Jingzhu Zhao

A retrospective clinicopathologic study of remnant gastric cancer after distal gastrectomy.

Introduction:Remnant gastric cancer (RGC) is a unique clinical entity with relatively less frequency in gastric cancer series and often reported to be detected at advanced stages and had poor prognosis. Methods:A total of 112 patients with RGCs from July 1991 to July 2008 were enrolled in this retrospective analysis. Results:A total number of 112 cases were composed of 20 (17.8%) differentiated carcinomas and 92 (82.2%) undifferentiated carcinomas. There are 64 (57.1%) patients with tumor at anastomotic site and 48 (42.9%) tumor at nonanastomotic site. The diameter of tumors was ≥4 cm in 83 (74.1%) patients. Borrmann III, IV accounted for 70.5% and 17.8% respectively. Three (2.6%) patients were classified as stage I, 16 as stage II (14.2%), 62 as stage III (55.3%), and 31 (27.6%) as stage IV. Percentage of T4 stage was 57.1%. Distant metastasis rate and lymph node metastasis rate were 27.6% and 58.9%, respectively. There were numerous clinicopathologic differences according to different original disease, initial reconstruction, and tumor location. The median overall survival time was 27.9 months. TNM stage and option of treatments were independent prognostic factors in multivariable analysis. Conclusions:The lifelong annual follow-up endoscopic examinations after the initial gastrectomy and radical resection may help to improve the prognosis of RGCs.

miR-24 promotes the proliferation, migration and invasion in human tongue squamous cell carcinoma by targeting FBXW7.

Recent studies suggest that aberrant expression of miR-24 is linked to various human cancers, including tongue squamous cell carcinoma (TSCC). F-box and WD-40 domain proteinxa07 (FBXW7), a tumor-suppressor gene, is responsible for the degradation of several proto-oncogenes. However, the function and mechanism of miR-24 and FBXW7 in TSCC remains unclear. In the present study, we found that miR-24 was increased in TSCC tissues and cell lines, and that upregulation of miR-24 was associated with advanced clinical stage and a shorter overall survival of TSCC patients. Inhibition of miR-24 significantly suppressed the proliferation, migration and invasion of TSCC cells inxa0vitro. Furthermore, miR-24 repressed FBXW7 expression by directly binding to the 3-untranslated region of FBXW7. Moreover, the suppression of FBXW7 increased the proliferation, migration and invasion of TSCC cells, and the restoration of FBXW7 substantially attenuated the oncogenic effects of miR-24. In conclusion, our results demonstrated that upregulation of miR-24 was associated with tumor progression and poor prognosis in TSCC patients, and that overexpression of miR-24 was correlated with the proliferation, migration and invasion of TSCC cells inxa0vitro, at least partially through regulation of its functional target FBXW7. Thus, miR-24 may serve as a novel potential biomarker for the prognosis of TSCC patients.

Immunoactivative role of indoleamine 2,3‑dioxygenase in gastric cancer cells in vitro

To study the role of indoleamine 2,3-dioxygenase (IDO) in immune response and immune escape in gastric cancer, the human IDO gene was cloned by reverse transcription-polymerase chain reaction (RT-PCR) and inserted into the pIRES2-EGFP vector to construct the IDO expression vector (pIRES2-EGFP-IDO). BGC-823 cells were transfected with the vector by electroporation and selected stable expression with G418. IDO expression was determined by RT-PCR and Western blot analysis. The enzymatic activity of IDO was estimated by determining tryptophan and kynurenine concentrations in the cell culture medium by an amino acid analyzer. To assess the effect of IDO on T cell-mediated cytotoxicity and proliferation, T cells from patients with gastric cancer were co-cultured with the IDO-transfected BGC-823 cells in the presence or absence of 1-MT, a competitive inhibitor of IDO. Cells transfected with the vector expressed high levels of IDO mRNA and protein, and a significantly higher level of kynurenic acid was detected in the culture medium of the transfected cells compared to the non-transfected cells (P<0.001). T cells co-cultured with the IDO-transfected cells exhibited significantly lower cytotoxicity compared to the control group (P<0.05). Additionally, IDO-transfected cells treated with 1-MT exhibited higher toxicity compared to the untreated IDO-transfected cells (P<0.01). We conclude that IDO plays a key role in gastric cancer immune suppression, possibly by inhibiting T cell-mediated cytotoxicity and proliferation in vitro.

Aurora-A-mediated phosphorylation of LKB1 compromises LKB1/AMPK signaling axis to facilitate NSCLC growth and migration

Deletion or loss-of-function mutation of LKB1, frequently occurring in non-small cell lung cancers (NSCLCs), is a predominant caution of NSCLC initiation and progression. However, the upstream signaling pathways governing LKB1 activation are largely unknown. Here, we report that LKB1 undergoes Aurora kinase A (AURKA)-mediated phosphorylation, which largely compromises the LKB1/AMPK signaling axis, in turn leading to the elevation of NSCLC cell proliferation, invasion and migration. Mechanically, AURKA-mediated phosphorylation of LKB1 impairs LKB1 interaction with and phosphorylation of its downstream target AMPKα, which has critical roles in governing cancer cell energy metabolic homeostasis and tumorigenesis. Clinically, AURKA displays high levels in NSCLC patients, and correlates with poor outcome of patients with lung adenocarcinoma. Pathologically, the amplification or activation of AURKA-induced impairment of the LKB1/AMPK signaling pathway contributes to NSCLC initiation and progression, highlighting AURKA as a potential therapeutic target for combatting hyperactive AURKA-driven NSCLCs.

Suberoyl bis-hydroxamic acid activates Notch1 signaling and induces apoptosis in anaplastic thyroid carcinoma through p53

Anaplastic thyroid cancer (ATC), usually derived from well-differentiated thyroid cancers is one of the most lethal human endocrine malignancies. In the present study, we report that in human ATC tumor tissue samples exist undetectable Notch1 and the active Notch1 intracellular domain could not be detected in ATC-CAL-62 cells. Interesting, suberoyl bis-hydroxamic acid (SBHA) administration could induce Notch1 intracellular domain levels in a dose-dependent manner, coupled with the increase of p53 and p21. Furthermore, ectopic expression of Notch1 or deletion of p53 with small-interfering RNA was able to abolish the effects of SBHA to elevation of Notch1 and p53 in ATC cells. As a result, SBHA treatment efficiently induced ATC cell apoptosis. These results indicate that SBHA may play antitumor functions via regulating Notch1/p53 signals, and highlight that SBHA could have clinical potential to benefit the therapy of ATC patients.

Loss of PTEN Expression Is Associated With High MicroRNA 24 Level and Poor Prognosis in Patients With Tongue Squamous Cell Carcinoma

PURPOSEnThe aim of this study was to detect the relationship between phosphatase and tensin homolog deletion on chromosome 10 (PTEN) and microRNA 24 (miR-24) and correlate PTEN expression with important clinical parameters of patients with tongue squamous cell carcinoma (TSCC).nnnMATERIALS AND METHODSnIn this retrospective case series, all TSCC patients treated at Tianjin Medical University Cancer Institute and Hospital between March 2005 and October 2011 were retrospectively reviewed. Demographic information and clinical data (histologic type, clinical stage, tumor differentiation, and so on) were collected. The miR-24 level was detected by quantitative reverse transcription-polymerase chain reaction. The PTEN level was analyzed by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. Data analyses were performed by Spearman correlation analysis, Pearson χ2 test, and paired t test. Kaplan-Meier curves, log-rank analyses, and a Cox proportional hazards model were used to evaluate the prognostic value of PTEN.nnnRESULTSnA total of 90 patients (aged 59.4xa0±xa09.5xa0years, 53 men and 37 women) were identified.nLoss of PTEN expression was detected in 27 of 90 tumors (30%)” in both occurrences [corrected].nThe PTEN messenger RNA level was negatively correlated with the miR-24 level (rxa0=xa0-0.569, Pxa0<xa0.01). PTEN expression also was negatively correlated with the miR-24 level (rxa0=xa0-0.621, Pxa0<xa0.01). Furthermore, PTEN expression was significantly lower in cancer tissues than in adjacent normal tissues, and its expression was negatively correlated with clinical stage (Pxa0<xa0.01) and positively correlated with differentiation (Pxa0<xa0.05) in TSCC patients. In addition, the Kaplan-Meier curve indicated that loss of PTEN expression resulted in poor survival of TSCC patients (Pxa0<xa0.01). Multivariate analysis indicated that PTEN expression level and clinical stage may be independent prognostic factors for TSCC patients.nnnCONCLUSIONSnThis study suggested that PTEN expression was negatively correlated with the miR-24 level in TSCC. The loss of PTEN expression may serve as a predictor of unfavorable prognosis for TSCC patients.