High preoperative and postoperative levels of carcinoembryonic antigen and CYFRA 21‑1 indicate poor prognosis in patients with pathological Stage I nonsmall cell lung cancer.

BACKGROUND: Serum carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA 21‑1) are supposed to have a prognostic role in patients with nonsmall cell lung cancer (NSCLC) after surgery, but it has not been used as an adjunct to the tumor‑node‑metastasis (TNM) staging system to provide therapy options for patients with pathological Stage I NSCLC. This study was designed to investigate the effect of serum levels of CEA and CYFRA 21‑1 before and after surgery on the prognosis of patients with Stage I NSCLC. MATERIALS AND METHODS: A retrospective review was performed regarding the medical records and follow‑ups of 169 patients with Stage I NSCLC before and after surgery. The patients were divided into three groups based on levels of serum CEA and CYFRA 21‑1 before and after surgery: (1) continuously normal‑level groups (CEA [NN] and CYFRA 21‑1 [NN] groups); (2) declined to normal‑level groups (CEA [HN] and CYFRA 21‑1 [HN] groups); and (3) continuously high‑level groups (CEA [HH] and CYFRA 21‑1 [HH] groups). Survival analysis was conducted using the Kaplan–Meier method for each group. The Chi‑square or Fisher exact test was employed to compare clinical and pathologic factors at the level of P < 0.05. The prognostic factor was evaluated by the Cox proportional hazards model. RESULTS: Compared with the continuously normal‑level groups, the CEA [HN] group was significantly correlated to tumor size (P = 0.011), and the CYFRA 21‑1 [HN] group was significantly correlated to tumor type and pathological TNM in addition to tumor size. Five‑year survivals were significantly lower (P = 0.004) in the CEA [HH] group (67.3%) and the CEA [HN] group (86.5%) than in the CEA [NN] group (85.7%) and were significantly lower (P < 0.001) in the CYFRA 21‑1 [HH] group (47.2%) and the CYFRA 21‑1 [HN] group (70.1%) than in the CYFRA 21‑1 [NN] group (90.1%). Multivariate analysis demonstrated that tumor size (21–50 mm), CEA [HH], and CYFRA 21‑1 [HH] were independent unfavorable prognostic factors for overall survival (OS), whereas tumor size (21–50 mm), CEA [HH], CYFRA 21‑1 [HN], and CYFRA 21‑1 [HH] were independent significant prognostic factors for progression‑free survival (PFS). CONCLUSION: Patients with a persistently high serum CEA or CYFRA 21‑1 before and after surgery had shortest OS and PFS. These patients had worst prognosis. Adjuvant chemotherapy was likely to improve survival for these patients.

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.

Construction of three different recombinant scorpion fusion proteins with bifunctional activity.

This is the first report of three different fusion proteins with an antitumor-analgesic peptide obtained from Chinese scorpion Buthus martensii Karsch (BmKAGAP). The fusion proteins were constructed in the form of chimeric toxins, aiming to obtain bifunctional analgesic and antitumor activity. The fusion proteins consisted of luteinizing hormone-releasing hormone (LHRH), three different types of flexible linkers (L1, Ser-Ser-His-His-His-His-His-His-Ser-Ser-Gly-Leu-Val-Pro-Arg-Gly-Ser-His-Met; L2, Gly-Gly-Gly-Ser-Gly-Gly-Gly-Ser; L3, Ser-Gly-Gly-Ser-Gly-Gly-Ser-Gly-Gly-Gly-Ser-Ser-Gly-Gly-Ser-Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly-Ser), and BmKAGAP. The genes coding three fusion proteins were cloned and expressed in E. coli in soluble form. Following two successive column chromatographic separations, purified fusion proteins were obtained. These fusion proteins exhibited analgesic activity in mice and were cytotoxic to a hepatocellular carcinoma cell line Hep3B.

Cloning, sequence analysis, and expression of cDNA coding for the major house dust mite allergen, Der f 1, in Escherichia coli

Our objective was to clone, express and characterize adult Dermatophagoides farinae group 1 (Der f 1) allergens to further produce recombinant allergens for future clinical applications in order to eliminate side reactions from crude extracts of mites. Based on GenBank data, we designed primers and amplified the cDNA fragment coding for Der f 1 by nested-PCR. After purification and recovery, the cDNA fragment was cloned into the pMD19-T vector. The fragment was then sequenced, subcloned into the plasmid pET28a(+), expressed in Escherichia coli BL21 and identified by Western blotting. The cDNA coding for Der f 1 was cloned, sequenced and expressed successfully. Sequence analysis showed the presence of an open reading frame containing 966 bp that encodes a protein of 321 amino acids. Interestingly, homology analysis showed that the Der p 1 shared more than 87 percent identity in amino acid sequence with Eur m 1 but only 80 percent with Der f 1. Furthermore, phylogenetic analyses suggested that D. pteronyssinus was evolutionarily closer to Euroglyphus maynei than to D. farinae, even though D. pteronyssinus and D. farinae belong to the same Dermatophagoides genus. A total of three cysteine peptidase active sites were found in the predicted amino acid sequence, including 127-138 (QGGCGSCWAFSG), 267-277 (NYHAVNIVGYG) and 284-303 (YWIVRNSWDTTWGDSGYGYF). Moreover, secondary structure analysis revealed that Der f 1 contained an a helix (33.96 percent), an extended strand (17.13 percent), a ß turn (5.61 percent), and a random coil (43.30 percent). A simple three-dimensional model of this protein was constructed using a Swiss-model server. The cDNA coding for Der f 1 was cloned, sequenced and expressed successfully. Alignment and phylogenetic analysis suggests that D. pteronyssinus is evolutionarily more similar to E. maynei than to D. farinae.

Beneficial effect of recombinant human growth hormone on the intestinal mucosa barrier of septic rats

The objective of the present study was to investigate the effects of recombinant human growth hormone (rhGH) on the intestinal mucosa barrier of septic rats and explore its possible mechanism. Female Sprague-Dawley rats were randomized into three groups: control, Escherichia coli-induced sepsis (S) and treatment (T) groups. Groups S and T were subdivided into subgroups 1d and 3d, respectively. Expression of liver insulin-like growth factor-1 (IGF-1) mRNA, Bcl-2 and Bax protein levels and the intestinal Bax/Bcl-2 ratio, and plasma GH and IGF-1 levels were determined. Histological examination of the intestine was performed and bacterial translocation was determined. rhGH significantly attenuated intestinal mucosal injuries and bacterial translocation in septic rats, markedly decreased Bax protein levels, inhibited the decrease of Bcl-2 protein expression and maintained the Bax/Bcl-2 ratio in the intestine. rhGH given after sepsis significantly improved levels of plasma GH (T1d: 1.28 ± 0.24; T3d: 2.14 ± 0.48 æg/L vs S1d: 0.74 ± 0.12; S3d: 0.60 ± 0.18 æg/L; P < 0.05) and IGF-1 (T1d: 168.94 ± 65.67; T3d: 201.56 ± 64.98 æg/L vs S1d: 116.72 ± 13.96; S3d: 107.50 ± 23.53 æg/L; P < 0.05) and expression of liver IGF-1 mRNA (T1d: 0.98 ± 0.20; T3d: 1.76 ± 0.17 vs S1d: 0.38 ± 0.09; S3d: 0.46 ± 0.10; P < 0.05). These findings indicate that treatment with rhGH had beneficial effects on the maintenance of the integrity of the intestinal mucosa barrier in septic rats.

An effective indirect fluorescent antibody test for diagnosis of intestinal acariasis.

Adult mites' bodies of Dermatophagoides farinae were used as antigen in an indirect fluorescent antibody test (IFAT) to detect mite-specific IgG in sera of 48 patients with intestinal acariasis based on stool examination. Antibody titers with positive reaction ranged from 1:4 to 1:512 in 48 patients with intestinal acariasis. If antibody titers > or = 1:16 is regarded as being positive, the positive rate of patients detected with IFAT was 92%.