Association of p16 as Prognostic Factors for Oropharyngeal Cancer: Evaluation of p16 in 1470 Patients for a 16 Year Study in Northeast China.

Human papillomavirus (HPV) is an etiological risk factor for oropharyngeal squamous cell carcinomas (OPSCC). Our study investigates the prevalence, prognostic, and clinicopathologic features of HPV-related oropharyngeal cancer in Northeast China and elucidates the involvement of p16 in the tumorigenesis and progression of OPSCC. Specimens from 1470 OPSCC patients collected from 2000 to 2016 were analyzed using the status of HPV by polymerase chain reaction (PCR) and p16 immunohistochemistry. Overexpression of p16 was observed in 81 (5.51%) of the 1470 cases, and HPV positive was present in 78 cases (5.31%) of the 1470 cases. HPV positive and p16 overexpression have a good concordance. However, we found that the etiological fraction of HPV in cancers of the OPSCCs was obviously lower in Northeast China than other cohorts previously reported. Interestingly, nearly 89% of patients with p16 expression were smokers, and nearly 70% of patients with p16 expression had a history of alcohol. Our study also demonstrates that p16 expression is significantly associated with early stage primary OPSCCs and the patients with p16 expression tend to show better survival following surgery and radiotherapy.

Panax ginseng polysaccharide induces apoptosis by targeting Twist/AKR1C2/NF-1 pathway in human gastric cancer.

In the present study, we isolated and screened an antitumor polysaccharide (PGP2a) from the roots of Panax ginseng. Chemical composition analysis indicated PGP2a was an acidic protein-polysaccharide. The average molecular weight was estimated to be 3.2 × 10(4)Da. According to gas chromatography (GC) result, PGP2a consisted of galactose, arabinose, glucose and galacturonic acid in the molar ratio of 3.7:1.6:0.5:5.4, respectively. MTT assay showed that PGP2a had a potent inhibitory effect on the growth of HGC-27 cells in a dose-dependent fashion. Furthermore, the number of HGC-27 cells arrested in G2/M phase, and the percentage of apoptotic cells were increased in response to PGP2a treatment along with concentration increasing. Moreover, western blotting analysis showed that protein expressions of Twist and AKR1C2 were suppressed by PGP2a, whereas an increase of NF1 was observed at protein level. Taken together, these findings suggested that PGP2a could be developed as a novel antitumor agent acting on Twist related gene for human gastric cancer therapy.

Astrocyte elevated gene-1: a novel independent prognostic biomarker for metastatic ovarian tumors.

Astrocyte elevated gene-1 (AEG-1), a novel tumor-associated gene, was found overexpressed in many tumors. Therefore, our purpose is to estimate whether AEG-1 overexpression is a novel predictor of prognostic marker in metastatic ovarian tumors. Immunohistochemistry was used to estimate AEG-1 overexpression in metastatic ovarian tumors from 102 samples. The association between AEG-1 expression and prognosis was estimated by univariate and multivariate survival analyses with Cox regression. The log-rank test was used to identify any differences in the prognosis between the two groups. The median overall and progression-free survival rates of patients with tumors from gastrointestinal tract origin were 0.97 and 0.51 years, respectively. Similarly, survival rates of patients with tumors of breast origin were 2.68 and 1.96 years (P < 0.0001). Of 102 patients, 77 had high expression, and AEG-1 overexpression had a significant link of prognosis in metastatic ovarian patients (P < 0.01). On the other hand, medians of overall survival and progression-free survival of patients with tumors of gastrointestinal tract origin were significantly lower than those of patients with tumors of breast origin (P < 0.0001). Patients with metastatic ovarian tumors of breast origin had significantly better prognosis than those with the tumors from gastrointestinal tract primary malignancies. It is suggested that AEG-1 overexpression might be an independent prognostic marker of metastatic ovarian tumors.

Panax ginseng polysaccharide suppresses metastasis via modulating Twist expression in gastric cancer.

It was previously reported that an antitumor polysaccharide (PGPW1) was isolated from the root of Panax ginseng. To extend our study, we investigated here the anti-invasive and metastatic effects of PGPW1 on human gastric cancer cell line HGC-27 and tried to determine its possible mechanism of action. Both scratch wound-healing and Transwell assay identified that PGPW1 dose-dependently inhibited migration and invasiveness of HGC-27 cells. Furthermore, results of western blot showed that protein levels of Twist and AKR1C2 were inhibited by PGPW1, whereas an increase of NF1 was observed. Moreover, down-regulation of Twist expression by PGPW1 blocked epithelial-mesenchymal transition (EMT), characterized by a gain of epithelial cell markers, E-cadherin, and loss of the mesenchymal markers, vimentin and N-cadherin, at protein levels. Collectively, we confirmed that PGPW1 decreased migration and invasion of HGC-27 cells by regulation of Twist, AKR1C2, NF1, E-cadherin, vimentin and N-cadherin expression. In conclusion, PGPW1 may serve as a powerful chemopreventive agent against gastric cancer metastasis.

Metastasis-induction and apoptosis-protection by TWIST in gastric cancer cells.

TWIST, a basic helix-loop-helix transcription factor, has been recently reported to play an important role in tumorigenesis of human cancer through converting the early stage tumors into invasive malignancies. Upregulation of TWIST is often found in cancer patients, especially those with shorter survival period and poor response to chemotherapy. Here we studied the functions of TWIST on regulating migration rate, apoptosis, and gene expression in gastric cancer cells. TWIST expression is elevated in MGC-803 and HGC-27 cells that exhibit high invasive potential; whereas it is reduced in BGC-823 and SGC-7901 cells that possess relatively low invasive content. To evaluate functional consequences of TWIST induction, we examined the effect of TWIST on cell migration and apoptosis. Overexpression of TWIST in BGC-823 cells resulted in increased migration content and decreased sensitivity to the arsenic oxide-induced cell death. Moreover, small interference RNA-mediated TWIST ablation in MGC-803 and HGC-27 cells showed suppressed migration ability, increased induction of apoptosis in response to arsenic oxide, and elevated cell cycle arrest. Furthermore, we found a negative correlation between the TWIST level and p53 level, probably due to transcriptional regulation. Our results have identified TWIST as a critical regulator of gastric cancer cell proliferation and migration, suggesting a potential therapeutic approach to inhibit the growth and metastasis of gastric cancer through inactivation of TWIST.

Gene expression profiling in TWIST-depleted gastric cancer cells.

TWIST is an important transcription factor during embryonic development and has recently been found to promote the epithelial-mesenchymal transition (EMT) phenomenon seen during the initial steps of tumor metastasis. To further investigate the potential targets and interacting genes of TWIST in human gastric cancer, we performed microarray analysis to compare the gene expression profiles in HGC-27 cells, with or without small interfering RNA (siRNA)-mediated depletion of TWIST. Our results showed that NF1, RAP1A, SRPX, RBL2, PFDN4, ILK, F2R, ERBB3, and MYB were up-regulated, whereas AKR1C2, FOS, GDF15, NR2F1, ATM, and CTPS were down-regulated after TWIST depletion. Moreover, TWIST-depleted HGC-27 cells showed a reversal of the morphologic and molecular changes associated with EMT. These results provide evidence that TWIST regulates the expression of several genes involved in the differentiation, adhesion, and proliferation of gastric cancer cells. The role of TWIST in the development of certain types of gastric cancer is discussed.

[Study on retrograde metastasis rule of middle-low rectal cancer].

OBJECTIVE: To investigate the resection range of mesorectum and rectum below the inferior margin of tumor for the total mesorectum excision (TME) in middle-low rectal cancer. METHODS: Sixty patients were enrolled in the study. After TME operation, serial 5 mm interval sections were made in specimens of middle-low rectal cancer. The retrograde metastasis of rectal cancer was observed by routine HE staining. RESULTS: The phenomena of retrograde metastasis in mesorectum were found in 15 cases, and the distance of retrograde metastasis was 0.5-4.0(2.47+/-1.06) cm, which was correlated with Dukes stage, lymph node metastasis and histological differentiation. The retrograde metastases in bowel were found in 11 cases, and the distance of retrograde metastasis was 0.5-4.0 (1.64+/-1.16) cm, which was correlated with histological differentiation. CONCLUSIONS: The distal mesorectum should be resected at least 4 cm when TME is carried out, and the distal bowel at least 2.5 cm. More than 5 cm mesorectum and bowel should be resected when advanced Dukes stage, extensive lymph node metastasis and poor histological differentiation occurred.