Analysis of gene mutation associated with tyrosine kinase inhibitor sensitivity of epidermal growth factor receptor in cervical cancer patients.

OBJECTIVE: Cervical cancer is frequent in females. Epidermal growth factor receptor has a prominent expression in certain malignant tumors. This study aims to observe the expressional profile of epidermal growth factor receptor (EGFR) in cervical cancer patients, and mutation of EGFR gene related with its sensitivity towards tyrosine kinase inhibitor. MATERIALS AND METHODS: Cervical cancer patients from our hospital were recruited as the experimental group, in parallel with chronic cervicitis patients as control group. Serum EGFR level was measured by enzyme-linked immunosorbent assay (ELISA), and EGFR levels in cervical tissues were quantified by immunohistochemistry assay (IHC) staining. Real Time-PCR (RT-PCR) examined mutations of exon 18, 19, and 21 of the EGFR gene, to analyze their correlation with clinical or pathological features. RESULTS: Serum EGFR in experimental group was 1.16 ± 0.04 ng/ml, significantly higher than control group (p < 0.05). EGFR positive rate was 71.1% in cancer tissues, significantly higher compared to controlled or adjacent tissues (p < 0.05). Mutation rats of EGFR exon 19 and exon 21 were 3.3% and 5%, respectively. No mutation was found in exon 18. Such mutations of EGFR gene were related with cancer differentiation grade, tumor-lymph-node-metastasis (TNM) stage, lymph node or distal metastasis (p < 0.05), but not age, Karnofsky performance score (KPS) score or infiltration depth. CONCLUSIONS: EGFR is highly expressed in serum and tumors of cervical cancer patients, some of which showed mutations of exon 19 and 21 of EGFR gene with relatively lower frequency. Mutation rates were significantly higher in patients with highly differentiated grade, early TNM stage, and those without lymph node or distal metastasis.

Orally delivered foot-and-mouth disease virus capsid protomer vaccine displayed on T4 bacteriophage surface: 100% protection from potency challenge in mice.

An orally delivered foot-and-mouth disease (FMD) vaccine has not previously been reported. By using a T4 bacteriophage nanoparticle surface gene-protein display system (T4-S-GPDS), we created a foot-and-mouth disease virus (FMDV) entire capsid protein vaccine candidate. On the T4 phage surface SOC site, a full length FMDV capsid precursor polyprotein (P1, 755 aa) and proteinase 3C (213 aa) derived from an infected pig of serotype O strain GD-10 (1999), were separately displayed on different T4 phage particle surfaces through inserting their coding region DNAs into the T4 phage genome, yielding phage strains T4-P1 and T4-3C. We also constructed a series of FMDV sub-full length capsid structural protein (subunit) containing T4 phage recombinant vaccines. Both sucking and young BALB/c mice were used as two kinds of FMDV vaccine potency evaluation models. Many groups of both model mice were vaccinated orally or by subcutaneous injection with varying FMDV-T4 phage recombinant vaccines, with and without addition of adjuvant, then challenged with a lethal dose of cattle source virulent FMDV. In the case of immunization with a mixture of phage T4-P1 and phage T4-3C particles without any adjuvant added, all mice were 100% protected following either oral or injection immunization, whereas 100% of the control, non-immunized mice and mice immunized with only T4 phage vector Z1/Zh(-) or wild-type T4(+)D phage died; in contrast, with FMDV subunit vaccine, less than 75% protection followed the same potency challenge in both mice model groups. In addition, two pigs immunized with a phage T4-P1 and phage T4-3C mix were protected upon housing together with infected pigs. This study represents a clear example of how FMD and other pathogenic disease vaccines can be prepared by a simple and efficient bacteriophage route.