimen for refractory PFTC even after the failure of two previous lines of consecutive chemotherapy and this warrants further independent investigation.

Phase II study of FOLFIRI regimen in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.

PurposeTo evaluate the efficacy and safety of FOLFIRI regimen in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.MethodsThe FOLFIRI regimen consisted of intravenous infusion of irinotecan 180xa0mg/m2 on day 1 plus leucovorin (LV) 400xa0mg/m2 on day 1 plus 5-fluorouracil (5-FU) 400xa0mg/m2 bolus on day 1 plus 46-hour intravenous infusion of 5-FU 2,400xa0mg/m2, every 2xa0weeks as one cycle. The main selection criterion for this study was the advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.ResultsOf the 57 evaluable patients for efficacy, 4 (7.5%) had a partial response, 36 (67.9%) had stable disease, and 13 (24.5%) had progressive disease. Median progression-free survival was 4.8xa0months (95% CI 3.9–5.7xa0months), and median overall survival was 7.8xa0months (95% CI 13.1–16.5xa0months). Safety analysis was based on the data of 57 evaluable patients. The most frequently observed grade 3 or 4 toxicities were neutropenia 16 (27.8%), nausea/vomiting 7 (12.3%), and diarrhea 1 (1.8%).ConclusionFOLFIRI regimen is effective and well tolerated in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin in Chinese population.

Bone marrow metastasis of desmoplastic small round cell tumor.

Desmoplastic small round cell tumor is an extremely rare and highly aggressive neoplasm. It usually arises as a single mass or multiple masses in the abdominal cavity, characterized by diffuse peritoneal implants, involvement of regional lymph nodes, and liver and lung metastases. However, bone marrow metastasis has rarely been reported in the literature. We present a case of clinically symptomatic bone marrow metastasis in a 25-year-old woman with a diagnosis of desmoplastic small round cell tumor originating from the pelvic cavity.