NIR-triggered thermosensitive polymer brush coating modified intraocular lens for smart prevention of posterior capsular opacification.

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. Drug-eluting intraocular lens (IOLs) is a promising concept of PCO treatment in modern cataract surgery. However, the large dose of drugs in IOL leads to uncontrollable and unpredictable drug release, which inevitably brings risks of overtreatment and ocular toxicity. Herein, a low-power NIR-triggered thermosensitive IOL named IDG@P(NIPAM-co-AA)-IOL is proposed to improve security and prevent PCO by synergetic controlled drug therapy and simultaneous photo-therapy. Thermosensitive polymer brushes Poly(N-isopropylacrylamide-co-Acrylic acid) (P(NIPAM-co-AA)) is prepared on IOL via surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization. Then, Doxorubicin (DOX) and Indocyanine green (ICG) co-loaded Gelatin NPs (IDG NPs) are loaded in P(NIPAM-co-AA) by temperature control. The IDG NPs perform in suit photodynamic & photothermal therapy (PTT&PDT), and the produced heat also provides a trigger for controllable drug therapy with a cascade effect. Such functional IOL shows excellent synergistic drug-phototherapy effect and NIR-triggered drug release behavior. And there is no obvious PCO occurrence in IDG@P(NIPAM-co-AA) IOL under NIR irradiation compared with control group. This proposed IDG@P(NIPAM-co-AA)-IOL serves as a promising platform that combines phototherapy and drug-therapy to enhance the therapeutic potential and medication safety for future clinical application of PCO treatment.

Reducing Target Volumes of Intensity Modulated Radiation Therapy After Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Long-Term Results of a Prospective, Multicenter, Randomized Trial.

PURPOSE: The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC + CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively. RESULTS: After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P = .045) and symptoms including dry mouth (P = .004), sticky saliva (P = .047), and feeling ill (P = .041). CONCLUSIONS: After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.

Augmented cellular uptake and homologous targeting of exosome-based drug loaded IOL for posterior capsular opacification prevention and biosafety improvement.

Posterior capsular opacification (PCO), the most common complication after cataract surgery, is caused by the proliferation, migration and differentiation of residual lens epithelial cells (LECs) on the surface of the intraocular lens (IOL). Although drug-loaded IOLs have been successfully developed, the PCO prevention efficacy is still limited due to the lack of targeting and low bioavailability. In this investigation, an exosome-functionalized drug-loaded IOL was successfully developed for effective PCO prevention utilizing the homologous targeting and high biocompatibility of exosome. The exosomes derived from LECs were collected to load the anti-proliferative drug doxorubicin (Dox) through electroporation and then immobilized on the aminated IOLs surface through electrostatic interaction. In vitro experiments showed that significantly improved cellular uptake of Dox@Exos by LECs was achieved due to the targeting ability of exosome, compared with free Dox, thus resulting in superior anti-proliferation effect. In vivo animal investigations indicated that Dox@Exos-IOLs effectively inhibited the development of PCO and showed excellent intraocular biocompatibility. We believe that this work will provide a targeting strategy for PCO prevention through exosome-functionalized IOL.

Foldable Bulk Anti-adhesive Polyacrylic Intraocular Lens Material Design and Fabrication for Posterior Capsule Opacification Prevention.

Posterior capsular opacification (PCO) is a primary complication after phacoemulsification combined with intraocular lens (IOL) implantation, which is attributed to adhesion, proliferation, and migration of residual lens epithelial cells on IOL. Although surface hydrophilic coating is considered to be a powerful way to inhibit PCO incidence after surgery, it requires complex post-production processes, thus limiting their applicability. In comparison, bulk modification is a stable, effective, and facile IOL synthesis method for PCO prevention. Herein, a new anti-adhesive IOL material was designed and successfully synthesized by radical copolymerization of ethylene glycol phenyl ether methacrylate (EGPEMA) and 2-(2-ethoxyethoxy) ethyl acrylate (EA). The physicochemical properties of P(EGPEMA-co-EA) copolymer materials, including chemical structure, mechanical, thermal, surface, and optical properties, were analyzed by using 1H NMR spectroscopy, FT-IR spectroscopy, tensile test, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), water contact angle measurement, and UV-vis spectroscopy. The elongation at break and the modulus of elasticity of the copolymer were tunable through the change of the composition of monomers. Compared to other components, the tensile results showed that P(EGPEMA-co-EA) materials (70% EGPEMA in mass ratio, F7) are suitable for the preparation of foldable intraocular lens with lower elastic modulus and higher elongation at break. TGA and DSC showed that the material has high thermal stability, and the glass transition temperature of F7 material is 16.1 °C. The water contact angle measurement results showed that the introduction of EA improved the hydrophilicity of the material. The percentage of transmittance of all copolymers at 400-800 nm is above 85%. Then, the biocompatibility of the materials was evaluated by in vitro assay and subcutaneous implantation. Both in vitro results and subcutaneous implantation experiments showed that the designed IOL materials exhibited a good anti-adhesion effect and no cytotoxicity. Finally, phacoemulsification and IOL intraocular implantation were performed, and the in vivo results confirmed the good PCO prevention ability as well as the biocompatibility of the new IOL materials.

A polydopamine-based photodynamic coating on the intraocular lens surface for safer posterior capsule opacification conquering.

Intraocular lens (IOL) is the indispensable implant for cataract surgery. However, posterior capsular opacification (PCO) happens in high incidence after IOL implantation. PCO is caused by adhesion, proliferation, and trans-differentiation of the residual human lens epithelial cells (HLECs). Despite the great achievements in surface coating and antiproliferative drug loading on the intraocular lens (IOL) for effective PCO prevention, the complex fabrication process and potential toxicity of the drugs still limit their clinical applications and commercial mass production. In this investigation, a convenient and efficient photodynamic therapy (PDT) coating fabricated by facile yet economical and practical dopamine self-polymerization was applied to IOL surface modification for PCO prevention. The optical properties of IOL, such as light transmittance, imaging quality and refractive index, remain unchanged after modification. Using an in vitro cell assay, the parameters of PDT were optimized. The PDT coating shows excellent biocompatibility in darkness and eliminates LECs significantly under irradiation. The research on the cell elimination mechanism showed that reactive oxygen species (ROS) mainly induced cell apoptosis. In vivo experiments demonstrated that the implantation of modified IOLs can prevent PCO effectively. As a result, this work provides a safe, simple and effective PDT coating for the IOL surface to reduce the incidence of PCO.

Surface Self-Assembly Construction of Therapeutic Contact Lens with Bacterial "Kill-Releasing" and Drug-Reloading Capabilities for Efficient Bacterial Keratitis Treatment.

Bacterial keratitis, an ophthalmic emergency, can cause corneal perforation and even endophthalmitis, thus leading to severe visual impairment. To achieve effective treatment of bacterial keratitis, good bioavailability of antimicrobial drugs on the ocular surface is desired. In this investigation, a layer-by-layer (LBL) self-assembly combined with the host-guest recognition was used to construct an antibacterial coating on the surface of corneal contact lens (CLs) to improve drug bioavailability and achieve successful treatment of bacterial keratitis. First, a radical copolymerization of acrylic acid (AA) and 1-adamantan-1-ylmethyl acrylate (AdA) was carried out to synthesize a polyanionic copolymer P(AA-co-AdA) (defined as PAcA). Then, PAcA copolymer combined with poly(ethyleneimine) (PEI) was used for a layer-by-layer (LBL) self-assembly to fabricate multilayer films on the surface of CLs. An antibacterial conjugate, ß-cyclodextrin-levofloxacin (ß-CD-LEV), was successfully synthesized and utilized to generate antibacterial coating through a host-guest interaction between AdA and ß-CD-LEV. The antibacterial ability and treatment effect of bacterial keratitis was evaluated by in vitro assay and in vivo test in an animal model of staphylococcal keratitis, demonstrating that the antibacterial coating had good antibacterial and germicidal efficacy both in vivo and in vitro. We believe that this work will provide a promising strategy for the treatment of bacterial keratitis.

Bioinformatics Analysis Predicts hsa_circ_0026337/miR-197-3p as a Potential Oncogenic ceRNA Network for Non-Small Cell Lung Cancers.

BACKGROUND: Circular RNAs (circRNAs) play an essential role in developing tumors, but their role in Non- Small Cell Lung Cancer (NSCLC) is unclear. Thus, the present study explored the possible molecular mechanism of circRNAs in NSCLC. METHODS: Three circular RNA (circRNA) microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differential expressions of circRNAs (DECs) were identified in NSCLC tissue and compared to adjacent healthy tissue. The online cancer-specific circRNA database (CSCD) was used for the analysis of the DECs function. Protein-Protein Interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Cytoscape and UALCAN were used to predict the critical nodes and perform patient survival analysis, respectively. The interaction between the DECs, the predicted miRNAs, and hub genes was also determined. Finally, the circRNA-miRNA-mRNA network was established. RESULTS: The expression of hsa_circ_0049271, hsa_circ_0026337, hsa_circ_0043256, and hsa_circ_0008234 was decreased in NSCLC tissues. The Encyclopedia of RNA Interactomes (ENCORI) and CSCD database results showed that hsa_circ_0026337 was found to sponge with miR-1193, miR-197-3p, miR-3605-5p, miR-433-3p and miR-652-3p, and hsa_circ_0043256 to sponge with miR-1252-5p, miR-494-3p and miR-558, respectively. Subsequently, 100 mRNAs were predicted to bind with these seven miRNA response elements (MREs). The GO analysis and KEGG pathway revealed that these 100 MREs might be involved in "histone deacetylase binding" and "cellular senescence." PPI network and Cytoscape identified the top ten hub genes. Survival analysis data showed that the low expression of hsa_circ_0026337 was significantly associated with shortened survival time in NSCLC (P = 0.037), which increased the expression level of hsa-miR-197-3p, thereby inhibiting the translation of specific proteins. CONCLUSION: This study examined the circRNA-miRNA-mRNA regulatory network associated with NSCLC and explored the potential functions of DECs in the network to elucidate the mechanisms underlying disease progression in NSCLC.

Surface Modification of Intraocular Lens with Hydrophilic Poly(Sulfobetaine Methacrylate) Brush for Posterior Capsular Opacification Prevention.

Purpose: The intraocular lens (IOL) is a common, yet important, implantable device used in treatment of cataract in clinics. However, the unexpected adhesion of postoperative residual lens epithelial cells (LECs) often causes serious complications, such as posterior capsular opacification (PCO), which lead to vision loss again. In this investigation, a poly(sulfobetaine methacrylate) (PSBMA) brush coating was fabricated on an IOL to generate a hydrophilic surface coating on the IOL for enhanced cell adhesion resistance so as to decrease PCO incidence. Methods: The PSBMA brush coating on the IOL surface was fabricated using surface-initiated reversible addition-fragmentation chain transfer polymerization. X-ray photoelectron spectroscopy (XPS) was used to demonstrate the surface coating preparation. The water contact angle (WCA) measurement was used to test surface hydrophilicity. In vitro LEC culture was use to evaluate the cell behavior on the IOL material surfaces, with or without PSBMA coating modification. Finally, animal cataract surgeries were carried out to evaluate in vivo biocompatibilities and anti-PCO effects. Results: The XPS and WCA measurements illustrate successful surface modification and good surface hydrophilicity. The in vitro cell culture results show that the hydrophilic PSBMA polymer brush coating evidently decreases adhesion and proliferation of LECs. Results of the in vivo cataract surgery with intraocular implantation show that PSBMA modification on the IOL surface does not induce side effects in nearby tissues, whereas posterior capsular hyperplasia can be evidently reduced. Conclusion: The PSBMA brush surface-modified IOL has good in vivo biocompatibility and it can effectively reduce the incidence of postoperative PCO.

Enhanced PCO prevention of drug eluting IOLs via endocytosis and autophagy effects of a PAMAM dendrimer.

Drug-loaded intraocular lenses (IOLs) have received considerable attention in treating complications that arise after cataract surgery, especially posterior capsular opacification (PCO). However, for a better therapeutic effect, the drug concentration in IOLs usually needs to be increased. Herein, we developed multilayer (doxorubicin (DOX)@polyaminoamide (PAMAM) (D@P)/heparin sodium (HEP))5 modified IOLs, which efficiently enhance the inhibitory effect on PCO using the enhanced autophagy effect of a cationic PAMAM. The chemotherapeutic drug DOX was encapsulated in PAMAM to formulate cationic DOX@PAMAM nanoparticles. Subsequently, negatively charged HEP and D@P nanoparticles (NPs) were assembled on the aminated artificial IOL surface using the layer-by-layer (LBL) assembly technique. The (D@P/HEP)5 IOLs were implanted into rabbit eyes to evaluate the prevention of PCO. In vitro and in vivo research studies showed that the D@P NPs exhibited enhanced cellular uptake owing to the cell-penetrating cationic characteristics, while demonstrating enhanced autophagy. D@P NPs are more effective at the same DOX concentration when compared to free DOX. Multilayer-modified (D@P/HEP)5 IOLs can efficiently inhibit PCO after cataract surgery. This study provides a strategy for improving the therapeutic effect of antiproliferative drug DOX by using a cationic dendrimer, which, in turn, increases the level of autophagy of cells. These LBL-based multilayer IOLs have broad application prospects in the treatment of complications after cataract surgery.

Antiproliferative drug-loaded multi-functionalized intraocular lens for reducing posterior capsular opacification.

Posterior capsule opacification (PCO) is one of the most frequent complications in cataract surgery and likely to cause the second loss of vision. Proliferation and migration of postoperative remnants of lens epithelial cells (LECs) on the implanted intraocular lens (IOL) are the leading causes of PCO. Antiproliferative drugs can be an effective solution but also possess some problems including sudden release and accompanying adverse effects to surrounding normal tissues, which greatly limit the clinical trials. In this study, an antiproliferative drug Paclitaxel (Pac) -sustained released hyaluronic acid (HA) and chitosan (CHI) multilayer modified IOL with postoperatively long-term PCO prevention was fabricated via layer by layer (LbL) technique. Quartz crystal microbalance with dissipation monitoring (QCM-D) result shows that HA-Pac/CHI multilayer is modified onto IOL material via LbL technique successfully. The HA-Pac/CHI multilayer coating greatly improves the hydrophilicity of the IOL material surfaces without change the transmittance significantly, whereas the proliferation of LECs is distinctly reduced on the HA-Pac/CHI multilayer-modified surfaces. The drug release in vitro reveals that the multilayer modified IOL material is stable under physiological condition and has good sustained drug release property. All these results demonstrate that HA-Pac/CHI multilayer modified IOL material can effectively inhibit LECs proliferation which provides a novel approach for reducing of PCO incidence in clinical.

Are Poly(amidoamine) Dendrimers Safe for Ocular Applications? Toxicological Evaluation in Ocular Cells and Tissues.

Purpose: The human eye is a sophisticated and sensitive sensory organ. Because of the existence of the blood-ocular barrier and corneal-scleral barrier, safe and efficient ocular drug delivery system is highly desired; yet, it remains an unsolved issue. Due to the unique structure and drug loading property, Poly(amidoamine) (PAMAM) has received much attention in the ocular drug delivery investigation. Herein, we evaluated the ocular cytotoxicity and biosafety of PAMAM dendrimers. Methods: The ocular cytotoxicity and biosafety of PAMAM dendrimers were evaluated by conducting in vitro and in vivo experiments on ocular systems. The in vitro effect of PAMAM dendrimer of different generations (G4.0, G5.0, and G6.0) and concentrations on ocular cell metabolism, apoptosis, and oxidative damage were quantitatively assessed. In vivo biosafety of PAMAM dendrimers were further investigated on intraocular tissue by ocular irritation and intravitreal injection approaches. Results: It is found that that the cytotoxicity of PAMAM was time and generation dependent. PAMAM at a concentration below 50 µg/mL had minimal impact on the ocular tissue, whereas it caused apparent damage when above 50 µg/mL in the investigated situation. Further, our in vivo results showed that higher concentration of dendrimer (100 µg/mL) was associated with functional impairment demonstrated via optical coherence tomography and electroretinogram, although macroscopic structural changes were absent in fundus and histopathological studies. Overall, a higher concentration of PAMAM, such as above 50 µg/mL, may cause ocular functional damage. Conclusion: The PAMAM at the concentrations lower than 50 µg/mL showed good biocompatibility and biosafety in human ocular cells and tissues.

Antiangiogenic effects of recombinant human endostatin in lung cancers.

Antiangiogenic therapy, as a new anticancer method, can improve the anticancer effect of traditional therapies. Different antiangiogenic drugs may have different vascular normalization time windows. Whether the antiangiogenic treatment is within the vascular normalization time window is very important in the treatment of cancers. Previous studies have indicated that recombinant human endostatin (rh­ES) can transiently normalize tumor microvessels. Yet the molecular mechanism and the time window of rh­ES remains unclear. The aim of the present study was to explore the optimal time window and molecular mechanism of rh­ES in inhibiting Lewis lung cancer (LLC). By comparatively accessing the changes in microvascular and hypoxic conditions of tumors in host mice treated with rh­ES or saline for different days, the authors aimed to investigate the best administration time of rh­ES treatment on human lung cancers and obtain a better understanding concerning the involved molecular mechanism. A total of 40 C57/BL6 mice with LLC xenografts were randomly divided into normal saline (NS) and rh­ES groups (20 mice/group). 0.2 ml NS or 5 mg/kg rh­ES were administrated via intraperitoneal injection (i.p.) into each mouse each day during the 9­day experiment. A total of 5 mice from each group were sacrificed at day 2, 4, 6 or 9. CA9 and RGS5 expression levels of both groups were compared using immunohistochemistry, reverse transcription­quantitative polymerase chain reaction and ELISA. Rh­ES caused vascular normalization and improved hypoxia at days 4 and 6. Compared with the control (NS) group, both CA9 and RGS5 expression in rh­ES group were significantly decreased at days 4 and 6 (P<0.05), while no significant change between two groups was observed at days 2 and 9. Rh­ES can induce transient tumor vascular normalization and improves tissue hypoxia in LLC tumors. The vascular normalization window is accompanied by the reduction in RGS5 and CA expression.

Is IMRT Superior or Inferior to 3DCRT in Radiotherapy for NSCLC? A Meta-Analysis.

INTRODUCTION: There are no adequate data to determine whether intensity-modulated radiotherapy (IMRT) is superior to three-dimensional conformal radiotherapy (3DCRT) in the treatment of non-small cell lung cancer (NSCLC). This meta-analysis was conducted to compare the clinical outcomes of IMRT and 3DCRT in the treatment of NSCLC. METHODS: No exclusions were made based on types of study design. We performed a literature search in PubMed, EMBASE and the Cochrane library databases from their inceptions to April 30, 2015. The overall survival (OS) and relative risk (RR) of radiation pneumonitis and radiation oesophagitis were evaluated. Two authors independently assessed the methodological quality and extracted data. Publication bias was evaluated by funnel plot using Egger's test results. RESULTS: From the literature search, 10 retrospective studies were collected, and of those, 5 (12,896 patients) were selected for OS analysis, 4 (981 patients) were selected for radiation pneumonitis analysis, and 4 (1339 patients) were selected for radiation oesophagitis analysis. Cox multivariate proportional hazards models revealed that 3DCRT and IMRT had similar OS (HR = 0.96, P = 0.477) but that IMRT reduced the incidence of grade 2 radiation pneumonitis (RR = 0.74, P = 0.009) and increased the incidence of grade 3 radiation oesophagitis (RR = 2.47, P = 0.000). CONCLUSIONS: OS of IMRT for NSCLC is not inferior to that of 3DCRT, but IMRT significantly reduces the risk of radiation pneumonitis and increases the risk of radiation oesophagitis compared to 3DCRT.

Role of Gemcitabine and Pemetrexed as Maintenance Therapy in Advanced NSCLC: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Gemcitabine and pemetrexed have been used as maintenance therapy. However, few systematic reviews and meta-analyses have assessed their effects in the newest studies. This systematic review and meta-analysis were conducted to assess the role of gemcitabine and pemetrexed in the maintenance treatment of non-small-cell lung carcinoma (NSCLC). METHODS: We performed a literature search using PubMed, EMBASE and Cochrane library databases from their inceptions to September 16, 2015. We also searched the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN) databases from 2008 to 2015. Two authors independently extracted the data. The Cochrane Collaboration's risk of bias graph was used to assess the risk of bias. The GRADE system was used to assess the grading of evidence, and a meta-analysis was conducted using Stata 11.0 software. RESULTS: Eleven randomized controlled trial (RCT) studies were collected. Ten studies were included in the meta-analysis and divided into the following 4 groups: gemcitabine vs. best supportive care (BSC)/observation, pemetrexed vs. BSC/placebo, pemetrexed + bevacizumab vs. bevacizumab and pemetrexed vs. bevacizumab. Gemcitabine exhibited significantly improved progression-free survival (PFS) compared with BSC (hazard ratio (HR) = 0.62, p = 0.000). Pemetrexed exhibited significantly improved PFS (HR = 0.54, p = 0.000) and OS (HR = 0.75, p = 0.000) compared with BSC. Pemetrexed + bevacizumab almost exhibited significantly improved PFS (HR = 0.71, p = 0.051) compared with bevacizumab. Pemetrexed exhibited no improvement in PFS or overall survival (OS) compared with bevacizumab. Regarding the grade, the GRADE system indicated that the gemcitabine group was "MODERATE", the pemetrexed group was "HIGH", and both the pemetrexed + bevacizumab vs. bevacizumab groups and pemetrexed vs. B groups were "LOW". CONCLUSIONS: Gemcitabine or pemetrexed compared with BSC/observation/placebo significantly improved PFS or OS. Whether pemetrexed + bevacizumab compared with bevacizumab alone significantly improves PFS requires further investigation.

Efficacy of tamoxifen in combination with docetaxel in patients with advanced non-small-cell lung cancer pretreated with platinum-based chemotherapy.

The aim of this study was to evaluate the efficacy and safety of the combination of docetaxel (TXT) plus tamoxifen (TAM) in advanced non-small-cell lung cancer (NSCLC) patients who had received platinum-based first-line chemotherapy. A total of 120 advanced NSCLC patients pretreated with platinum-based chemotherapy were randomized into two treatment groups (the TXT and TXT+TAM groups) in a 1 : 1 ratio. Reversal of P-glycoprotein (P-gp) expression, tumor response, progression-free survival, overall survival, and safety were evaluated on an intention-to-treat basis. The median number of cycles of allocated chemotherapy was four in each treatment group (range: 2-6 cycles). The overall response rate and disease control rate in the TXT+TAM group were significantly higher than those in the TXT group (36.7 vs. 15.0% for overall response rate, P=0.007; 85.0 vs. 68.3% for disease control rate, P=0.031). The combination of TXT and TAM could effectively reverse P-gp expression in tumor tissues and provide a significant survival benefit for advanced NSCLC patients compared with TXT alone (11.6 vs. 9.1 months, P=0.030). In addition, in the TXT+TAM group, patients achieving P-gp reversal had a significantly greater median progression-free survival and overall survival than nonreversal patients. Furthermore, the combined therapy showed a safety profile comparable to that of TXT. The combination of TXT and TAM may be an effective and safe treatment option for advanced NSCLC patients who have already developed P-gp-mediated multidrug resistance.

Primary desmoplastic small round cell tumor of the testis: A case report and review of the literature.

Desmoplastic small round cell tumors (DSRCTs) are extremely rare and mainly affect adolescents and young adults. The tumors are usually involved with the abdominal area and/or the pelvic peritoneum. Only a small number of cases have been reported concerning DSRCTs of the testicular region. The present study reports a case of DSRCT of the testis with radical orchectomy and systemic chemotherapy, leaving the patient disease-free for 14 months. However, the patient died of multiple metastasis 12 months later. Furthermore there is a review of the English literature to analyze the incidence, site of origin, imaging and pathological characteristics of DSRCT.

[Prognostic value of MACC1 and c-met expressions in non-small cell lung cancer].

BACKGROUND: It has been proven that metastasis-associated in colon cancer 1 (MACC1) is a new gene that is related to the invasion and metastasis of tumors. MACC1 also regulates c-met expression. The aim of this study is to explore the expressions of MACC1 and hepatocyte growth factor receptor (c-met), and its relationship with invasion, metastasis, and prognosis of non-small cell lung cancer (NSCLC). METHODS: MACC1 and c-met expressions were detected in 103 cases of NSCLC and 40 cases of neighboring normal lung cancer tissue using immunohistochemistry. RESULTS: MACC1 and c-met expressions were significantly higher in lung cancer tissues than that in neighboring normal tissue (P<0.001). MACC1 and c-met expressions were associated with poor differentiation, advanced T stages, lymph node metastasis, and advanced TNM stages (P<0.05) of NSCLC, but not with sex, age, smoking, and histological classification (P>0.05). In addition, a positive correlation between MACC1 and c-met expressions was observed (r=0.403, P<0.001). The result from the Kaplan-Meier survival analysis showed that the five-year survival rate in patients with positive MACC1 and c-met expressions was remarkanly lower than that in patients with negative expressions (P<0.05). The result from the Cox regression analysis showed that MACC1 expression was an independent prognostic factor for NSCLC (P=0.026). CONCLUSIONS: MACC1 and c-met have an important function in the differentiation, invasion, and metastasis of NSCLC. MACC1 and c-met have poor prognosis in patients with NSCLC. Moreover, MACC1 expression is an independent prognostic factor for NSCLC.

[The clinical signifcance of expression of ERCC1 and PkCalpha in non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: Excision repair cross-complementing 1 (Excision-Repair Cross-Complementing 1, ERCC1), an important member of the DNA repair gene family, plays a key role in nucleotide excision repair and apoptosis of tumor cells. Protein kinase C-alpha (Protein kinase C, PKCalpha), an isozyme in protein kinase C family, is an important signaling molecule in signal transduction pathways of tumors, which has been implicated in malignant transformation and proliferation. The aim of this study was to explore the clinical significance of ERCC1 and PKCalpha in non-small cell lung cancer (NSCLC). METHODS: The expression of ERCC1 and PKCalpha were examined by immunohistochemistry (IHC) in the specimens of 51 cases of NSCLC patients tissue and 21 cases of paracancerous tissue. The relationship between detected data and patients' clinical parameters was analyzed by SPSS 13.0 software. RESULTS: The positive expression rate of ERCC1 and PKCalpha in NSCLC tissues was significantly higher than paracancerous tissues (P < 0.05). Expression of ERCC1 was closely related to clinical stage and N stage. The positive rate of ERCC1 was higher in III+IV or N1+N2 stage patients compared with I+II or N0 stage (P = 0.011, P = 0.015). We also found that 5-year survival of negative group of ERCC1 was remarkably higher than that of positive group by chi2 test (P < 0.05). Expression of ERCC1 was positively correlative to PKCalpha by Spearman's correlation analysis (r = 0.425, P = 0.002) in NSCLC. CONCLUSION: The results suggest ERCC1 and PKCalpha might be correlated with the development of NSCLC. ERCC1 might be related to prognosis of NSCLC. There might be existed a mechanism of coordination or regulation between ERCC1 and PKCalpha.