Biomedical subjects

Bin Gu

Publications and source records attributed to Bin Gu.

13 recordsLinked to original sources

PubMed2026

A Biomimetic Dual-Targeting Nano-APA-Editor Reprograms the 3'UTR Landscape for Tongue Squamous Cell Carcinoma Therapy.

Targeting post-transcriptional dysregulation of tumor suppressors represents a new frontier in cancer therapy. Here, we identify the alternative polyadenylation (APA) regulator NUDT21 as a pivotal therapeutic target in oral squamous cell carcinoma (OSCC). NUDT21 is highly upregulated, correlating strongly with poor survival and advanced clinical stage. We outline a pathogenic mechanism whereby NUDT21 drives this phenotype by forcing a network of tumor suppressor transcripts, notably PTEN, into translationally-repressed, long-3'UTR isoforms. To therapeutically "re-engineer" this APA switch, we design a "Nano-APA-editor." This platform features an HMSN core with an sgRNA-NUDT21 payload and a hierarchical targeting strategy: a cancer-educated dendritic cell (DC) membrane for biomimetic camouflage and homotypic affinity, "gated" by a TA-aptamer for final precision. This system enables potent and selective NUDT21 silencing, driving a shift toward short-3'UTR isoforms. Consequently, the Nano-APA-editor effectively reinstates PTEN and associated suppressors and inhibits multiple malignant phenotypes in vitro. In an orthotopic OSCC model, it demonstrates profound tumor regression, outperforming conventional chemotherapy (PTX) with excellent biocompatibility. In vivo analysis confirmed target engagement (NUDT21-down) and functional restoration (PTEN-, WEE1-, TGF-β-up). This work validates a "post-transcriptional re-engineering" strategy, executed by a logically designed nanoplatform, as a powerful and safe modality for precision gene therapy.

Humans↗

PubMed2006

YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients with high-grade gliomas.

PURPOSE: Biomarkers can facilitate diagnosis, monitor treatment response, and assess prognosis in some patients with cancer. YKL-40 and matrix metalloproteinase-9 (MMP-9) are two proteins highly differentially expressed by malignant gliomas. We obtained prospective longitudinal serum samples from patients with gliomas to determine whether YKL-40 or MMP-9 could be used as serum markers. EXPERIMENTAL DESIGN: Serum samples were obtained concurrently with magnetic resonance imaging scans. YKL-40 and MMP-9 were determined by ELISA and the values correlated with the patient's radiographic status and survival. RESULTS: High-grade glioma patients who underwent a surgical resection of their tumor had transient increase of both YKL-40 and MMP-9 serum levels in the postoperative period. Glioblastoma multiforme (GBM) patients with no radiographic evidence of disease (n = 10 patients, 50 samples) had a significantly lower level of YKL-40 and MMP-9 than patients with active tumor (n = 66 patients, 209 samples; P = 0.0003 and 0.0002, respectively). Anaplastic glioma patients with no radiographic evidence of disease (n = 32 patients, 107 samples) also had a significantly lower level of YKL-40 compared with those patients with active tumor (n = 48 patients, 199 samples; P = 0.04). There was a significant inverse association between YKL-40 and survival in GBM, hazard ratio (hazard ratio, 1.4; P = 0.02), and anaplastic astrocytoma patients (hazard ratio, 2.2; P = 0.05). CONCLUSIONS: YKL-40 and MMP-9 can be monitored in patients' serum and help confirm the absence of active disease in GBM and YKL-40 in anaplastic glioma patients. YKL-40 can be used as predictor of survival in patients with high-grade glioma. Longitudinal studies with a larger patient population are needed to confirm these findings.

Adipokines↗

PubMed2006

Nasal reconstruction using a split forehead flap.

BACKGROUND: The pedicle paramedian flap is the most common method used to reconstruct the nose, but secondary operations for debulking are required. In addition, this flap is always limited in length, which makes it hard to form the distal part of the nose. In this study, the authors suggest a split forehead flap with an oblique orientation designed to overcome the disadvantages of the paramedian flap. METHODS: From their practice and review of the literature, the authors discovered that there is a cutaneous branch of the supratrochlear vessels that is set out around the orbital rim, travels subcutaneously, and has a rich anastomotic plexus with other vessels. Therefore, the authors designed a myocutaneous forehead flap with an oblique orientation to lengthen it and split it into two flaps: a muscle flap and a skin flap supplied by the supratrochlear vessels and their cutaneous branch, respectively. In six cases, the muscle flap was used to reconstruct the septum-like structure and wrap the cartilage framework; the skin flap was used to form a new nose. In five cases, the forehead flap was elevated and used as a superthin skin flap to form a new nose with distinct subunits without secondary debulking operations. RESULTS: This improved flap was used in 11 cases with 6 to 25 months of follow-up. In all cases, the authors observed the cutaneous branch of the supratrochlear vessels. All patients were satisfied with their new noses. CONCLUSIONS: This split forehead flap, with an oblique orientation design, has the advantages of achieving good restoration of nasal contour and building septum-like structures and reducing the number of operations.

Adolescent↗

PubMed2006

[Restore hand's function after electric injuries at the wrist by a free composite flap].

OBJECTIVE: To introduce a new free composite flap for the treatment of electric injuries of hands, which can repair the skin, blood vessels, tendons and nerves injuries in just one operation. It may improve the prognosis of electric hand injuries. METHODS: 5 patients with electric injuries at wrist were treated by the free composite flap. The procedure is followed: The composite flap was harvested from medial lateral crural skin flap. Its blood supply was from tibial posterior vessels. The perforans arteries to flap and the branches to plantaris were preserved, and the nerve suralis and tendon plantaris were compound into the flap by carefully dissection of crural fascia. At the same time, 3-4 tendons of extensor digitorum longus were inserted into the superficial crural fascia. Thus, blood vessels, nerves and tendons were combined into the flap before transplantation. The composite flap was then transplanted into the recipient site of the electric injuries of hand to repair the long defects of the skin, blood vessels,nerves and tendons in one operation. The evaluation methods of the prognosis are the follows: the active motion function of finger was assessed by flexion and extension function of the fingers. The sensibility function was tested by the standards recommended by British Medical Association. RESULTS: The patients were followed up from 3 to 12 months. All the flaps were survived. Six months after operation, the flexion distance from tip to palmar crease and extension distance from tip to horizontal level of 3 patients were 4-5 cm and 3-4 cm respectively, and the other 2 patients were recovered from 6 cm and 5 cm to 4 cm and 4 cm respectively. The sensibility of finger skin reached to S2 level, and skin temperature rose. CONCLUSION: The free medial lateral crural composite flap was an ideal one to cure electric injuries at wrist, for it repairs skin, nerves, vessels and tendons defects in just one operation.

Adult↗

PubMed2006

[Establishment of composite facial and scalp allograft transplantation model in canine].

OBJECTIVE: To develop an experimental model of composite facial and scalp allograft in canine in order to investigate technical and immunological aspects and functional recovery of facial muscles of this new approach to facial reconstruction. METHODS: (1) Anatomic study: Four mongrel dogs were used for anatomical dissection of the head and neck region and for harvesting flap experiment. (2) Autologous transplantation (group I): Three types composite facial and scalp autologous transplantation were performed in five mongrel dogs. Type I composite tissue flap (group I a n = 2) included bilateral external ear and orbicularis oculi muscle. Type II (group I b n = 1) included single-lateral external ear, orbicularis oculi muscle, external nose upper and lower lip. Type III (group I c n = 2) included single - lateral external ear and orbicularis oculi muscle. (3) Allograft transplantation (group II): In group II a (n = 2), two allograft transplantation were performed with type III composite facial and scalp . In group II b (n = 4), four allograft transplantation were performed with the modified type III composite facial and scalp which included single - lateral external ear, orbicularis oculi muscle and one third of inferior tarsal plate and palpebral conjunctiva. To prevent allograft rejection, Cyclosporin A (CsA) and Methylprednisolone (MP) or Prednisone (PS ) were combined used as immunosuppressive protocol . Dose of CsA was adjusted depending on its blood drug level. Electromyogram (EMG) of orbicularis oculi muscle was carried out at 4 weeks, 6 weeks, 12 weeks and 6 months postoperation. RESULTS: (1) The facial anatomic characteristic of dog is similar to that of human being, external carotid artery and external jugular vein afford good blood supply to composite facial and scalp. (2) The dogs in group I c were long-term surviving with leakage of salivary juice. (3) In group II a (n = 2), one dog presented rejection reaction at 28th day postoperation, the reversal of rejection was achieved by increasing the dose of CsA and prednisone and with topical clobetasol for 2 weeks, the dog survived indefinitely( > 309 days). In group II b (n = 4), there were three dogs survived indefinitely ( > 159 days, > 129 days, > 108 days) without complication, EMG showed the function of orbicularis oculi muscle was gradually improving. CONCLUSION: The modified type III composite facial and scalp allograft transplantation model is an ideal model for facial allograft transplantation study.

Animals↗

PubMed2005

A "grow-in-place" architecture and methodology for electrochemical synthesis of conducting polymer nanoribbon device arrays.

Fully enclosed horizontal nanochannels, in a prearranged array on a substrate and with built-in electrical contacts and chemical access regions, were used as growth templates for electrochemical synthesis of conducting polymer nanoribbons. In this "grow-in-place" approach, the nanochannel templates are part of the final array structure and remain after fabrication of the nanoribbons. The built-in electrical contacts, which provide the electrical potential for electrochemical polymerization, also remain and become contacts/interconnects to the array components. The grow-in-place architecture and methodology remove the need for template dissolution, any post-synthesis nanoribbon "grow-and-then-place" manipulation, and any post-synthesis electrical contacting. The fact that the templates are fully enclosed prohibits dendrite formation during growth, ensures precise dimensionality, and gives the encapsulation needed in any real device application. In this report the grow-in-place approach to electrochemical polymerization is used to produce polyaniline nanoribbons. These were found to be fibrils and not tubes and to grow from the central region of the growth-template cross-section and not from the template walls. Two-point and four-point electrical characterization of these polyaniline nanoribbons, obtained using the built-in electrodes, was employed to yield the true polyaniline conductivity and to assess the ohmicity of the contacting approach. Conductivity studies, done as a function of nanoribbon width, show conductivity increases as the width decreases. We also show that our grow-in-place approach may be used for chemical polymerization. However, at least for polyaniline, electrochemical polymerization is superior since it does not suffer from diffusion-limited growth and allows precise placement of the nanoribbons in the growth channel.

Aniline Compounds↗

PubMed2005

Enhanced cytotoxicity of bioreductive antitumor agents with dimethyl fumarate in human glioblastoma cells.

We compared the cytotoxicity of the bioreductive antitumor agents mitomycin C (MMC) and streptonigrin (SN) with or without the DT-diaphorase (DTD) inducer dimethyl fumarate (DMF) in four human glioblastoma cell lines with the conventional chemotherapeutic agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). We also examined four other types of cancer cells to compare with glioblastoma cells. Cytotoxicity was measured with the sulforhodamine B (SRB) assay and was represented by 50% inhibition concentration (IC50). Enzymatic activities of DTD, cytochrome b5 reductase and glutathione-S-transferase (GST) in cells were measured spectrophotometrically. IC50 for BCNU was in a range of 28-300 microM in the glioblastoma cell lines. Glioblastoma cells were more sensitive to MMC or SN than to BCNU. Pretreatment with DMF significantly increased cytotoxicity of MMC and SN in glioblastoma cell lines and the NCI-H1299 lung cancer cell line, but had no effect on BCNU cytotoxicity. DMF significantly increased DTD and cytochrome b5 reductase activity, and decreased GST in three of four glioblastoma cell lines. Addition of the DTD inhibitor, dicumarol, significantly inhibited cytotoxicity of MMC and SN, and reversed the increased cytotoxicity seen when DMF was combined with either MMC or SN in all glioblastoma cell lines. Combining inducers of DTD and cytochrome b5 reductase with bioreductive agents may be a potential therapeutic strategy for glioblastoma.

Antineoplastic Agents↗

PubMed2004

Organ-selective chemoresistance in metastasis from human breast cancer cells: inhibition of apoptosis, genetic variability and microenvironment at the metastatic focus.

We hypothesized that the development of the most resistant cells during metastasis is favored by anti-apoptotic proteins, leading to the acquisition of an adaptive phenotype crucial to drug resistance at the metastatic foci. In order to test it, we induced metastasis in nude mice, injecting orthotopicaly 435/Bcl-x(L) or 435/Neo cells, transfected previously with the luciferase gene to use it as a tumor marker, and treated them with a therapeutic dose of docetaxel. We monitored metastasis in mice by calculating tumor cell equivalents (TCEs) present in tissues. Between docetaxel-treated and non-treated 435/Bcl-x(L).luc mice significant differences in the metastatic burden of lymph nodes (P = 0.02) and viscera (P = 0.02) were observed. However, treatment did not significantly decrease metastatic burden in bones (P = 0.19). Additionally, we analyzed the clonality of metastasis from lung, bone and lymph node by genomic DNA fingerprinting. Bcl-x(L) enhanced cell genetic instability in terms of gain and loss fractions (GF = 0.18 and LF = -0.21) when compared with the control 435/Neo (GF = 0.15 and LF = -0.14). Thus, genetic instability might be a molecular mechanism favored by Bcl-x(L) evolved in the selection process of breast cancer progression, which results in different genetic changes among metastases from lung, bone or lymph node, favoring organ-selective chemoresistance.

Animals↗

PubMed2004

Status of methylthioadenosine phosphorylase and its impact on cellular response to L-alanosine and methylmercaptopurine riboside in human soft tissue sarcoma cells.

The aim of this study was to examine the expression of methylthioadenosine phosphorylase (MTAP) in 21 fresh tumor samples from patients with soft tissue sarcomas (STS) and 11 human soft tissue sarcoma cell lines, and to determine if loss of expression of this enzyme was correlated with increased sensitivity to L-alanosine and/or 6-methylmercaptopurine. We used a polyclonal antibody to measure the expression of MTAP in soft tissue sarcoma cell lines and in fresh tumor samples. Transfection of the HT-1080 cell line with a plasmid containing the cDNA for the MTAP gene was also performed to generate cell lines for in vitro and in vivo comparative sensitivity studies. MTAP was not expressed in 8 of 21 fresh STS tumors. The expression of MTAP was also not detectable in 3 of the 11 soft tissue sarcoma cell lines (HT-1080, HS42, and M-9 110). These three cell lines were more sensitive to L-alanosine, a potent inhibitor of de novo AMP synthesis, and to an inhibitor of de novo purine nucleotide synthesis, 6-methylmercaptopurine riboside (MMPR). The IC50 values for L-alanosine and MMPR were >20-fold lower in MTAP-deficient cells than in MTAP-positive cells. Restoration of MTAP into HT-1080 MTAP-deficient cells also led to decreased sensitivity to L-alanosine and MMPR. An in vivo study using HT-1080 cell tumors with and without MTAP expression confirmed that tumors lacking MTAP were more sensitive to L-alanosine than tumors expressing MTAP. These results provide the basis for selective therapy using inhibitors of de novo purine nucleotide synthesis such as L-alanosine or MMPR to treat patients with STS lacking this enzyme.

Alanine↗

PubMed2004

[Nasal reconstruction with forehead skin flap and muscle flap].

OBJECTIVE: To improve the paramedian forehead flap for nasal reconstruction. METHODS: Based on the findings of the Cutaneous branch of supratrochlear artery, the forehead musculo-cutaneous flap was divided into the musculo-flap and the skin-flap in 3 patients. The musculo-flap were used to reconstruct the septi-bone structure, and envelop silicon nasal-frame, while the skin-flap were used to reconstruct the nose. In 6 patients, the forehead flap was used as a skin-flap just with the muscle pedicle to reconstruct a nose with good appearance of nasal subunits, without the secondary operation. RESULTS: In all of 9 cases, the cutaneous-branch of supratrochlear artery was found 1.7-2.0 cm above the orbital-rim. Eight patients got good results, only 1 patient had to do the secondary operation to coverage the exposed nasal frame. CONCLUSIONS: The cutaneous-branch of supratrochlear artery could be an anatomical finding to form the forehead skin-flap and it is a good choice to be used to reconstruct a nose, even in complicated cases.

Adolescent↗

PubMed2003

Formation of nanostructured polymer filaments in nanochannels.

We describe the use of hard etching methods to create nanodimensional channels and their use as templates for the formation of polymer filament arrays with precise dimensional and orientational control in a single integrated step. The procedure is general as illustrated by the radical, coordination, and photochemical polymerizations that were performed in these nanochannels. The nanochannel templates (20 nm high, 20-200 nm wide, and 100 mum long) were fabricated by the combined use of electron-beam lithography and a sacrificial metal line etching technique. Radical polymerization of acrylates, metal-catalyzed polymerization of norbornene, and photochemical polymerization of 1,4-diiodothiophene were carried out in these nanochannels. The polymers grown follow the dimensions and orientation of the channels, and the polymer filaments can be released without breaking. The approach opens up the possibility of just-in-place manufacturing and processing of patterns and devices from nanostructured polymers using well-established polymer chemistry.

Journal Article↗

PubMed2003

[Implementation of mutual information based medical image registration methods].

Image registration methods based on mutual information, including mutual information and normalized mutual information, have been accepted as the most accurate and efficient methods. But there are many fluctuations in the registration functions that hinder the optimization procedure and lead to registration failure in intra-modal registration. We found that besides the interpolation artifacts, the uncertainty of the changing of entropy with the changing of overlap also contributes to the fluctuations. The effect of interpolation artifacts can be eliminated, but it is difficult to eliminate the effect of uncertainty of entropy. Luckily, this effect is not significant in normalized mutual information. Normalized mutual information is more stable and robust than standard mutual information and its better performance and wider application can be expected.

Algorithms↗

PubMed2002

Inhibition of apoptosis in human breast cancer cells: role in tumor progression to the metastatic state.

Reduction in apoptosis has been associated with tumor metastases and response to chemotherapy in breast cancer. We examine the influence of apoptosis status and the expression of antiapoptotic proteins Bcl-2 and Bcl-x(L) on metastatic progression and response to therapy in an experimental model of breast cancer. We used human breast cancer cells (MDA-MB 435, MDA-MB 468 and MCF-7) to induce orthotopic xenograft tumors in nude mice. The overexpression of Bcl-2 or Bcl-x(L) influenced tumorigenicity, 468 transfectants being less tumorigenic than control (p < 0.0001). Lung metastasis appeared at day 120 in animals injected with 435/Bcl-2 or 435/Bcl-x(L) and they showed higher metastatic activity than control 435/Neo tumors (p = 0.02). In contrast, mice with 468 tumors were followed for 1 year after tumor excision, but they did not develop metastatic foci. 435/Bcl-2 and 435/Bcl-x(L) transfectant cells bound less readily to laminin (ANOVA, p < 0.0001), fibronectin (ANOVA, p < 0.0001) and collagen type-IV (ANOVA, p < 0.0001) than 435/Neo cells. The overexpression of antiapoptotic proteins in 435 transfectants rescued 20-40% of cells from anoikis at 64 hr in rocking conditions. In contrast, at this time only 5-10% of 468 and MCF-7 transfectant cells were rescued. Thus, the overexpression of the Bcl-2 or Bcl-x(L) associated with the loss of apoptosis in breast cancer cells in vivo may account for their metastatic behavior. These genes increase tumor metastasis when the oncogenic background has triggered the metastatic process, in which anoikis might determine tumor progression when the life span of the cells is extended.

Animals↗