Serine-arginine protein kinase 1 promotes a cancer stem cell-like phenotype through activation of Wnt/ß-catenin signalling in NSCLC.

Cancer stem cells (CSCs) are commonly associated with cancer recurrence and metastasis that occurs in up to 30-55% of non-small-cell lung carcinoma (NSCLC) patients. Herein, we showed that serine-arginine protein kinase 1 (SRPK1) was highly expressed at both the mRNA and the protein levels in human NCSLC. SRPK1 was associated with the clinical features of human NSCLC, including clinical stage (p < 0.001) and T (p = 0.001), N (p = 0.007), and M (p = 0.001) classifications. Ectopic overexpression of SRPK1 promoted the acquisition of a stem cell-like phenotype in human NSCLC cell lines cultured in vitro. Overexpression of SRPK1 increased sphere formation and the proportion of side-population cells that exclude Hoechst dye. Conversely, SRPK1 silencing reduced the number of spheres and the proportion of side-population cells. Mouse studies indicated that SRPK1 promoted NSCLC cell line tumour growth and SRPK1 overexpression reduced the number of tumour cells required to initiate tumourigenesis in vivo. Mechanistically, gene set enrichment analysis showed that Wnt/ß-catenin signalling correlated with SRPK1 mRNA levels and this signalling pathway was hyperactivated by ectopic SRPK1 expression in NSCLC cell lines. Immunofluorescence demonstrated that SRPK1 enhanced ß-catenin accumulation in the nuclei of NSCLC cell lines, and inhibition of ß-catenin signalling abrogated the SRPK1-induced stem cell-like phenotype. Together, our findings suggest that SRPK1 promotes a stem cell-like phenotype in NSCLC via Wnt/ß-catenin signalling. Moreover, SRPK1 may represent a novel target for human NSCLC diagnosis and therapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Epidemiological investigation of suspected autism in children and implications for healthcare system: a mainstream kindergarten-based population study in Longhua District, Shenzhen.

BACKGROUND: Individuals with autism put a heavy demand on medical services, and prevalence estimates are needed for the planning of such services. Screening for autism in children has important implications for individuals and policy makers. This study aimed to estimate prevalence of suspected autism in children in Longhua District, Shenzhen, and to investigate risk factors for autism. METHODS: A cross-sectional study was conducted in Longhua District, Shenzhen in October 2014. A total of 141 kindergartens were approached and consented to participate in the current study. All children who met the inclusion criteria were screened for autism by using the Autism Behavior Checklist (ABC). RESULTS: 15,200 children in total completed the survey and were included in the final analysis. 2.6 % (95 % CI 2.3-2.9) respondents had a high probability of autism, while 4.0 % (95 % CI 3.7-4.3) respondents had questionable autism. Male children were more likely to develop autism when compared with their female counterparts (P < 0.001). Children of mothers with a lower education level and younger age tended to develop autism (P < 0.001). CONCLUSIONS: Our study shows a high prevalence rate of suspected autism in children which suggests an urgent need of early detection of autism with ABC across the Shenzhen city, or even around China. Further studies with diagnostic procedure are warranted. Maternal age and education level, and gender of children are possible factors related to autism.

Semaphorin 3F induces colorectal cancer cell chemosensitivity by promoting P27 nuclear export.

Colorectal adenocarcinoma (CRC) is the third most common malignancy worldwide. Metastatic CRC has a poor prognosis because of chemotherapy resistance. Our previous study demonstrated that semaphorin 3F (SEMA3F) signaling may contribute to reversing chemotherapy resistance in CRC cells by reducing E-cadherin and integrin αvß3 expression levels. Another study showed that upregulation of p27 significantly increase the expression of E-cadherin and integrin. This study aimed to evaluate the effect of SEMA3F on P27 and whether it can reverse resistance in CRC cells. We compared the chemosensitivity of human colorectal cancer cell lines with different SEMA3F expression levels to 5-Fu through cell experiment and animal experiment. Then the interaction between SEMA3F and p27 and its possible mechanism were explored by Western Blot, immunofluorescence and immunocoprecipitation. We also compared the disease-free survival of 118 CRC patients with high or low expression of SEMA3F.The results showed that overexpresstion of SEMA3F enhanced the chemotherapy sensitivity and apoptosis of CRC cells in vitro and in vivo. Among 118 postoperative CRC specimens, the disease-free survival of patients with positive SEMA3F expression was significantly longer than that with negative SEMA3F expression after adjuvant treatment. Upregulation of SEMA3F in multicellular spheroid culture (MSC) could increase p27 phosphorylation at serine 10 (Ser10), subsequently promote the cytosolic translocation of P27. Overall, our results reveal a novel molecular mechanism: SEMA3F mediates the degradation of p27 and regulates its subcellular localization to enhance chemosensitivity to 5-Fu in CRC cells, rather than inhibits p27 expression.

Efficacy Comparison Between Total Laryngectomy and Nonsurgical Organ-Preservation Modalities in Treatment of Advanced Stage Laryngeal Cancer: A Meta-Analysis.

It remains unclear whether the efficacy of nonsurgical organ-preservation modalities (NOP) in the treatment of advanced-stage laryngeal cancer was noninferiority compared with that of total laryngectomy (TL). The objective of this study was to compare the curative effects between TL and NOP in the treatment of advanced-stage laryngeal cancer through a meta-analysis.Clinical studies were retrieved from the electronic databases of PubMed, Embase, Wanfang, and Chinese National Knowledge infrastructure. A meta-analysis was performed to investigate the differences in the curative efficacy of advanced-stage laryngeal cancer between TL and the nonsurgical method. Two reviewers screened all titles and abstracts, and independently assessed all articles. All identified studies were retrospective.Sixteen retrospective studies involving 8308 patients (4478 in the TL group and 3701 in the nonsurgical group) were included in this meta-analysis. The analysis results displayed the advantage of TL for 2-year and 5-year overall survival (OS)(OR 2.79, 95% CI 1.85-4.23 and OR 1.52, 95% CI 1.09-2.14) as well as in 5-year disease-specific survival (DSS)(OR 1.79, 95% CI 1.61-1.98), but no significant difference in 2-year DSS was detected between the 2 groups (OR = 2.09,95% CI0.69-6.40). Additionally, there were no significant differences between TL and NOP for 5-year local control (LC) either (OR = 1.75, 95% CI 0.87-3.53). When we carried out subgroup analyses, the advantage of TL was especially obvious in T4 subgroups, but not in T3 subgroups.This is the first study to compare the curative effects on advanced-stage laryngeal cancer using meta-analytic methodology. Although there was a trend in favor of TL for OS and DSS, there is no clear difference in oncologic outcome between TL and NOP. Therefore, other factors such as tumor T-stage and size, lymph node metastasis, and physical condition are also important indicators for treatment choice.

Inequalities in Cardiovascular Health Between Local and Migrant Residents: A Cross-Sectional Study of 6934 Participants in Longhua District, Shenzhen.

Household registration status is one social determinant that influences health disparities. This study aimed to investigate the disparities in cardiovascular health between local and migrant residents, which may provide important implications for public health services and may help improve cardiovascular health for residents in Shenzhen.A cross-sectional study was conducted in Shenzhen City Longhua district. Participants were selected for face-to-face interview surveys by using a multistage cluster random sampling design. Chi-square tests and multiple logistic regression models were constructed to compare cardiovascular health between the migrant and local residents.A total of 6934 eligible respondents, of whom 1400 were local and 5534 were migrants, completed the face-to-face interview surveys. The local residents were more likely to have hypertension (3.1% vs. 2.0%, P < 0.05) and diabetes mellitus (1.4% vs. 0.5%, P < 0.05), whilst to be overweight or obese (20.3% vs. 16.4%, P < 0.05) when compared with their migrant counterparts. A higher proportion of local residents than migrant ones had ≥2 cardiovascular risk factors, 2.4% and 1.2%, respectively (P < 0.01). Compared with migrants, the locals were more likely to know their BP values (65.4% vs. 54.5%, P < 0.05) and know the symptoms of diabetes (63.1% vs. 49.7%, P < 0.01).Our study suggests that household registration status is an important driver of social disparities in cardiovascular health except for the factors regarding socioeconomic status. Programs to improve the awareness of hypertension and diabetes are suggested to be initiated among the migrants.

Anti-tumor action of trichosanthin, a type 1 ribosome-inactivating protein, employed in traditional Chinese medicine: a mini review.

Trichosanthin (TCS) as a midterm abortifacient medicine has been used clinically in traditional Chinese medicine for centuries. Additionally, TCS manifests a host of pharmacological properties, for instance, anti-HIV and anti-tumor activities. TCS has been reported to inhibit cell growth of a diversity of cancers, including cervical cancer, choriocarcinoma, and leukemia/lymphoma, etc. This article purported to review the various anti-tumor activities of TCS and the mechanism of apoptosis it induced in these tumor cells. These research progresses provide an insight into cancer research and treatment as well as disclose new pharmacological properties of the ancient but popular Chinese medicine.

[Expressions of 8-OH-dG, k-ras, and p53 genes in pleural effusion cells and their clinical significances].

BACKGROUND & OBJECTIVE: Oxidative DNA damage plays an important role in carcinogens-induced carcinogenesis. 8-hydoxy-2deoxy-guanosine (8-OH-dG), a biomarker of oxidative DNA damage, plays important roles in initiation, progression, and prognosis of lung cancer, and closely relates with mutations of k-ras and p53 genes in carcinogenesis of lung tissue. This study was to detect protein expressions of 8-OH-dG, k-ras, and p53 genes in lung cancer tissues, and to analyze their values in distinguished diagnosis of lung cancer. METHODS: Protein levels of 8-OH-dG, k-ras, and p53 in pleural effusion cells from 53 patients with lung cancer, and 53 patients with other benign lung diseases were detected by immunocytochemistry. RESULTS: Positive rates of 8-OH-dG, k-ras, and p53 protein in cancer group were significantly higher than those in benign disease group [75.5% (40/53) vs. 15.1% (8/53), P < 0.01; 64.2% (34/53) vs. 3.8% (2/53), P < 0.01; and 69.8% (37/53) vs. 18.9% (10/53), P < 0.01; respectively]. Protein levels of 8-OH-dG, k-ras, and p53 protein in cancer group were 1.68+/-1.21, 1.32+/-1.06, and 1.57+/-1.15,respectively. Rank correlation analysis showed that protein expression of 8-OH-dG positively correlated with those of k-ras (RS=0.643, P < 0.01), and p53 (RS=0.827, P < 0.01)u protein expression of k-ras positively correlated with that of p53 (RS=0.897, P < 0.01). CONCLUSIONS: Protein expressions of 8-OH-dG, k-ras, and p53 are up-regulated in pleural effusion cells of lung cancer, and have mutual relations. They may be used as reference markers in diagnosing and screening for lung cancer.