Discovery and Feasibility Study of Medical Fluorophore 33 as a Novel Theranostic Agent.

Fluorescent dyes have garnered significant attention as theranostic platforms owing to their inherent characteristics. In this study, we present the discovery of Medical Fluorophore 33 (MF33), a novel and potent theranostic agent with a phenaleno-isoquinolinium salt structure that can serve as a cancer therapeutic strategy. The synthesis of MF33 is readily achievable through a simple Rh(III)-catalyzed reaction. Moreover, MF33 displayed strong fluorescence signals, excellent microsomal stability, and high biocompatibility in vivo. It induces significant apoptosis in cancer cells via the p53/p21/caspase-3 signaling pathway, leading to selective cytotoxicity in various cancer cells. In vivo fluorescence imaging with MF33 enabled the visualization of sentinel lymph nodes in living mice. Notably, repeated intraperitoneal administration of MF33 resulted in antitumor activity in mice with colorectal cancer. Collectively, our findings suggest that phenaleno-isoquinolinium salt-based MF33 is a viable theranostic agent for biomedical imaging and cancer treatment.

Tract seeding in indwelling pleural catheter placement for the drainage of malignant pleural effusions: Incidence and related clinical and imaging factors.

BACKGROUND: The incidence of tract seeding after the placement of indwelling pleural catheter (IPC) for malignant pleural effusion drainage has been variable in the literature. RESEARCH QUESTION: To evaluate the incidence of IPC-related cancer tract seeding and find out related demographic, clinical or imaging factors to the tract seeding. STUDY DESIGN AND METHODS: This retrospective study included 124 consecutive patients seen between January 2011 and December 2021 who underwent IPC placement for malignant pleural effusion drainage. Chest radiographs before IPC placement and serial chest CT studies were obtained. One patient was diagnosed pathologically, and the other patients were diagnosed as tract seeding radiologically. The incidence of and related factors to tract seeding were assessed by reviewing medical records and imaging studies. RESULTS: The incidence of IPC tract seeding was 21.7% (27 of 124 malignant effusions). Of 27 patients, 15 had primary lung cancer and remaining 12 had extra-thoracic malignancy. Adenocarcinoma (19 of 27, 70.3%) either from the lung (N = 12) or extra-thoracic malignancy (N = 7) was the most common cell type. Mean time elapsed until tract seeding occurrence after IPC placement was 96 days (ranges; 28-306 days). The survival in seeding group after IPC placement was 185 days (ranges, 32-457 days). On odd ratio analysis, the presence of mediastinal pleural thickening (OR [95% CI]; 9.79 (2.67-35.84), p = 0.001) was significantly related to the occurrence of tract seeding. Neither tumor volume within pleural space (p = 0.168), duration of IPC indwelling (p = 0.142), days of survival after IPC placement (p = 0.26), nor pleural effusion amount (p = 0.481) was related to the tract seeding. INTERPRETATION: IPC tract seeding is seen in 27 (21.7%) of 124 malignant pleural effusion patients, particularly with adenocarcinoma cytology. CT features of mediastinal pleural thickening are related to the occurrence of tract seeding.

High-Intensity Focused Ultrasound Therapy Versus Coblation for the Treatment of Inferior Turbinate Hypertrophy: A Clinical Trial.

OBJECTIVES: To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) therapy with coblation for the treatment of inferior turbinate hypertrophy (ITH). METHODS: In this randomized controlled clinical trial, 20 patients underwent inferior turbinate surgery, which consisted of either HIFU or coblation therapy. Efficacy, safety, and tolerability were evaluated by subjective symptom scores, acoustic rhinometry, and nasal endoscopy. RESULTS: The modified nasal obstruction symptom evaluation (NOSE) score and nasal obstruction visual analog scale (NO-VAS) significantly decreased in both groups 12 weeks postoperatively. The between-group differences in the evaluation scores were not statistically significant. On nasal endoscopy, the HIFU patients showed improvements in mucosal swelling sooner than the patients undergoing coblation therapy. Nasal crusting significantly increased in the patients undergoing coblation compared to the patients undergoing HIFU therapy until postoperative week 4. Mucosal preservation was superior in the HIFU patients. Although HIFU was less painful than coblation therapy during the procedure, the difference was not significant (4.9 vs. 6.3, P=0.143). The difference in global satisfaction between the two groups was not statistically significant, although satisfaction was slightly higher among the HIFU patients than among the coblation patients (4.6 vs. 4.1, P=0.393). CONCLUSION: HIFU provided results similar to those of coblation therapy for patients with nasal obstruction due to ITH, but HIFU therapy caused less discomfort during the procedure. HIFU therapy appears to be a good noninvasive alternative to the current surgical modalities for ITH.

A synergistic strategy to remove hazardous water pollutants by mimicking burdock flower morphology structures of iron oxide phases.

Artificially mimicking structures/morphologies available in the nature to develop multifunctional materials for catalysis is receiving greater attention. Particularly, the burdock flower morphology, which has a hollow-globe surrounded by spiky sheets, represents a multifunctional structure helpful in adsorption as well as intercalation of molecules. Given this, we have strategically developed a robust microwave (MW) bubble-template process to achieve highly uniform α-Fe2O3 and carbon-enriched Fe3O4 (Fe3O4@C) phases resembling the characteristics of spiky hollow burdock morphologies. The utilization of the MW bubble-templates as a pretreatment to the iron-based precursor solution helps in producing hollowed open-space ferrous glycolate burdock flower morphology with rapid production rate and without any addition of extra agents. Such burdock flower structures remain intact even after annealing in air/N2 ambiance providing highly photoactive α-Fe2O3 or magnetic Fe3O4@C, respectively. Utilizing the hollow burdock flower structures together with the individual photo/magnetic properties of iron oxide phases, a dual-layer filter was designed to remove hazardous dye molecules from water, which efficiently photodegraded (99.2 %) in natural sunlight as well as showed excellent adsorption (99.7 %) within minutes. Comparatively, a lower catalytic activity using simple iron oxide nanoparticles, closed, and faded burdock morphologies were seen. Hence, the high catalytic activity in removing the dye molecules, retention of structural phases after repeated use, and strong durability were a result of the synergetic effect of photo/magnetic properties, activated surface/spiky open burdock structure.

Discovery of novel phenaleno isoquinolinium-based fluorescence imaging agents for sentinel lymph node mapping.

Fluorescence imaging agents have recently received huge attention due to their important role in disease diagnostics. However, the intrinsic problems of these probes, such as complex synthetic routes and high molecular weight, remain challenging. Here, we developed novel phenaleno isoquinolinium-based fluorescent agents, Medical Fluorophores 37-41 (MF37-41), applicable to the quantitative and sensitive detection of sentinel lymph nodes (SLNs). These imaging agents showed no adverse effects on the proliferation of immune and normal cells and did not induce in vivo toxicity. In vivo fluorescence lifetime imaging demonstrated the accumulation of phenaleno isoquinolinium salts in the SLNs of nude mice within 15 min postinjection, consistent with our biodistribution findings. These results suggest that phenaleno isoquinolinium salts are feasible fluorescence imaging agents that can be used as potential lymphatic tracers.

Novel quinoline-based fluorescent bioimaging probe, KSNP117, for sentinel lymph node mapping.

Fluorescent imaging agents with biocompatibility and high sensitivity are urgently required for the accurate detection of sentinel lymph nodes (SLNs). Herein, we report the design of a novel quinoline-based fluorescent probe, designated KSNP117, which can be applied as a biomedical imaging agent in the sensitive and quantitative detection of SLNs. KSNP117 exerted no adverse effects on the proliferation of ovary and immune cells and also showed excellent serum stability with photo-brightening effects. In vivo fluorescent imaging revealed the accumulation of KSNP117 in the SLNs of nude mice within 10 min post injection, without in vivo toxicity, which was consistent with the findings of ex vivo imaging. These results support the potential of KSNP117 as a promising lymphatic tracer for biomedical imaging applications.

Antioxidative and anti-inflammatory activity of psiguadial B and its halogenated analogues as potential neuroprotective agents.

Psiguadial B (8), and its fluoro- (8a), chloro- (8b), and bromo- (8c) derivatives were synthesized using a sodium acetate-catalyzed single step coupling of three components: ß-caryophyllene (5), diformylphloroglucinol (11), and benzaldehyde (12). These compounds efficiently and dose-dependently decreased H2O2-induced cell death, a quantitative marker of cell death, in primary cultures of mouse cortical neurons. Psiguadial B also decreased neuronal death and accumulation of ROS induced by FeCl2 in cortical cultures. The in vitro effects of these compounds in lipopolysaccharide (LPS)-induced expression of nitric oxide (NO), and TNF-α and IL-6 by suppressing the NF-κB pathway in immune cells demonstrated their antioxidative and anti-inflammatory activity. The present findings warrant further research on the development of psiguadial B-based neuroprotective agents for the treatment of neurodegenerative diseases, acute brain injuries and immunological disorders.

CD5L as an Extracellular Vesicle-Derived Biomarker for Liquid Biopsy of Lung Cancer.

Cancer screening and diagnosis can be achieved by analyzing specific molecules within serum-derived extracellular vesicles (EVs). This study sought to profile EV-derived proteins to identify potential lung cancer biomarkers. EVs were isolated from 80 serum samples from healthy individuals and cancer patients via polyethylene glycol (PEG)-based precipitation and immunoaffinity separation using antibodies against CD9, CD63, CD81, and EpCAM. Proteomic analysis was performed using 2-D gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). The expression of proteins that were differentially upregulated in the EVs or tissue of lung cancer samples was validated by Western blotting. The area under the curve (AUC) was calculated to assess the predictability of each differentially expressed protein (DEP) for lung cancer. A total of 55 upregulated protein spots were selected, seven of which (CD5L, CLEC3B, ITIH4, SERFINF1, SAA4, SERFINC1, and C20ORF3) were found to be expressed at high levels in patient-derived EVs by Western blotting. Meanwhile, only the expression of EV CD5L correlated with that in cancer tissues. CD5L also demonstrated the highest AUC value (0.943) and was found to be the core regulator in a pathway related to cell dysfunction. Cumulatively, these results show that EV-derived CD5L may represent a potential biomarker-detected via a liquid biopsy-for the noninvasive diagnosis of lung cancer.

Four-dimensional inverse-geometry computed tomography: a preliminary study.

This study introduces and evaluates respiratory-correlated four-dimensional (4D) inverse geometry computed tomography (IGCT). The projection data of the IGCT were acquired in a single gantry rotation over 120 s. Three virtual phantoms-static Defrise, 4D Shepp-Logan, and 4D extended cardiac-torso (XCAT)-were used to obtain projection data for the IGCT and cone-beam computed tomography (CBCT). The projection acquisition parameters were determined to eliminate vacancies in the Radon space for an accurate rebinning process. Phase-based sorting was conducted within 10 phase bins, and the sorted projection data were binned into a cone beam geometry. Finally, Feldkamp-Davis-Kress reconstruction was conducted independently at each phase. The reconstructed images were compared using the structural similarity index measure (SSIM) and root mean square error (RMSE). The vertical profile of the Defrise reconstruction image was uniform, and the cone beam artefact was reduced in the IGCT image. Under an ideal projection acquisition condition, the mean coronal plane SSIMs of the Shepp-Logan and 4D XCAT phantoms were 0.899 and 0.706, respectively, which were higher than those of the CBCT (0.784 and 0.623, respectively). Similarly, the mean RMSEs of the coronal plane IGCT (0.036 and 0.158) exhibited an improvement over those of the CBCT (0.165 and 0.261, respectively). The mean standard deviations of the SSIM and RMSE were lower for IGCT than for CBCT. In particular, the SSIM and RMSE of the sagittal and coronal planes of the Shepp-Logan IGCT images were stable in all phase bins; however, those of the CBCT changed depending on the phase bins. Poor image quality was observed for IGCT under inappropriate conditions. This was caused by a vacancy in the Radon space, owing to an inappropriate scan setting. Overall, the proposed 4D IGCT exhibited better image quality than conventional CBCT.

Cardiac Papillary Fibroelastoma in Left Ventricular Trabeculation as a Potential Cause of Cerebral Infarction: A Case Report.

Cardiac papillary fibroelastoma (CPF) is the second or third most common primary cardiac tumor. Although histologically benign, it can cause serious symptoms depending on its location of occurrence, size, and motility. Herein, we report CPF in the left ventricular trabeculation as a potential cause of cerebral infarction.

Facile synthesis of economical feasible fly ash-based zeolite-supported nano zerovalent iron and nickel bimetallic composite for the potential removal of heavy metals from industrial effluents.

Heavy metals contamination of water is one of the environmental issue globally. Thus prepared fly ash-based zeolite (FZA)-supported nano zerovalent iron and nickel (nZVI/Ni@FZA) bimetallic composite from low-cost fly ash waste for the potential treatment of anion (Cr(VI) and cation Cu(II)) heavy metals from industrial effluents at pH 3 and 5, respectively in this study. The systematic interaction between FZA and nZVI/Ni and the adsorptive removal mechanism was studied. The mean surface area of the nZVI/Ni@FZA (154.11 m2/g) was much greater than that of the FZA (46.6 m2/g) and nZVI (4.76 m2/g) independently, as determined by BET-N2 measurements. The effect of influence factors on the removal of Cr(VI) and Cu(II) by nZVI/Ni@FZA, such as pH effect, initial concentration effect, time effect, temperature effect, coexisting metals, and ionic strength, and cumulative loading ability, were discussed. The maximum adsorption capacity of nZVI/Ni@FZA was 48.31 mg/g and 147.06 mg/g towards Cr(VI) and Cu(II), respectively. These were higher than those of nZVI@FZA and FZA. It demonstrated that Ni could play an important role in enhancing the reduction ability of nZVI. Furthermore, isothermal and kinetic results revealed that both heavy metal adsorption processes were rate limiting monolayer Langmuir adsorption on homogeneous surfaces. Thermodynamic results suggested that the adsorptive removal of metal ions was endothermic with spontaneity. The applicability of nZVI/Ni@FZA on real industrial wastewater treatment results demonstrate that the concentration of heavy metals were removed under the acceptable standard levels. Further the adsorption capacity of nZVI/Ni@FZA was higher than the nZVI@FZA and FZA. The overall results demonstrated that nZVI/Ni@FZA was a promising, efficient, and economically feasible sorbent for potential wastewater treatment. Moreover this is first report on the preparation nZVI/Ni@FZA bimetallic composite.

Dose Super-Resolution in Prostate Volumetric Modulated Arc Therapy Using Cascaded Deep Learning Networks.

PURPOSE: This study proposes a cascaded network model for generating high-resolution doses (i.e., a 1 mm grid) from low-resolution doses (i.e., ≥3 mm grids) with reduced computation time. METHODS: Using the anisotropic analytical algorithm with three grid sizes (1, 3, and 5 mm) and the Acuros XB algorithm with two grid sizes (1 and 3 mm), dose distributions were calculated for volumetric modulated arc therapy plans for 73 prostate cancer patients. Our cascaded network model consisted of a hierarchically densely connected U-net (HD U-net) and a residual dense network (RDN), which were trained separately following a two-dimensional slice-by-slice procedure. The first network (HD U-net) predicted the downsampled high-resolution dose (generated through bicubic downsampling of the baseline high-resolution dose) using the low-resolution dose; subsequently, the second network (RDN) predicted the high-resolution dose from the output of the first network. Further, the predicted high-resolution dose was converted to its absolute value. We quantified the network performance using the spatial/dosimetric parameters (dice similarity coefficient, mean dose, maximum dose, minimum dose, homogeneity index, conformity index, and V95%, V70%, V50%, and V30%) for the low-resolution and predicted high-resolution doses relative to the baseline high-resolution dose. Gamma analysis (between the baseline dose and the low-resolution dose/predicted high-resolution dose) was performed with a 2%/2 mm criterion and 10% threshold. RESULTS: The average computation time to predict a high-resolution axial dose plane was <0.02 s. The dice similarity coefficient values for the predicted doses were closer to 1 when compared to those for the low-resolution doses. Most of the dosimetric parameters for the predicted doses agreed more closely with those for the baseline than for the low-resolution doses. In most of the parameters, no significant differences (p-value of >0.05) between the baseline and predicted doses were observed. The gamma passing rates for the predicted high-resolution does were higher than those for the low-resolution doses. CONCLUSION: The proposed model accurately predicted high-resolution doses for the same dose calculation algorithm. Our model uses only dose data as the input without additional data, which provides advantages of convenience to user over other dose super-resolution methods.

Mechanoadaptive organization of stress fiber subtypes in epithelial cells under cyclic stretches and stretch release.

Cyclic stretch applied to cells induces the reorganization of stress fibers. However, the correlation between the reorganization of stress fiber subtypes and strain-dependent responses of the cytoplasm and nucleus has remained unclear. Here, we investigated the dynamic involvement of stress fiber subtypes in the orientation and elongation of cyclically stretched epithelial cells. We applied uniaxial cyclic stretches at 5%, 10%, and 15% strains to cells followed by the release of the mechanical stretch. Dorsal, transverse arcs, and peripheral stress fibers were mainly involved in the cytoplasm responses whereas perinuclear cap fibers were associated with the reorientation and elongation of the nucleus. Dorsal stress fibers and transverse arcs rapidly responded within 15 min regardless of the strain magnitude to facilitate the subsequent changes in the orientation and elongation of the cytoplasm. The cyclic stretches induced the additional formation of perinuclear cap fibers and their increased number was almost maintained with a slight decline after 2-h-long stretch release. The slow formation and high stability of perinuclear cap fibers were linked to the slow reorientation kinetics and partial morphology recovery of nucleus in the presence or absence of cyclic stretches. The reorganization of stress fiber subtypes occurred in accordance with the reversible distribution of myosin II. These findings allowed us to propose a model for stretch-induced responses of the cytoplasm and nucleus in epithelial cells based on different mechanoadaptive properties of stress fiber subtypes.

Scale-Up Evaluation of a Composite Tumor Marker Assay for the Early Detection of Renal Cell Carcinoma.

The early detection of renal cell carcinoma (RCC) using tumor markers remains an attractive prospect for the potential to downstage the disease. To validate the scale-up clinical performance of potential tumor markers for RCC (as a single marker and as a composite tumor marker composed of nicotinamide N-methyltransferase (NNMT), L-Plastin (LCP1), and non-metastatic cells 1 protein (NM23A)), the scale-up assay was performed. Patients with RCC from multiple domestic institutes were included in the clinical evaluation for reassessment and improvement of the established triple markers of our product. For the diagnostic performance of the composite markers, the best-split cutoff points of each marker (147 pg/mL for NNMT, 1780 pg/mL for LCP1, and 520 pg/mL for NM23A) were installed. Serum levels of NNMT, LCP1, and NM23A were greatly increased in subjects with RCC (p < 0.0001). In 1042 blind sample tests with control individuals (n = 500) and patients with RCC (n = 542), the diagnostic sensitivity and specificity of the composite three-marker assay were 0.871 and 0.894, respectively, and the resulting AUC (Area under Curve) of ROC (Receiver Operating Characteristic) was 0.917. As a single marker, the diagnostic accuracies of NNMT, LCP1, and NM23A, as estimated by ROC, were 0.833, 0.844, and 0.601, respectively. The composite three-marker assay with NNMT, LCP1, and NM23A is a more improved novel serum marker assay for the early detection of RCC in cases of renal mass or unknown condition. The NNMT, LCP1, and NM23A triple marker assay could be a powerful diagnostic tumor marker assay to screen the early stage of RCC.

An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer.

Estrogen-related receptor gamma (ERRγ) is the NR3B subgroup of associated transcription factors. In this report, a new generation of a potent and selective ERRγ inverse agonist (25) with good biocompatibility was proposed. We also explored the potential of the newly developed compound 25 in the PDTC model to expand the original indications from ATC. In addition, an X-ray crystallographic study of the ligand and ERRγ co-complex showed that 25 completely binds to the target protein (PDB 6KNR). Its medicinal chemistry, including a distinctive structural study to in vivo results, denotes that 25 may be directed towards the development of a pivotal treatment for ERRγ-related cancers.

Development of a deformable lung phantom with 3D-printed flexible airways.

PURPOSE: Deformable lung phantoms have been proposed to investigate four-dimensional (4D) imaging and radiotherapy delivery techniques. However, most phantoms mimic only the lung and tumor without pulmonary airways. The purpose of this study was to develop a reproducible, deformable lung phantom with three-dimensional (3D)-printed airways. METHODS: The phantom consists of: (a) 3D-printed flexible airways, (b) flexible polyurethane foam infused with iodinated contrast agents, and (c) a motion platform. The airways were simulated using publicly available breath-hold computed tomography (CT) image datasets of a human lung through airway segmentation, computer-aided design modeling, and 3D printing with a rubber-like material. The lung was simulated by pouring liquid expanding foam into a mold with the 3D-printed airways attached. Iodinated contrast agents were infused into the lung phantom to emulate the density of the human lung. The lung/airways phantom was integrated into our previously developed motion platform, which allows for compression and decompression of the phantom in the superior-inferior direction. We quantified the reproducibility of the density (lung), motion/deformation (lung and airways), and position (airways) using breath-hold CT scans (with the phantom compressed and decompressed) repeated every two weeks over a 2-month period as well as 4D CT scans (with the phantom continuously compressed and decompressed) repeated twice over four weeks. The density reproducibility was quantified with a difference image (created by subtracting the rigidly registered baseline and the repeated images) in each of the compressed and decompressed states. Reproducibility of the motion/deformation was evaluated by comparing the baseline displacement vector fields (DVFs) derived from deformable image registration (DIR) between the compressed and decompressed phantom CT images with those of repeated scans and calculating the difference in the displacement vectors. Reproducibility of the airway position was quantified based on DIR between the baseline and repeated images. RESULTS: For the breath-hold CT scans, the mean difference in lung density between baseline and week 8 was -1.3 (standard deviation 33.5) Hounsfield unit (HU) in the compressed state and 0.4 (36.8) HU in the decompressed state, while large local differences were observed around the high-contrast structures (caused by small misalignments). By visual inspection, the DVFs (between the compressed and decompressed states) at baseline and last time point (week 8 for the breath-hold CT scans) demonstrated a similar pattern. The mean lengths of displacement vector differences between baseline and week 8 were 0.5 (0.4) mm for the lung and 0.3 (0.2) mm for the airways. The mean airway displacements between baseline and week 8 were 0.6 (0.5) mm in the compressed state and 0.6 (0.4) mm in the decompressed state. We also observed similar results for the 4D CT scans (week 0 vs week 4) as well as for the breath-hold CT scans at other time points (week 0 vs weeks 2, 4, and 6). CONCLUSIONS: We have developed a deformable lung phantom with 3D-printed airways based on a human lung CT image. Our findings indicate reproducible density, motion/deformation, and position. This phantom is based on widely available materials and technology, which represents advantages over other deformable phantoms.

Medical fluorophore 1 (MF1), a benzoquinolizinium-based fluorescent dye, as an inflammation imaging agent.

Structure-based targeting of fluorescent dyes is essential for their use as imaging agents for disease diagnosis. Here, we describe the development of the benzoquinolizinium compound Medical fluorophore 1 (MF1) as a novel biomedical imaging agent that allows the visualization of inflammation by virtue of its unique chemical structure. Lipopolysaccharide treatment stimulated the uptake of MF1 by bone marrow-derived macrophages, with no adverse effects on cell proliferation. In vivo fluorescence lifetime imaging revealed the accumulation of MF1 in carrageenan-induced acute inflammatory lesions in mice, which peaked at 6 h. MF1-based imaging also allowed monitoring of the response to the anti-inflammatory drugs dexamethasone and sulfasalazine. Thus, MF1 can be used to diagnose diseases characterized by inflammation as well as treatment efficacy.

Discovery of Potent, Selective, and Orally Bioavailable Estrogen-Related Receptor-γ Inverse Agonists To Restore the Sodium Iodide Symporter Function in Anaplastic Thyroid Cancer.

An inverse agonist of estrogen-related receptor-γ (ERRγ), an orphan nuclear receptor encoded by E srrg, enhances sodium iodide symporter-mediated radioiodine uptake in anaplastic thyroid cancer (ATC) cells, thereby facilitating responsiveness to radioiodine therapy in vitro. We synthesized potent, selective, and orally bioavailable ERRγ-inverse agonists and evaluated their activity by analyzing in vitro pharmacology and absorption, distribution, metabolism, excretion, and toxicity profiles. X-ray crystallographic analysis of the ligand and ERRγ complex showed that 35 completely binds to the target protein (PDB 6A6K ). Our results showed improved radioiodine avidity in ATC cells through compound 35-mediated upregulation of iodide-handling genes, leading to enhanced responsiveness to radioiodine therapy in vitro. Importantly, in vivo 124I-positron emission tomography/computed tomography imaging revealed that 35 increases radioiodine avidity in CAL62 tumors. Collectively, these results demonstrated that 35 can be developed as a promising treatment for ERRγ-related cancer in the future.

HSP27, ALDH6A1 and Prohibitin Act as a Trio-biomarker to Predict Survival in Late Metastatic Prostate Cancer.

BACKGROUND/AIM: The aim of this study was to evaluate the usefulness of biomarkers related to prostate cancer metastasis and survival of patients. MATERIALS AND METHODS: Proteomics were used for detecting significant differences in protein expression among normal prostate, localized prostate cancer and metastatic cancer using 2-dimensional gel electrophoresis and mass spectrometry. mRNA expression was then examined in order to further confirm significant differences in protein expression. A total of 7 proteins were found to be differentially expressed. Immunochemistry (IHC), was also used to confirm the levels of expression of the 7 proteins in prostate cancer. Survival analysis using the candidate markers was finally performed in 98 metastatic prostate cancer patients according to IHC results. RESULTS: In metastatic lesions, proteomic analysis indicated that heat shock protein (HSP) 27, prohibitin, glutathione S-transferase 1, fibrinogen ß chain, and aldehyde dehydrogenase 6A1 were up-regulated, while α1 antitrypsin, and HSP 60 were down-regulated. IHC revealed that HSP 27, ALDH6A1 and prohibitin were highly specific to metastatic tumor cells. HSP27 and prohibitin appeared more strongly in the incipient stage of cancer than metastatic cancer, and ALDH6A1 was significantly reduced in metastatic cancer (p<0.01). Of all proteins, phohibitin had the highest value in predicting survival. However, all three proteins were a stronger marker than each one separately. CONCLUSION: Trio-biomarker composed of HSP27, ALDH6A1 and prohibitin may predict survival of metastatic prostate cancer patients.

Effect of statins on experimental postoperative adhesion: a systematic review and meta-analysis.

Adhesion is a significant concern after surgery. Many researchers studied the anti-adhesive effect of statin, of which results were inconsistent. Thus, we purposed to perform a systematic review and meta-analysis to evaluate the effect of statins on postoperative adhesion in an experimental study. A comprehensive search was conducted using MEDLINE, EMBASE, and Google Scholar to identify animal studies that investigated the postoperative anti-adhesive effect of statins applied at the surgical area. Primary outcome measure was gross adhesion score. Secondary outcomes included microscopic adhesion score and tissue plasminogen activator (t-PA) activity. Totally, 298 rats from 9 animal studies (172 rats received statin therapy and 126 rats received placebo or no treatment) were included in the final analysis. The combined results showed that gross and microscopic adhesion scores were significantly lower in the statin group in comparison to the control group (standardized mean difference [SMD] = 1.65, 95% confidence interval [CI]: 1.02 to 2.28, Pchi2 < 0.001, I2 = 77.9%; SMD = 1.90, 95% CI: 1.10 to 2.79, Pchi2 < 0.001, I2 = 84.5%, respectively). However, there was no evidence of a difference in t-PA activity (SMD = -3.43, 95% CI: -7.95 to 1.09, Pchi2 < 0.001, I2 = 95.5%). In conclusion, statins were effective in preventing postoperative adhesion, as assessed based on gross and microscopic adhesion scores in rats.