Conservation of receptor antagonist anti-tumor activity by epidermal growth factor receptor antibody expressed in transgenic corn seed

Recombinant protein production in plants such as corn is a promising means to generate high product yields at low comparable production cost. The anti-EGFR monoclonal antibody C225, cetuximab, is a well-characterized receptor antagonist antibody recently approved for the treatment of refractory colorectal cancer. We initiated a study to test and compare the functional activity of glycosylated and aglycosylated C225 produced in stable transgenic corn seed. Both corn antibodies were shown to be functionally indistinguishable from mammalian-derived C225 in demonstrating high-affinity binding to the EGF receptor, blocking of ligand-dependent signaling, and inhibiting cell proliferation. In addition, consistent with cetuximab, both corn antibodies possessed strong anti-tumor activity in vivo. Acute dose primate pharmacokinetic studies, however, revealed a marked increase in clearance for the glycosylated corn antibody, while the aglycosylated antibody possessed in vivo kinetics similar to cetuximab. This experimentation established that corn-derived receptor blocking monoclonal antibodies possess comparable efficacy to mammalian cell culture-derived antibody, and offer a cost effective alternative to large-scale mammalian cell culture production.     

腰椎间盘突出后自然吸收及其相关因素的研究

目的:通过对50例腰椎间盘突出症患者治疗前后的临床资料分析,探讨牵引、手法、针灸等非手术疗法对突出的腰椎间盘自然吸收现象的影响.方法:根据影像学分型将突出后的椎间盘分为突出型、脱出型、游离型,将椎管的形态分为椭圆型、三角型、三叶型.通过椎管横径、矢状径与突出物截面积之比值来观察和分析突出物的变化,所得数据经统计学处理.结果:本研究认为患者椎管的截面积越大自然吸收的机率就越大,椭圆型椎管最好,三角型椎管次之,三叶型椎管最差.根据椎间盘突出的分型,发现纤维环破裂后髓核游离的越远,自然吸收的可能就越大.急性发病,临床症状、体征越重,经本法治疗后临床效果越好,自然吸收的可能就越大,尤其是急性发作的游离型,因突入硬膜囊外的髓核成份多,更易通过排异反应而吸收.结论:牵引和手法等非手术疗法可促进腰椎间盘突出后的自然吸收.     

Recombinant viral protein VP1 suppresses HER-2 expression and migration/metastasis of breast cancer

Breast cancer is one of the most common cancers in women worldwide and metastasis is the major cause of breast cancer death. Development of new therapeutic agents for inhibiting breast cancer metastasis is therefore an urgent need. We previously demonstrated that recombinant DNA-derived viral capsid protein VP1 (rVP1) of foot-and-mouth disease virus-induced apoptosis of MCF-7 breast cancer cells in vitro. Here, we investigated whether rVP1 exhibits any inhibitory effects on migration/metastasis and human epidermal growth factor receptor 2 (HER-2), a well-known biomarker for poor prognosis of breast cancer. The effects of rVP1 on cancer cell migration/invasion and metastasis were evaluated using Transwell migration assay and animal cancer models of metastasis. Western blotting, RT-PCR, flow cytometry, immunohistochemistry, and immunofluorescence staining techniques were used to investigate the effects of rVP1 on HER-2 and signal transduction mediators. Non-cytotoxic concentrations of rVP1-induced mesenchymal-epithelial transition and significantly suppressed AP-2?? and HER-2 expression as well as the migration and invasion of a variety of breast cancer cell lines in a ??1-integrin-dependent manner in vitro. Gross and histopathologic examinations showed that rVP1 also suppressed metastasis of several breast cancer cell lines, including HER-2-overexpressing SK-BR-3 and BT-474 cells to lung, liver, or peripheral lymph node in orthotopic allograft/xenograft murine models. In addition, rVP1 significantly prolonged survival in breast cancer-bearing mice. Notably, no apparent side effects of rVP1 were detected, as shown by normal complete blood count levels and serum biochemistry profiles, including AST, ALT, BUN, and creatine. This study demonstrates that rVP1 suppresses the migration, invasion, and metastasis of breast cancer cells via binding to ??1 integrin receptor and down-regulation of AP-2?? and HER-2 expression. The effectiveness of rVP1 on inhibiting migration/metastasis of breast cancer and HER-2 expression suggests that it may be suitable for serving as potential therapeutics for metastatic breast cancer particularly HER-2-overexpressing cancer.     

Association of mitochondrial deoxyribonucleic acid 16189 variant (T->C transition) with metabolic syndrome in Chinese adults

OBJECTIVE: A common variant in mitochondrial DNA (mtDNA) at bp 16189 (T-->C transition) has been associated with small birth size, adulthood hyperglycemia, and insulin resistance in Caucasians. In this study, we investigated whether mtDNA 16189 variant is associated with metabolic syndrome in Chinese subjects. METHODS: Six hundred fifteen Chinese adults, aged 40 yr or older, were recruited in this study. The 16189 variant of mtDNA was detected using PCR and restriction enzyme digestion. Metabolic syndrome was diagnosed on modified National Cholesterol Education Program Adult Treatment Panel III guidelines, using body mass index (BMI) instead of waist circumference. An association study was performed with chi2 test and logistic regression analysis. RESULTS: The prevalence of the 16189 variant was higher in patients with metabolic syndrome than in those without: 44% (125 of 284) vs. 33.2% (110 of 331) (P = 0.006). The association between this 16189 variant of mtDNA and metabolic syndrome (P = 0.021) remained significant even after correcting for age and BMI. As to the individual traits, the prevalence of fasting plasma glucose of at least 110 mg/dl (> or =6.1 mmol/liter) [(51.5% (121 of 235) vs. 42.1% (160 of 380); P = 0.023], type 2 diabetes mellitus [48.1% (113 of 235) vs. 39.2% (149 of 380); P = 0.031], and hypertriglyceridemia [44.3% (104 of 235) vs. 35.8% (136 of 380); P = 0.037] were significantly higher in subjects harboring the 16189 variant of mtDNA than those with the wild type. However, the prevalence of hypertension [53.2% (125 of 235) vs. 47.6% (181 of 380); P = 0.180], BMI greater than 25 kg/m2 [48.5% (114 of 235) vs. 43.9% (167 of 380); P = 0.270], and low high-density lipoprotein cholesterol [61.3% (144 of 235) vs. 54.7% (208 of 380); P = 0.111] did not reach a significant difference between the two groups. Furthermore, there was a trend of increasing frequency of occurrence of the 16189 variant in individuals having an increasing number of components of metabolic syndrome (Ptrend < 0.005). CONCLUSION: Our data strongly suggest that mtDNA 16189 variant underlies susceptibility to metabolic syndrome in the Chinese population.     

Effects of heterogeneous risk factors on psychological distress in adolescents with autism and victimization experiences in Taiwan

Purpose: To investigate the prevalence of various types of bullying victimization among adolescents with autism spectrum disorder (ASD) and examine the effects of victimization on the mental health of adolescents with ASD.

Methods: The sample was collected from the Special Needs Education Longitudinal Study (SNELS) database released in 2011. Variables comprising seven psychological distress (PD) items and four types of bullying victimization and family-, school-, and peer-related factors were included in a multivariate regression analysis.

Results: Exclusion and verbal bullying were most frequently reported, 72.4% of students with ASD experiencing exclusion bullying and 66% of them experiencing verbal bullying. Among the victims, delayed bedtime, use of medication, and conflicts with parents significantly increased PD. By contrast, good relationships with parents and friends and liking school environments relieved PD symptoms. Furthermore, delayed bedtime after 12 a.m. enhanced the effects of exclusion victimization on PD in the participants.

Conclusions: Our results indicated that bullying victimization among adolescents with ASD was a risk factor for their psychological well-being. Nevertheless, good parent–adolescent and interpeer relationships improved their mental health. Our results can serve as a reference in implementing strategies for motivating parents and teachers to pay more attention to the needs of adolescents with ASD.

• Implications for Rehabilitation

• More than 80% of adolescents with autism experience at least one type of bullying victimization.

• Bullying victimization attributes to a major factor influencing mental health of adolescents with autism.

• Good parent–adolescent and interpeer relationships can play beneficial roles in improving mental health of the adolescents.

     

Prognostic significance of lymph node yield after long‐course preoperative radiotherapy in patients with rectal cancer: a systematic review

Aim A literature review was performed to elucidate whether long‐course preoperative radiotherapy for patients with rectal cancer affects lymph node yield, and whether this influences prognosis. Method Cochrane Database, PubMed/MEDLINE, Scopus, Web of Knowledge, Embase and CINAHL databases and reference lists from published journal articles published between 1 January 1990 and 30 June 2011 were searched. Studies examining lymph node yield and prognosis were selected for review. Results One thousand and twenty‐nine articles were found, of which 11 met the inclusion criteria. None was a randomized controlled trial and all were cohort studies. Four studies showed that long‐course preoperative radiotherapy reduced lymph node yield; however only one demonstrated a statistically significant survival benefit in patients with higher lymph node yields. Five‐year survival was 48% in patients with fewer than and 69% in those with more than 11 lymph nodes identified in the operative specimen (P = 0.04). Conclusion Whilst long‐course preoperative radiotherapy appears to reduce lymph node yield in patients with rectal cancer, no causal relationship between lymph node yield and survival can be established in this group of patients.