The safety and effectiveness of a self-made negative pressure suction device in the treatment of chronic wounds.

INTRODUCTION: Chronic wounds are wounds that are not healed or have no healing tendency for more than 1 month due to various factors. In clinical nursing, chronic wounds are often not properly treated, and the treatment efficiency is low. Therefore, it is very important to explore effective methods to deal with chronic wounds. OBJECTIVE: To explore the effect of a self-made negative pressure suction device (NPSD) in the nursing of chronic wounds in the elderly. METHODS: A total of 50 elderly patients with chronic wounds who were hospitalised in our hospital from January 2020 to December 2022 were selected as participants by convenient sampling. According to the random number table method, they were divided into a control group and an observation group, with 25 people in each group. The control group was treated with chloroplast foam dressing, debridement gel and alginate dressing. The observation group was treated with a self-made NPSD on the basis of the control group. The wound healing of the two groups was observed. RESULTS: After the intervention of the self-made NPSD, the granulation tissue coverage rate and wound volume reduction rate of the observation group were significantly increased (p < 0.05), and the positive rate of bacterial infection was significantly decreased (p < 0.05). After 3 months of intervention, the total effective rate of the observation group was significantly higher than that of the control group (χ2  = 3.869, p = 0.0492). CONCLUSION: The self-made NPSD can effectively promote the healing of a chronic wound.

Clinical Significance of Pim-1 in Human Cancers: A Meta-analysis of Association with Prognosis and Clinicopathological Characteristics.

BACKGROUND: Pim-1 is overexpressed in cancer tissues and plays a vital role in carcinogenesis. However, its clinical significance in cancers is not fully verified by meta-analysis, especially in relation to prognosis and clinicopathological features. METHODS: Four databases, PubMed, Embase, Cochrane Library, and Web of Science, were searched. Literature screening and data extraction according to the inclusion and exclusion criteria. The quality of the included literatures was evaluated using the Newcastle-Ottawa scale and the data analysis was performed using STATA and Review Manager software. RESULTS: 15 articles were finally included for meta-analysis, involving 1651 patients. Effect-size pooling analysis showed that high Pim-1 was related to poor overall survival (OS) (HR 1.68 [95% CI 1.17-2.40], P = .004) and disease-free survival (DFS) (HR 2.15 [95 %CI 1.15-4.01], P = .000). Subgroup analysis indicated that the detection techniques of Pim-1 were the main sources of heterogeneity, and 2 literatures using quantitative polymerase chain reaction (qPCR) for Pim-1mRNA had high homogeneity (I2 = .0%, P = .321) in OS. Another 13 studies that applied immunohistochemistry (IHC) for Pim-1 protein had significant heterogeneity (I2=82.2%, P = .000; I2=92%, P = .000) in OS and DFS, respectively, and further analysis demonstrated that ethnicity, sample size, and histopathological origin were considered to be the main factors affecting their heterogeneity. In addition, high Pim-1 was associated with lymph node metastasis (OR 1.40 [95% CI 1.02-1.92], P = .04), distant metastasis (OR 2.69 [95%CI 1.67-4.35], P < .0001), and clinical stage III-IV (OR .7 [95% CI .50-.96, P = .03). Sensitivity analysis suggested that the pooled results of each effect-size were stable and reliable, and there was no significant publication bias (P = .138) in all included articles. CONCLUSION: High Pim-1 can not only predict poor OS and DFS of cancer, but also help to infer the malignant clinical characteristics of tumor metastasis. Pim-1 may be a potential and promising biomarker for early diagnosis, prognostic analysis and targeted therapy of tumors.

Association of Epstein-Barr virus DNA and SAA with S1 maintenance therapy outcomes in patients with metastatic nasopharyngeal carcinoma.

Objectives: The relevant biomarkers in predicting maintenance therapy (MT) outcomes in metastatic nasopharyngeal carcinoma (NPC) are yet unclear. Patients & methods: Metastatic NPC patients were randomly divided into MT (S1-MT) and non-MT groups. The association of Epstein-Barr virus DNA (EBV-DNA) and SAA with survival was assessed. Results: A total of 183 patients were included. S1-MT significantly increased the progression-free survival (PFS) and overall survival (OS) of the metastatic NPC patients (both p < 0.001). For patients who were EBV-DNA positive or had decreased SAA, the PFS and OS increased significantly after S1-MT (both p < 0.001), while patients with stable SAA did not benefit from S1-MT. Conclusion: S1-MT improved the PFS and OS of metastatic NPC patients. EBV-DNA and SAA status were closely associated with the outcomes of S1-MT. Clinical trial registration number: ChiCTR-IOR-16007939.

A positive feedback loop between Wnt/ß-catenin signaling and hTERT regulates the cancer stem cell-like traits in radioresistant nasopharyngeal carcinoma cells.

Radioresistance may be induced by cancer stem cells (CSCs), while the biological traits of CSCs need to be retained by telomerase. The telomerase activity mainly depends on the transcriptional regulation of human telomerase reverse transcriptase (hTERT). Moreover, Wnt/ß-catenin signaling is also considered essential for maintaining the CSC phenotypes. In the previous study, we discovered that the radioresistant nasopharyngeal carcinoma cells CNE-2R displayed CSC-like traits, as well as high expression of hTERT and ß-catenin, but whether hTERT and ß-catenin were involved in regulating the CSC-like traits and radiosensitivity of CNE-2R cells remained unclear. In this study, our results suggested that hTERT could positively regulate the expression of CSC-related proteins, as well as the cytoplasm- and nucleus-ß-catenin, but it could not markedly regulate the expression of total ß-catenin in CNE-2R cells. Meanwhile, Wnt/ß-catenin signaling had a positive regulatory effect on the expression of hTERT and CSC-related proteins. Moreover, there was a ß-catenin/hTERT protein complex in CNE-2R cells, indicating that ß-catenin could directly interact with hTERT protein. Our results also revealed that silencing hTERT or suppressing Wnt/ß-catenin signaling could attenuate telomerase activity and radioresistance of CNE-2R cells; while suppressing Wnt/ß-catenin signaling, the telomerase activity and radioresistance could be reversed through overexpressing hTERT. Taken together, we have outlined a positive feedback loop between Wnt/ß-catenin signaling and hTERT in CNE-2R cells, which can regulate the telomerase activity and CSC-like traits, thus regulating the radiosensitivity. Therefore, blocking Wnt/ß-catenin signaling transduction and interfering with hTERT expression may be a promising approach for targeting radioresistant nasopharyngeal carcinoma cells with CSC-like traits.

Platinum single-agent vs. platinum-based doublet agent concurrent chemoradiotherapy for locally advanced cervical cancer: A meta-analysis of randomized controlled trials.

OBJECTIVES: This study compared treatment outcomes and adverse events in patients with locally advanced cervical cancer undergoing radiotherapy (RT) with concurrent platinum-based doublet therapy vs. RT plus platinum single-agent therapy. The main outcomes were progression-free survival (PFS), overall survival (OS), and the occurrence of adverse events. METHODS: We comprehensively searched Medline, Embase, the Cochrane Library, China National Knowledge Web, Wanfang Database, and VIP database, and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) by using the fixed-effect or random-effect models. The primary endpoints were OS and PFS, reported as hazard ratios (HRs) and 95% confidence intervals (95% CIs). The meta-analysis was performed with RevMan 5.2. RESULTS: Seven randomized trials including 1503 patients were identified. The meta-analysis showed that, for locally advanced cervical cancer, concurrent RT with platinum-based doublet chemotherapy significantly improved the OS (HR 0.75, 95% CI 0.60-0.94, p = 0.01) and the PFS (HR 0.78, 95% CI 0.65-0.94，p = 0.01) compared to RT with cisplatin monotherapy. Grade 3 or 4 vomiting (related ratio [RR] = 3.19, 95% CI 1.85-5.49, p < 0.0001) and thrombocytopenia (RR = 2.75, 95% CI 1.39-5.44, p = 0.004) occurred more frequently in the polychemotherapy arm. The incidence of urinary system toxicity tended to be higher in the polychemotherapy arm (RR = 4.58, 95% CI 1.00-20.89, p = 0.05). CONCLUSIONS: Under the premise of good tolerance, RT plus platinum-based doublet therapy improves survival compared to RT plus platinum single-agent therapy in patients with locally advanced cervical cancer.

SH3BP1-induced Rac-Wave2 pathway activation regulates cervical cancer cell migration, invasion, and chemoresistance to cisplatin.

Cervical cancer still remains the fourth most common cancer, affecting women worldwide with large geographic variations in cervical cancer incidence and mortality rates. SH3-domain binding protein-1 (SH3BP1) specifically inactivating Rac1 and its target Wave2 is required for cell motility, thus regarded as an essential regulator of cancer cell metastasis. However, the exact effects and molecular mechanisms of SH3BP1 in cervical cancer progression are still unknown. The present study is aimed to investigate the mechanism of SH3BP1 in regulation of cervical cancer cell metastasis and chemoresistance. In the present study, we demonstrated a high SH3BP1 expression in cervical cancer tissues; a higher SH3BP1 expression is also correlated with a shorter overall survival of patients with cervical cancer. Further, we revealed that SH3BP1 overexpression promoted the invasion, migration, and chemoresistance of cervical cancer cell through increasing Rac1 activity and Wave2 protein level. The promotive effect of SH3BP1 could be partially reversed by a Rac1 inhibitor, NSC 23766. In cisplatin-resistant cervical cancer tissues, SH3BP1, Rac1, and Wave2 mRNA expression was significantly up-regulated compared to that of the cisplatin-sensitive cervical cancer tissues. Taken together, SH3BP1/Rac1/Wave2 pathway may potentially act as an effective therapeutic target combined with traditional cisplatin-based chemotherapy for cervical cancer.

Glioma-Targeted Drug Delivery Enabled by a Multifunctional Peptide.

The rapid proliferation of glioma relies on vigorous angiogenesis for the supply of essential nutrients; thus, a radical method of antiglioma therapy should include blocking tumor neovasculature formation. A phage display selected heptapeptide, the glioma-initiating cell peptide GICP, was previously reported as a ligand of VAV3 protein (a Rho GTPase guanine nucleotide exchange factor), which is overexpressed on glioma cells and tumor neovasculature. Therefore, GICP holds potential for the multifunctional targeting of glioma (tumor cells and neovasculature). We developed GICP-modified micelle-based paclitaxel delivery systems for antiglioma therapy in vitro and in vivo. GICP and GICP-modified PEG-PLA micelles (GICP-PEG-PLA) could be significantly taken up by U87MG cells, a human cell line derived from malignant gliomas and human umbilical vein endothelial cells (HUVECs). Furthermore, GICP-PEG-PLA micelles demonstrated enhanced penetration in a tumor spheroid model in vitro in comparison to unmodified micelles. In vivo, DiR-loaded GICP-PEG-PLA micelles exhibited superior accumulation in the tumor region by targeting neovasculature and glioma cells in nude mice bearing subcutaneous glioma. When loaded with paclitaxel, GICP-PEG-PLA micelles could more effectively suppress tumor growth and neovasculature formation than unmodified micelles in vivo. Our results indicated that GICP could serve as a promising multifunctional ligand for glioma targeting.

Noninvasive delivery of oligonucleotide by penetratin-modified polyplexes to inhibit protein expression of intraocular tumor.

Our present study aimed to develop an antisense oligonucleotide (ASO) delivery system to achieve gene silencing in intraocular tumor via topical instillation. ASO specific for luciferase was chosen as model drug, polyamidoamine (PG5) was employed to condense ASO, and penetratin (Pene) was used to enhance cellular uptake. Nanoscale PG5/ASO/Pene polyplex was stabilized via noncovalent bonding. In vitro evaluations indicated that PG5/ASO/Pene exhibited improved cell-penetrating and gene silencing ability compared with naked ASO and PG5/ASO. Subcutaneous and orthotopic tumor models expressing luciferase were established in nude mice. After treated by PG5/ASO/Pene, immunohistochemical results of subcutaneous tumors showed significant inhibition of luciferase expression via peritumoral injection, and bioluminescence from orthotopic tumor was obviously weakened via topical instillation. To date, few works were successful in noninvasive treatment of intraocular diseases using antisense strategy, this penetratin-modified polyplex could be a promising vector to inhibit protein expression by effectively delivering ASOs into the eye.

Functional Interrogation of the N-Terminal Lid of MDMX in p53 Binding via Native Chemical Ligation.

The homologous proteins MDM2 and MDMX negatively regulate the tumor suppressor protein p53 by antagonizing p53 transactivation activity and targeting p53 for degradation. MDM2 and MDMX bind to p53 via N-terminal p53-binding domains to control the level of p53. The N-terminal regions of MDM2 and MDMX are modified in vivo under stressed conditions, suggesting that modifications to MDM2/MDMX also may affect the p53-MDM2/MDMX interaction. Ample evidence suggests that the MDM2 lid (residues 1-24) is partially structured and significantly reduces its binding affinity with p53 several fold. Since MDM2 and MDMX possess very similar p53-binding domains but different lids, however, the function of the N-terminal lid of MDMX still remains poorly understood. Using a native chemical ligation technique, the p53-binding domain of MDMX, (1-108)MDMX, and its N-terminal lid (residues 1-23) truncated analogue (24-108)MDMX were chemically synthesized. We comparatively characterized their structures by circular dichroism (CD) spectra, and measured their binding affinities with a panel of p53-derived peptide ligands by fluorescence polarization and surface plasmon resonance assays. Our results indicate that, as opposed to the lid of MDM2, the lid of MDMX has little effect on p53-binding, adopts no structural conformation, and has rare auto-inhibitory function. Different lid modifications of MDM2 and MDMX are functionally different with respect to p53 binding, which should be considered when designing dual specific inhibitors of MDM2 and MDMX.

Total chemical synthesis of human interferon alpha-2b via native chemical ligation.

Interferon-alpha (IFNα) is a cytokine that orchestrates innate and adaptive immune responses and potently inhibits proliferation of normal and tumor cells. These properties have warranted the use of IFNα in clinical practice for the treatment of several viral infections and malignancies. However, overexpression of IFNα leads to immunopathology observed in the context of chronic viral infections and autoimmune conditions. Thus, it is desirable to develop therapeutic approaches that aim at suppressing excessive IFNα production. To that end, artificial evolution of peptides from phage display libraries represents a strategy that seeks to disrupt the interaction between IFNα and its cell surface receptor and thus inhibit the ensuing biological effects. Mirror-image phage display that screens peptide libraries against the D-enantiomer is particularly attractive because it allows for identification of proteolysis-resistant D-peptide inhibitors. This approach, however, relies on the availability of chemically synthesized D-IFNα composed entirely of D-amino acids. Here, we describe the synthesis and biological properties of IFNα2b of 165 amino acid residues produced by native chemical ligation, which represents an important first step toward the discovery of D-peptide antagonists with potential therapeutic applications.

Retro-inverso isomer of Angiopep-2: a stable d-peptide ligand inspires brain-targeted drug delivery.

The blood-brain barrier (BBB) prevents most drugs from reaching the site of central nervous system (CNS) diseases, intensively confining the therapeutic efficiency. Angiopep-2 (here termed (L)Angiopep), which is a 19-mer peptide derived from human Kunitz domain, can trigger transcytosis and traverse the BBB by recognizing low density lipoprotein-related protein 1 (LRP-1) expressed on the brain capillary endothelial cells. Various enzymes in the blood and the BBB, however, present multiple metabolic barriers to peptide-inspired brain-targeted drug delivery. Here we designed a retro-inverso isomer of (L)Angiopep, termed (D)Angiopep, to inspire brain-targeted drug delivery. Both (D)Angiopep and (L)Angiopep displayed high uptake capacity in LRP-1 overexpressed cells, including bEnd.3 and U87 cells. (D)Angiopep demonstrated lower uptake efficiency in both cell lines than did (L)Angiopep, suggestive of lower binding affinity to LRP-1 of the d-peptide. (D)Angiopep was resistant to proteolysis in fresh rat blood serum, while more than 85% of (L)Angiopep disappeared within 2 h. Endocytosed (D)Angiopep and (L)Angiopep were found to be colocalized with lysosomal compartments of bEnd.3 cells, indicating that susceptibility to proteolysis of (L)Angiopep in the BBB may further attenuate its transcytosis efficiency. In vivo, (D)Angiopep modified PEG-DSPE micelles displayed high distribution in normal brain and intracranial glioblastoma. Due to the expression of LRP-1 on the BBB and glioblastoma cells, proteolytically stable (D)Angiopep holds much potential for designing two-order brain tumor targeted delivery systems.

Total chemical synthesis of dengue 2 virus capsid protein via native chemical ligation: role of the conserved salt-bridge.

The dengue capsid protein C is a highly basic alpha-helical protein of ~100 amino acid residues that forms an emphipathic homodimer to encapsidate the viral genome and to interact with viral membranes. The solution structure of dengue 2 capsid protein C (DEN2C) has been determined by NMR spectroscopy, revealing a large dimer interface formed almost exclusively by hydrophobic residues. The only acidic residue (Glu87) conserved in the capsid proteins of all four serotypes of dengue virus forms a salt bridge with the side chains of Lys45 and Arg55'. To understand the structural and functional significance of this conserved salt bridge, we chemically synthesized an N-terminally truncated form of DEN2C ((WT)DEN2C) and its salt bridge-void analog (E87A)DEN2C using the native chemical ligation technique developed by Kent and colleagues. Comparative biochemical and biophysical studies of these two synthetic proteins using circular dichroism spectroscopy, fluorescence polarization, protein thermal denaturation, and proteolytic susceptibility assay demonstrated that the conserved salt bridge contributed to DEN2C dimerization and stability as well as its resistance to proteolytic degradation. Our work provided insight into the role of a fully conserved structural element of the dengue capsid protein C and paved the way for additional functional studies of this important viral protein.

Functional consequences of retro-inverso isomerization of a miniature protein inhibitor of the p53-MDM2 interaction.

Peptide retro-inverso isomerization is thought to be functionally neutral and has been widely used as a tool for designing proteolytically stable d-isomers to recapitulate biological activities of their parent l-peptides. Despite success in a wide range of applications, exceptions amply exist that clearly defy this rule of thumb when parent l-peptides adopt an α-helical conformation in their bound state. The detrimental energetic effect of retro-inverso isomerization of an α-helical l-peptide on its target protein binding has been estimated to be 3.0-3.4kcal/mol. To better understand how the retro-inverso isomer of a structured protein works at the molecular level, we chemically synthesized and functionally characterized the retro-inverso isomer of a rationally designed miniature protein termed stingin of 18 amino acid residues, which adopts an N-terminal loop and a C-terminal α-helix stabilized by two intra-molecular disulfide bridges. Stingin emulated the transactivation peptide of the p53 tumor suppressor protein and bound with high affinity and via its C-terminal α-helix to MDM2 and MDMX-the two negative regulators of p53. We also prepared the retro isomer and d-enantiomer of stingin for comparative functional studies using fluorescence polarization and surface plasmon resonance techniques. We found that retro-inverso isomerization of l-stingin weakened its MDM2 binding by 720 fold (3.9kcal/mol); while enantiomerization of l-stingin drastically reduced its binding to MDM2 by three orders of magnitude, sequence reversal completely abolished it. Our findings demonstrate the limitation of peptide retro-inverso isomerization in molecular mimicry and reinforce the notion that the strategy works poorly with biologically active α-helical peptides due to inherent differences at the secondary and tertiary structural levels between an l-peptide and its retro-inverso isomer despite their similar side chain topologies at the primary structural level.(1.)

Maintenance therapy improves the survival outcomes of patients with metastatic nasopharyngeal carcinoma responding to first-line chemotherapy: a multicentre, randomized controlled clinical study.

PURPOSE: To explore the safety and role of tegafur/gimeracil/oteracil (S1) maintenance therapy (MT) in metastatic nasopharyngeal carcinoma (NPC) patients after response to first-line chemotherapy and to assess outcome-associated biomarkers. METHODS: This was a multicentre, open-label, randomized controlled study involving metastatic NPC patients recruited (from May 2015 to May 2019) at five hospitals in China. The participants were randomized to S1-MT (receiving S1 MT until disease progression or intolerance) or non-MT (followed up until disease progression) groups. The primary endpoint was the progression-free survival (PFS). The secondary endpoints were the overall survival (OS), the correlation between EBV-DNA, serum amyloid A (SAA) status, and outcomes after the first-line chemotherapy, and safety. RESULTS: The median follow-up was 24.3 months; 88 and 95 participants were evaluable in the S1-MT and non-MT groups, respectively. Compared with non-MT, S1-MT prolonged PFS (16.9 vs. 9.3 months, P < 0.001) and OS (33.6 vs. 20.6 months, P < 0.001). Regardless of their EBV-DNA status after first-line chemotherapy, participants were able to benefit from S1 MT, but EBV-DNA-positive participants benefited more significantly (PFS: HR = 0.600, 95% CI = 0.373-0.965, P = 0.035; OS: HR = 0.393, 95% CI = 0.227-0.681, P = 0.001). MT only improved PFS and OS in patients with an SAA decline after first-line chemotherapy (PFS: HR = 0.570, 95% CI = 0.350-0.919, P = 0.021; OS: HR = 0.404, 95% CI = 0.230-0.709, P = 0.002). The median S1 treatment was 23 cycles. Grade 1-2 skin pigmentation, oral mucositis, and hand and foot syndrome were the main adverse reactions. CONCLUSION: For metastatic NPC patients with first-line chemotherapy response, S1 MT can improve PFS and OS, with good tolerability. EBV-DNA and SAA can better help us identify patients who can benefit from MT after standard treatment. TRIAL REGISTRATION: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR-IOR-16007939).

A cyanine based fluorophore emitting both single photon near-infrared fluorescence and two-photon deep red fluorescence in aqueous solution.

Optical imaging provides an indispensable way to locate tumors in their early stages with high sensitivity and signal to background ratio. A heptamethine cyanine based fluorophore that emits both single photon near-infrared fluorescence and two-photon deep red fluorescence under physiological conditions was developed. Linear and nonlinear photophysical properties of this fluorophore were investigated and it demonstrated the capability to label lysosomes in cancer cells. The advantages of this fluorophore, including tolerable cytotoxicity, high fluorescence quantum yield, and the ability to emit both near-infrared single photon fluorescence and deep red two photon fluorescence in aqueous solution, give it potential to be used in intra-operatively optical image-guided tumor excision followed by two-photon fluorescence microscopy biopsy analysis after a single administration.

[Effect of fluoride on expression of CaN mRNA and protein in bone tissue of rats].

OBJECTIVE: To investigate the changes of mRNA and protein expression of CaN in the bone of rats with chronic fluorosis, and the mechanism of skeletal fluorosis. METHODS: Thirty-six SD rats were divided into three groups (12 in each group, half male and half female selected according to body weight): control, low-dose and high-dose fluorosis groups. Controls were fed tap water (NaF < 0.5 mg/L), experimental animals in the low- or high-dose groups were fed water containing NaF of 5.0 and 50.0 mg/L, respectively. The rats were sacrificed after 6 months of treatment with fluoride. The serum was kept for testing bone metabolic marker bone gla protein (BGP) by enzyme-linked immunosorbent assay (ELISA), the protein and mRNA levels of CaN in distal femur of the rats with chronic flurosis were assessed by immunohistochemistry and in-situ hybridization. RESULTS: The levels of BGP (1.99 ± 0.62, 2.38 ± 0.16)µg/L in the low- or high-dose fluorosis groups were higher than that in the control group (0.15 ± 0.03) µg/L; and the high fluorosis group showed higher level than the low fluorosis group (all P < 0.05). Compared to the control group (131.11 ± 1.95, 111.82 ± 2.39), the protein and mRNA levels of CaN were higher in the low- or high-dose fluorosis groups (142.69 ± 1.17, 157.54 ± 1.88 and 121.28 ± 3.27, 134.63 ± 3.19, respectively), and the high fluorosis group showed higher levels than the low fluorosis group (all P < 0.05). CONCLUSIONS: BGP content could be used as a bone metabolic index in endemic fluorosis disease. Fluoride might up-regulate the mRNA and protein expression of CaN, and the changes in CaN level may be involved in the increase of the bone turnover and could be one of the pathogenetic factors in fluorosis.

The use of myristic acid as a ligand of polyethylenimine/DNA nanoparticles for targeted gene therapy of glioblastoma.

To establish a gene delivery system for brain targeting, a low molecular weight polyethylenimine (PEI(10 K)) was modified with myristic acid (MC), and complexed with DNA, yielding MC-PEI(10 K)/DNA nanoparticles successfully. The nanoparticles were observed to be successfully taken up by the brains of mice. The transfection efficiency of the nanoparticles was then investigated, and both the in vitro and in vivo gene expression of MC-PEI(10 K)/DNA nanoparticles is significantly higher than that of unmodified PEI(10 K)/DNA nanoparticles. The anti-glioblastoma effect of MC-PEI(10 K)/pORF-hTRAIL was demonstrated by the survival time of intracranial U87 glioblastoma-bearing mice. The median survival time of the MC-PEI(10 K)/pORF-hTRAIL group (28 days) was significantly longer than that of the PEI(10 K)/pORF-hTRAIL group (24 days), the MC-PEI(10 K)/pGL(3) group (21 days) and the saline group (22 days). Therefore, our results suggested that MC-PEI(10 K) could be potentially used for brain-targeted gene delivery and in the treatment of glioblastoma.

Imaging beyond the diagnosis: image-guided enzyme/prodrug cancer therapy.

The ideal therapy would target cancer cells while sparing normal tissue. However, in most conventional chemotherapies normal cells are damaged together with cancer cells resulting in the unfortunate side effects. The principle underlying enzyme/prodrug therapy is that a prodrug-activating enzyme is delivered or expressed in tumor tissue following which a non-toxic prodrug is administered systemically. Non-invasive imaging modalities can fill an important niche in guiding prodrug administration when the enzyme concentration is detected to be high in the tumor tissue but low in the normal tissue. Therefore, high therapeutic efficacy with minimized toxic effect can be anticipated. This review introduces the latest developments of molecular imaging in enzyme/prodrug cancer therapies. We focus on the application of imaging modalities including magnetic resonance imaging, position emission tomography and optical imaging in monitoring the enzyme delivery/expression, guiding the prodrug administration and evaluating the real-time therapeutic response in vivo.

Prognostic Role of EGFR/p-EGFR in Patients With Nasopharyngeal Carcinoma: A Meta-Analysis.

BACKGROUND: The prognostic value of epidermal growth factor receptor (EGFR)/phosphorylated EGFR (p-EGFR) expression in nasopharyngeal carcinoma remains controversial. A meta-analysis was performed to investigate prognostic significance of EGFR/p-EGFR expression in patients with nasopharyngeal carcinoma. METHODS: Literatures published before November 2020 were systematically searched in relevant databases, including PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wan fang databases. STATA 13 statistical software was used to analyze the pooled hazard ratio (HR) and 95% confidence interval (CI). Heterogeneity of the studies was examined by I2. Sensitivity and subgroup analysis were performed to explore sources of heterogeneity. The potential publication bias was assessed using both Egger's and Begg's tests. RESULTS: A total of 20 literatures with 1545 patients were included for the meta-analysis. The meta-analysis results suggested that high expression of EGFR was significantly associated with poor overall survival (OS) (HR = 1.70, 95% CI: 1.24-3.15, P = 0.001) and disease-free survival (DFS) (HR = 2.58, 95% CI: 1.87-3.56, P = 0.000). However, it was not significantly associated with progression-free survival (PFS) (HR = 1.85, 95% CI: 0.90-3.82, P = 0.09) and distant metastasis-free survival (DMFS) (HR = 1.39, 95% CI: 0.73-2.67, P = 0.319). The subgroup analysis indicated that patients with EGFR high expression in studies of higher TNM stage (III-IV) ratio had significantly poor OS (HR = 2.27, 95% CI: 1.09-4.73, P = 0.03), but heterogeneity existed in studies (I2 = 95.1%, P = 0.000). Sensitivity analyses revealed that EGFR expression did not significantly affect OS by an individual study solely, indicating there was inherent heterogeneity in OS cohorts. There was no significant heterogeneity among eight studies in the DFS cohorts (I2 = 0%, P = 0.606). There was significant heterogeneity between EGFR expression and DMFS (I2 = 82.8%, P = 0.000). Sub-group analysis in differentiated carcinoma demonstrated a smaller heterogeneity (I2 = 33.2%). In addition, p-EGFR high expression had no significant correlation with OS (HR = 1.00, 95% CI: 0.88-1.14, P = 0.982) and DMFS (HR = 1.21, 95% CI: 0.96-1.52, P = 0.112). The heterogeneity among p-EGFR and OS studies was small (I2 = 21%, P = 0.26). There was no significant heterogeneity in the DMFS cohorts (I2 = 0%, P = 0.497). CONCLUSION: EGFR high-expression was significantly associated with poor OS and DFS, which may serve as a prognostic predictor for nasopharyngeal cancer. SYSTEMATIC REVIEW REGISTRATION: [https://www.crd.york.ac.uk/PROSPERO], identifier [number CRD42021258457].