Integrin-linked kinase is overexpressed in laryngeal squamous cell carcinoma and correlates with tumor proliferation, migration and invasion.

OBJECTIVE: To investigate the role of integrin-linked kinase (ILK) in invasion and metastasis of the laryngeal squamous cell carcinomas (LSCC) and to evaluate the effects of antisense oligonucleotide sequence (ASONs) targeting the ILK gene on the proliferation, epithelial-mesenchymal transition (EMT), migration and invasion of LSCC. PATIENTS AND METHODS: 116 patients who had previously undergone complete resection of the tumor for LSCC were studied retrospectively. The ILK expression level in tumor tissues and adjacent normal tissues were determined by immunohistochemistry. The changes of ILK expression from each group were assessed and correlated to the clinical parameters of the patients. Secondly, ILK antisense oligonucleotide (ILK-ASONS) was used to silence the ILK gene of LSCC cell from Hep-2 cell line. The expression of ILK, epithelial marker E-cadherin and mesenchymal marker Vimentin were evaluated by Western blotting. The proliferation of cells after transfection was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The apoptosis was detected by flow cytometry. The migration and invasion activity of Hep-2 cells was detected by Matrigel invasion and cell migration assays. RESULTS: The expression of the ILK protein was significantly associated with tumor differentiation (p=0.046), lymph node metastasis (p=0.020) and pTNM stage (p=0.019). ILK ASONS-transfected cells showed a significant decrease in cell proliferation, cell migration and invasive activity compared to mock-transfected cells. ILK ASONS-transfected cells increased the expression of E-cadherin, whereas the expression of ILK and Vimentin decreased, compared with mock-transfected cells. CONCLUSIONS: The expression of ILK was significantly correlated with differentiation and metastasis of the laryngeal carcinomas. The inhibition of the ILK gene could downregulate the proliferation, migration and invasion of Hep-2 cells. These findings suggest that the ILK gene could be a potential target for the treatment of laryngeal cancer.

Application of oxaliplatin in combination with epirubicin in transcatheter arterial chemoembolization in the treatment of primary liver carcinoma.

Many cases of liver carcinoma miss the opportunity of surgical treatment because of hidden onset and delayed diagnosis. In recent years, interventional treatment has gradually become a non-surgical method for treating liver carcinoma. To discuss the effects of oxaliplatin in combination with epirubicin in the treatment and its influence on prognosis, this study randomly selected 218 advanced primary liver carcinoma patients from Binzhou People’s Hospital, Binzhou, China and divided them into a control group (n=109) and an observation group (n=109). Patients in both groups were given interventional treatment. Patients in the control group were perfused with oxaliplatin, while patients in the observation group were perfused with oxaliplatin and epirubicin. The effectsat 6-month and 12-month survival rates were compared between the two groups. The results demonstrated that the overall effective rate and clinical benefit rate of the observation group were much higher than those of the control group (30.3% vs 11.9%; 79.8%; vs 44.3%) (P less than 0.05). The serum Alpha Fetal Protein (AFP) and Carcino Embryonie Antigen (CEA) levels of the observation group were much lower than those of the control group; the Karnofsky performance score of the observation group was much lower than that of the control group; the two differences had statistical significance (P less than 0.05). The 6-month survival rate of the observation group was 91.67%, higher than that of the control group (86.11%) (P>0.05). The 12-month survival rate of the observation group was 83.33%, much higher than that of the control group (61.11%) (P less than 0.05). The difference of the incidence of adverse reactions between the two groups had no statistical significance (P>0.05). Thus, it can be concluded that oxaliplatin in combination with epirubicin can improve survival quality, extend survival time, and decrease the serum AFP and CEA levels in the treatment of primary liver carcinoma, with definite effects but without aggravating toxic and side effects. Therefore, the therapy has important clinical value.

[A preliminary study on the outcome of lower-risk myelodysplastic syndrome by low-dose decitabine].

Objective: To assess the efficiency and safety of low-dose decitabine in patients with lower-risk myelodysplastic syndrome (MDS) to couple with the clinical significance of MDS-related gene mutations. Methods: This study was done in 4 institutions in Zhejiang Province. A total of 62 newly diagnosed patients with lower-risk MDS were assigned to two groups of decitabine (12 mg·m(-2)·d(-1) for 5 consecutive days) and best supportive care (BSC) . Their bone marrow samples were subject to examinations of MDS-related 15 gene mutations. The primary endpoints were the proportion of patients who achieved overall response (ORR) after at least two cycles and progression-free survival (PFS) , and their relevances to the gene mutations. Results: Of 62 enrolled patients, and 51 cases were included in the final analysis. 16 of 24 patients (66.7%) in decitabine group achieved ORR versus 8 of 27 (29.6%) in BSC group (χ(2)=6.996, P=0.008) ; PFS prolongation of decitabine versus BSC was statistically significant (not reached vs 13.7 months, P=0.037) . Among 51 patients, at least one gene mutation was identified in 20 patients (39.2%) , including 4 single SF3B1 mutation. PFS in cases with gene mutations (not including single SF3B1 mutation) was significantly shorter than of no gene mutation (9.2 months vs 18.5 months, P=0.008) , but not for ORR (37.5% vs 58.1%, P=0.181) . Among 16 patients with mutated genes, ORR in decitabine and BSC groups were 75% (6/8) and 0 (0/8) , respectively. The most adverse events in decitabine group were grade 3 to 4 neutropenia (45.8%) and grade 3 to 4 infections (33.3%) . Conclusion: This preliminary study showed that low-dose decitabine produced promising results with an acceptable safety in lower-risk MDS patients, especially for those with mutated genes. Further study targeting poor prognostic lower-risk MDS patients should be warranted.

[Expression of enterotoxigenic Bacteroides fragilis and polyketide synthase gene-expressing Escherichia coli in colorectal adenoma patients].

OBJECTIVE: To investigate the distribution of various bacteria in adenoma tissue of colorectal adenoma (T/CRA), normal colonic mucosa tissue adjacent to the adenoma (N/CRA), and healthy colonic mucosa tissue (N/H) by comparing the number of total bacteria, Bacteroides fragilis (BF), enterotoxigenic Bacteroides fragilis (ETBF), polyketide synthase (pks) gene-expressing Escherichia coli(E.coli)(pks(+) E. coli)among the above 3 types of tissues. METHODS: A total of 36 patients diagnosed with colorectal adenoma by colonoscopy and pathology in Department of Gastroenterology, Peking University People's Hospital from September 2011 to September 2013 were selected into this study. T/CRA and N/CRA tissues from the 36 patients and N/H tissues from 18 healthy controls were collected for DNA extraction. The number of total bacteria, BF, ETBF, pks(+) E. coli was detected by quantitative real time PCR, and their correlation with colorectal adenoma was analyzed. RESULTS: (1) The number of total bacteria decreased gradually from N/H, N/CRA, to T/CRA, with the median values being 3.18×10(8,) 1.57×10(8,) and 7.91×10(7) copies/g, respectively, and with significant difference among the three groups and between each two groups (all P<0.01). (2) The content of BF decreased gradually from N/H, N/CRA, to T/CRA, the median values being 6.03×10(5,) 4.28×10(4,) and 5.48×10(3) copies/g, respectively, and with significant difference among the three groups and between each two groups (all P<0.01). (3) The toxin content produced by ETBF increased from N/H, N/CRA, to T/CRA, the relative expression being 1.73±0.30, 6.15±1.52, and 8.54±1.80, respectively. Significant difference was found between the T/CRA and N/H tissue (P=0.003), but not between any other two groups. (4) The expression of clbB in pks(+) E.coli was highest in T/CRA colonic tissue (2.96±0.28), followed by the N/CRA (2.79±0.19) and N/H tissue (1.06±0.08). Significant difference was found between T/CRA and N/H tissues, as well as between N/CRA and N/H tissues (both P<0.001), but not between T/CRA and N/CRA tissues. CONCLUSIONS: The number of total bacteria is markedly reduced in the colonic mucosa of CRA patients compared to normal people, while the expressions of ETBF and pks(+) E.coli are significantly increased. Such changes in total bacterial, ETBF and pks(+) E.coli concentrations in colonic mucosa may be related to the tumorigenesis of colorectal adenoma.

Arterial embolization of massive hepatocellular carcinoma with lipiodol and gelatin sponge.

BACKGROUND: Transarterial chemoembolization (TACE) has been used to treat unresectable massive hepatocellular carcinoma (HCC). Lots of embolic agents have been applied in embolization because of it can decrease patient discomfort and side-effects. AIM: The aim was to evaluate the clinical efficacy and safety of TACE with lipiodol and gelatin sponge. MATERIALS AND METHODS: A total of 109 patients with massive HCC (the size of tumor >10 cm and unresectable) from January 2011 to August 2014 in our institution was divided into group A and group B based on the different embolitic agents. Before and about 1-month after each case of TACE, clinical and biological data such as tumor size, Child-Pugh stage, serum alpha-fetoprotein (AFP), complications, were recorded at the same time. RESULTS: In group A, the diameter of the tumor reduced from 12.57 ± 1.26 cm to 9.04 ± 0.89 cm. No patient was complete response (CR), partial response (PR) 36, stable disease (SD) 7 and PD 6; in group B, the diameter of tumor decreased from 12.08 ± 1.42 cm to 8.43 ± 1.05 cm, CR 0, but PR 27, SD 18 and PD 15. RR in group A was significantly higher than in group B (P < 0.05).The change of Child-Pugh stage and AFP pre- and post-operative in group A can be found significantly better than in group B. CONCLUSIONS: TACE with lipiodol and gelatin sponge is a highly effective for massive HCC.

Transcatheter arterial embolization of acute gastrointestinal tumor hemorrhage with Onyx.

BACKGROUND: Endovascular embolization has been used to control gastrointestinal tumor bleeding. Lots of embolic agents have been applied in embolization, but liquid embolic materials such as Onyx have been rarely used because of concerns about severe ischemic complications. AIM: To evaluate the clinical efficacy and safety of transcatheter arterial embolization (TAE) with Onyx for acute gastrointestinal tumor hemorrhage. MATERIALS AND METHODS: Between September 2011 and July 2013, nine patients were diagnosed as acute gastrointestinal tumor hemorrhage by clinical feature and imaging examination. The angiographic findings were extravasation of contrast media in the five patients. The site of hemorrhage included upper gastrointestinal bleeding in seven cases and lower gastrointestinal bleeding in two cases. TAE was performed using Onyx in all the patients, and the blood pressure and heart rate were monitored, the angiographic and clinical success rate, recurrent bleeding rate, procedure related complications and clinical outcomes were evaluated after therapy. The clinical parameters and embolization data were studied retrospectively. RESULTS: All the patients (100%) who underwent TAE with Onyx achieved complete hemostasis without rebleeding and the patients were discharged after clinical improvement without a second surgery. No one of the patients expired during the hospital course. All the patients were discharged after clinical improvement without a second surgery. Postembolization bowel ischemia or necrosis was not observed in any of the patients who received TAE with Onyx. CONCLUSIONS: TAE with Onyx is a highly effective and safe treatment modality for acute gastrointestinal tumor hemorrhage, even with pre-existing coagulopathy.

OCT4 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b/BAK1 pathway.

Octamer-binding transcription factor 4 (OCT4) is a key regulatory gene that maintains the pluripotency and self-renewal properties of embryonic stem cells. Although there is emerging evidence that it can function as oncogene in several cancers, the role in mediating cervical cancer remains unexplored. Here we found that OCT4 protein expression showed a pattern of gradual increase from normal cervix to cervical carcinoma in situ and then to invasive cervical cancer. Overexpression of OCT4 in two types of cervical cancer cells promotes the carcinogenesis, and inhibits cancer cell apoptosis. OCT4 induces upregulation of miR-125b through directly binding to the promoter of miR-125b-1 confirmed by chromatin immunoprecipitation analysis. MiRNA-125b overexpression suppressed apoptosis and expression of BAK1 protein. In contrast, miR-125b sponge impaired the anti-apoptotic effect of OCT4, along with the upregulated expression of BAK1. Significantly, Luciferase assay showed that the activity of the wild-type BAK1 3'-untranslated region reporter was suppressed and this suppression was diminished when the miR-125b response element was mutated or deleted. In addition, we observed negative correlation between levels of BAK1 and OCT4, and positive between OCT4 and miR-125b in primary cervical cancers. These findings suggest an undescribed regulatory pathway in cervical cancer, by which OCT4 directly induces expression of miR-125b, which inhibits its direct target BAK1, leading to suppression of cervical cancer cell apoptosis.