Juntao Tan

Aptamer-Functionalized Fluorescent Silica Nanoparticles for Highly Sensitive Detection of Leukemia Cells.

A simple, highly sensitive method to detect leukemia cells has been developed based on aptamer-modified fluorescent silica nanoparticles (FSNPs). In this strategy, the amine-labeled Sgc8 aptamer was conjugated to carboxyl-modified FSNPs via amide coupling between amino and carboxyl groups. Sensitivity and specificity of Sgc8-FSNPs were assessed using flow cytometry and fluorescence microscopy. These results showed that Sgc8-FSNPs detected leukemia cells with high sensitivity and specificity. Aptamer-modified FSNPs hold promise for sensitive and specific detection of leukemia cells. Changing the aptamer may allow the FSNPs to detect other types of cancer cells.

An ‘activatable’ aptamer-based fluorescence probe for the detection of HepG2 cells

It is significant to develop a probe with sensitivity and specificity for the detection of cancer cells. The present study aimed to develop an ‘activatable’ aptamer-based fluorescence probe (AAFP) to detect cancer cells and frozen cancer tissue. This AAFP consisted of two fragments: aptamer TLS11a that targets HepG2 cells, and two short extending complementary DNA sequences with a 5′- and 3′-terminus that make the aptamer in hairpin structure a capable quencher to fluorophore. The ability of the AAFP to bind specifically to cancer cells was assessed using flow cytometry, fluorescence spectroscopy and fluorescence microscopy. Its ability to bind to frozen cancer tissue was assessed using fluorescence microscopy. As a result, in the absence of cancer cells, AAFP showed minimal fluorescence, reflecting auto-quenching. In the presence of cancer cells, however, AAFP showed a strong fluorescent signal. Therefore, this AAFP may be a promising tool for sensitive and specific detection of cancer.

Aptamer Combined with Fluorescent Silica Nanoparticles for Detection of Hepatoma Cells

PurposeThe purpose of this study is to develop a simple, effective method to label hepatoma cells with aptamers and then detect them using fluorescent silica nanoparticles (FSNPs).MethodStreptavidin was conjugated to carboxyl-modified fluorescein isothiocyanate (FITC)-doped silica nanoparticles which were prepared by the reverse microemulsion method. The resulting streptavidin-conjugated fluorescent silica nanoparticles (SA-FSNPs) were mixed with hepatoma cells that had been labeled with biotin-conjugated aptamer TLS11a (Bio-TLS11a). The specificity and sensitivity of the nanoprobes were assessed using flow cytometry and fluorescence microscopy. Their toxicity was assessed in normal human liver cell cultures using the MTT assay, as well as in nude mice using immunohistochemistry.ResultsSA-FSNPs showed uniform size and shape, and fluorescence properties of them was similar to the free FITC dye. SA-FSNPs were able to detect aptamer-labeled hepatoma cells with excellent specificity and good sensitivity, and they emitted strong, photobleach-resistant fluorescent signal. SA-FSNPs showed no significant toxic effects in vitro or in vivo.ConclusionThe combination of biotin-conjugated aptamers and SA-FSNPs shows promise for sensitive detection of hepatoma cells, and potentially of other tumor cell types as well.

Association between age and overall survival of patients with hepatocellular carcinoma after hepatic resection.

The suitability of hepatic resection for older patients remains controversial. This study aimed to investigate whether age influences overall survival of patients with hepatocellular carcinoma (HCC) after resection.

Effect of neoadjuvant chemoradiotherapy on perioperative immune function of patients with locally advanced esophageal cancer

This study aims to evaluate the effect of neoadjuvant chemoradiotherapy (NCRT) on perioperative immune function during surgery to treat resectable locally advanced esophageal cancer. Records were retrospectively analyzed for 220 patients with locally advanced esophageal cancer, of whom 112 received surgery alone and 98 received neoadjuvant NCRT plus surgery. The two groups were compared in terms of proportions of CD3+, CD4+, CD8+, and natural kill (NK) cells, as well as the ratio of CD4+ to CD8+ cells. These measurements were made using flow cytometry on preoperative day 1 and on postoperative days 1 and 7. Subgroup analysis were performed in terms of degrees of pathological response of NCRT. When the entire NCRT and no-NCRT (surgery alone) cohorts were compared, no significant differences in propocrtions of CD3+, CD4+, CD8+, or NK cells or in the CD4+/CD8+ ratio occurred at any of the three time points. Similar results were obtained using the subgroup of NCRT patients who were NCRT-sensitive, but the subgroup of NCRT-insensitive patients showed significantly lower CD4+ and NK proportions and lower CD4+/CD8+ ratio than the no-NCRT group. Our findings suggest that NCRT does not affect perioperative immune function in patients who are NCRT-sensitive, but it does significantly reduce such function in patients who are NCRT-insensitive.

Association between COX-2 gene polymorphisms and risk of hepatocellular carcinoma development: a meta-analysis

Objective To investigate the association between cyclo-oxygenase-2 (COX-2) polymorphism and the risk of hepatocellular carcinoma (HCC) development. Design Systematic review and meta-analysis of COX-2 polymorphism and risk of HCC development among people with or without HCC. Data sources EMBASE, PubMed, Public Library of Science, SCOPUS, Web of Knowledge and Chinese National Knowledge Infrastructure were searched for all clinical and experimental case–control studies of COX-2 polymorphism and HCC risk. Studies published up to March 2015 were included. Review method Ten studies were included for data extraction, which were mainly from Asian countries. Results 2538 people with HCC and 3714 without HCC were found to satisfy the inclusion criteria and included in the review. The associations of specific genotypes in the eight polymorphic variants of COX-2 and the risk of HCC development were analysed. GG genotype at the A-1195G polymorphism may be associated with a reduced risk of HCC development: the OR across all studies was 0.87 (95% CI 0.75 to 1.02) for the G allele versus the A allele, 0.72 (0.53 to 0.97) for GG versus AA, 0.72 (0.57 to 0.92) for GG versus GA+AA and 1.05 (0.77 to 1.44) for AA versus GA+GG. Similar results were found when the meta-analysis was repeated separately for the Chinese subgroup. However, more reliable data are needed to demonstrate associations between variants in G-765C, T+8473C, A-1290G, G-899C and introns 1, 5 and 6 polymorphisms and the risk of HCC development. Conclusions Only the COX-2 A-1195G gene polymorphism may be associated with a decreased risk of HCC development. These conclusions should be verified in further studies.

Graphene-Based Multifunctional Nanomaterials in Cancer Detection and Therapeutics

Nanotechnology for early diagnosis and treatment of malignant tumor is a forefront topic in the international field of biotechnology and medicine. In order to improve the effect of cancer therapy, the timely and accurate detection of the cancer is important and necessary. Graphene and its derivatives have various excellent characteristics. For example, biological sensors based on graphene are good at amplifying detection signals, and its derivatives play an important role in the early diagnosis and cancer therapy. In view of this, we discussed the biological sensor application based on graphene and its derivatives in the detection and therapy of cancer.

Screening and antitumor effect of an anti‑CTLA‑4 nanobody

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a critical negative regulator of immune responses. CTLA-4 is rapidly upregulated following T-cell activation, and then binds to B7 molecules with a higher affinity than CD28. CTLA-4 may abolish the initiation of the responses of T cells by raising the threshold of signals required for full activation of T cells, and it also may terminate ongoing T-cell responses. This regulatory role has led to the development of monoclonal antibodies (mAbs) designed to block CTLA-4 activity for enhancing immune responses against cancer. mAbs have several disadvantages including high production cost and unstable behavior. Nanobodies (Nbs) are single-domain antigen-binding fragments derived from the camelid heavy-chain antibodies, which are highly attractive in cancer immunotherapy due to their small size, high specificity, and stability. We selected CTLA-4-specific Nbs from a high quality dromedary camel immune library by phage display technology. Four positive colonies were sequenced and classified based on the amino acids sequences in the CDR3 region. These Nbs recognized unique epitopes on CTLA-4 and displayed high binding rates when used on PHA-stimulated human T cells. Treatment of B16 melanoma-bearing C57BL/6 mice with anti-CTLA-4 nanobody 16 (Nb16) delayed melanoma growth and prolonged the survival time of mice. These data indicate that anti-CTLA-4 Nbs selected from a high quality phage display library may be effective for the treatment of patients with tumors.