Efficacy and safety of low profile stents in Y-stent assisted coil embolization of wide-necked bifurcation aneurysms: a systematic review and meta-analysis.

Low-profile stents may provide significant advantages in Y-stent-assisted coiling due to their miniaturized design and capability to be delivered through a 0.0165-inch microcatheter. We aim to investigate the safety and efficacy of using these newer versions of stents in Y-stent-assisted coiling for the treatment of wide-necked bifurcation aneurysms. We conducted a systematic review of the PubMed, Embase, Cochrane Library, and Web of Science databases up to September 2023, following the PRISMA guidelines. Eligible studies included ≥ 5 patients with intracranial wide-necked bifurcation aneurysms treated with Y-stent-assisted coiling using low-profile stents, providing angiographic and clinical outcomes. Two authors independently handled the search and selection. Primary outcomes were immediate and follow-up aneurysm occlusion, procedure-related complications, aneurysm recanalization, and retreatment. Secondary outcomes included technical success, procedure-related morbidity, procedure-related mortality, procedure-related stroke, and in-stent stenosis at follow-up. We analyzed the data using random-effects meta-analysis. In total, 19 studies including 507 patients with 509 aneurysms were included. 95% of the treated aneurysms were managed using the crossing Y-configuration. Technical success rate was 99%. Immediate adequate aneurysm occlusion was 90%. Follow-up angiographies were available for 443 aneurysms. The mean angiographic follow-up duration was 15.6 ± 1.9 months. The rates for follow-up adequate aneurysm occlusion and complete occlusion were 98% and 89%, respectively. After a mean clinical follow-up of 15 ± 2.4 months, a good clinical outcome was observed in 98% of patients. Overall, procedure-related morbidity and mortality rates were 1.3%, and 0.4%, respectively. Low-profile stents in Y-stent-assisted coiling outperform previous stent versions in terms of safety, efficacy, and technical success rates.

Multivariate analysis and GIS approaches for modeling and mapping soil quality and land suitability in arid zones.

Assessing soil quality marks the initial step in precision farming and agricultural management. Developing countries like Egypt face numerous hurdles in ensuring food security due to increasing populations and limited agricultural resources. A geographic information system (GIS) and multivariate analysis were utilized in the current work to evaluate and map a soil quality index (SQI). Moreover, the land suitability of the land for two plantations of the tree's oak (Quercus robur), and pine (Pinus silvestris), respectively was assessed using a parametric approach. A total of 82 soil profiles were selected to fulfill the objectives of the study. Based on the samples' PC scores, and agglomerative hierarchical clustering (AHC, the data was divided into two clusters: Cluster I and Cluster II, which collectively account for approximately 57% and 43% of the total data, respectively.. . The findings indicated that land suitability for planting Q. robur planted identified 2.14% of the research area as highly suitable (S1), 37.98% as moderately suitable (S2), and 59.89% as not suitable (N). Furthermore, the assessment of suitability for P. silvestris indicated that 50.88% of the investigated area was classified into: S1, 48.73% as S2, and 0.39% as N, which means it is not suitable for conservation activities. The research identified that soil depth beside excessive salinity and calcium carbonate as the primary soil constraints in the area in both clusters. The average soil depth, ECd and CaCO3 were 113.62 ± 12.41, 17.27 ± 10.23, 16.83 ± 6.57 in Cluster 1 and 45.43 ± 15.21, 22.42 ± 12.43, 21.55 ± 5.63 in Cluster II. The study demonstrates that integrating multivariate analysis with GIS enables a precise and streamlined assessment of the Soil Quality Index (SQI). Soil suitability modelling underscores the importance of implementing efficient management practices to attain agricultural sustainability in arid regions, particularly amidst intensive land utilization pressures.

Fiberbots: Robotic fibers for high-precision minimally invasive surgery.

Precise manipulation of flexible surgical tools is crucial in minimally invasive surgical procedures, necessitating a miniature and flexible robotic probe that can precisely direct the surgical instruments. In this work, we developed a polymer-based robotic fiber with a thermal actuation mechanism by local heating along the sides of a single fiber. The fiber robot was fabricated by highly scalable fiber drawing technology using common low-cost materials. This low-profile (below 2 millimeters in diameter) robotic fiber exhibits remarkable motion precision (below 50 micrometers) and repeatability. We developed control algorithms coupling the robot with endoscopic instruments, demonstrating high-resolution in situ molecular and morphological tissue mapping. We assess its practicality and safety during in vivo laparoscopic surgery on a porcine model. High-precision motion of the fiber robot delivered endoscopically facilitates the effective use of cellular-level intraoperative tissue identification and ablation technologies, potentially enabling precise removal of cancer in challenging surgical sites.

Green UPLC method for estimation of ciprofloxacin, diclofenac sodium, and ibuprofen with application to pharmacokinetic study of human samples.

Investigation of a unique and fast method for the determination and separation of a mixture of three drugs viz., ciprofloxacin (CIP), Ibuprofen (IBU), and diclofenac sodium (DIC) in actual samples of human plasma. Also, the technique was used to look at their pharmacokinetics study. Hydrocortisone was chosen as the internal standard (IS). The drugs were chromatographically separated using an Acquity ultra-performance liquid chromatography UPLC ® BEH C18 1.7 µm (2.1 × 150 mm) column with a mobile phase composed of acetonitrile: water (65:35, v/v) adjusted to pH 3 with diluted acetic acid. Plasma proteins were precipitated with acetonitrile. The separated drugs ranged from 0.3 to 10, 0.2-11, and 1-25 µg/mL for CIP, IBU, and DIC, respectively. Calibration curves were discovered to achieve linearity with acceptable correlation coefficients (0.99%). Examination of quality assurance samples showed exceptional precision and accuracy. Following the successful application of this improved technique to plasma samples, the pharmacokinetic characteristics of each selected drug were evaluated using (UPLC) with UV detection at 210 nm. Two green metrics were applied, the Analytical Eco-scale and the Analytical GREEnness Calculator (AGREE). Separation was achieved in only 4-min analysis time. The method's validation agreed with the requirements of the FDA, and the results were sufficient.

Potential health risk assessment for heavy metals in Tilapia fish of different spatiotemporal monitoring patterns in Kafr El-Shaikh and El-Faiyum Governorates of Egypt.

Heavy metal (HMs) levels were evaluated in aquacultured tilapia fish collected from two highly producing districts in Egypt (Kafr El-Sheikh and El-Faiyum Governorates) during two seasons (autumn 2021 and spring 2022). As well, health risk assessment of exposure to HMs in tilapia fish was studied. The results revealed that six HMs: As, Cu, Fe, Mn, Cr and Zn were predominant in fish samples of the first season (autumn 2021), while most of HMs were existed in samples of the second season. All samples of the two seasons were free of Hg. Notably, autumn season's fish samples showed higher concentrations of HMs than those of the spring season. As well, Kafr El-Sheikh farms were highly contaminated with HMs than those of El-Faiyum governorate. Risk assessment results indicated that the THQ values of As substantially exceeded 1 either for Kafr El-Shaikh samples (3.15 ± 0.5) or for El-Faiyum samples (2.39 ± 0.8) of autumn season. Meanwhile, THQ values for all HMs, in spring season 2021, were less than one whole. These results indicated a potential health risk arising from the exposure to HMs, As in particular, in fish samples of autumn season as compared to those of spring season. Therefore, there is a need for remedial applications, in such polluted aquacultures in autumn season, which are currently under investigation as an integral part of the research project that funded the current study.

In-Vivo Validation of a Novel Robotic Platform for Endovascular Intervention.

OBJECTIVE: In-vivo validation on animal setting of a pneumatically propelled robot for endovascular intervention, to determine safety and clinical advantage of robotic cannulations compared to manual operation. METHODS: Robotic assistance and image-guided intervention are increasingly used for improving endovascular procedures with enhanced navigation dexterity and accuracy. However, most platforms developed in the past decade still present inherent limitations in terms of altered clinical workflow, counterintuitive human-robot interaction, and a lack of versatility. We have created a versatile, highly integrated platform for robot-assisted endovascular intervention aimed at addressing such limitations, and here we demonstrate its clinical usability through in-vivo animal trials. A detailed in-vivo study on four porcine models conducted with our robotic platform is reported, involving cannulation and balloon angioplasty of five target arteries. RESULTS: The trials showed a 100% success rate, and post-mortem histopathological assessment demonstrated a reduction in the incidence and severity of vessel trauma with robotic navigation versus manual manipulation. CONCLUSION: In-vivo experiments demonstrated that the applicability of our robotic system within the context of this study was well tolerated, with good feasibility, and low risk profile. Comparable results were observed with robotics and manual cannulation, with clinical outcome potentially in favor of robotics. SIGNIFICANCE: This study showed that the proposed robotic platform can potentially improve the execution of endovascular procedures, paving the way for clinical translation.

Mass flow and consumption calculations of pharmaceuticals in sewage treatment plant with emphasis on the fate and risk quotient assessment.

In Egypt, pharmaceuticals consumption increased dramatically owing to the population growth and the unrestricted sale manner. Accordingly, the occurrence and fate of nine common pharmaceutical active compounds (PhACs) were scrutinized at a sewage treatment plant (STP) in Giza, Egypt. The levels of these PhACs were assessed in different the wastewater treatment stages and dewatered sludge phase using high-performance liquid chromatography coupled with photodiode arrays detector. The average concentrations of the total PhACs detected in influent, primary sedimentation effluent (PSE) and final effluent (FE) were 227, 155 and 89 µg L-1, respectively. The overall removal efficiency of the individual PhACs ranged from 18 to 72% removal. The occurrence trend revealed that biodegradation and adsorption are the concurrently removal mechanisms of the studied PhACs. The overall consumption per day in West of Greater Cairo was estimated based on influent concentration of STP. Sulfamethoxazole, paracetamol and diclofenac were detected with the highest levels in the influent of STP, PSE and FE as well as in the dewatered sludge. Furthermore, the high concentrations of these compounds in the sludge confirm the adsorption pathway removal of theses PhACs. The risk quotient (RQ) assessment for the detected PhACs in FE is greatly higher than the predicted non-effect concentration (PNEC). Conclusively, the FE of STP is considered a risky source for PhACs in adjacent surface water.

Current State of Robotics in Interventional Radiology.

As a relatively new specialty with a minimally invasive nature, the field of interventional radiology is rapidly growing. Although the application of robotic systems in this field shows great promise, such as with increased precision, accuracy, and safety, as well as reduced radiation dose and potential for teleoperated procedures, the progression of these technologies has been slow. This is partly due to the complex equipment with complicated setup procedures, the disruption to theatre flow, the high costs, as well as some device limitations, such as lack of haptic feedback. To further assess these robotic technologies, more evidence of their performance and cost-effectiveness is needed before their widespread adoption within the field. In this review, we summarise the current progress of robotic systems that have been investigated for use in vascular and non-vascular interventions.

Highly Integrated Multi-Material Fibers for Soft Robotics.

Soft robots are envisioned as the next generation of safe biomedical devices in minimally invasive procedures. Yet, the difficulty of processing soft materials currently limits the size, aspect-ratio, manufacturing throughput, as well as, the design complexity and hence capabilities of soft robots. Multi-material thermal drawing is introduced as a material and processing platform to create soft robotic fibers imparted with multiple actuations and sensing modalities. Several thermoplastic and elastomeric material options for the fibers are presented, which all exhibit the rheological processing attributes for thermal drawing but varying mechanical properties, resulting in adaptable actuation performance. Moreover, numerous different fiber designs with intricate internal architectures, outer diameters of 700 µm, aspect ratios of 103 , and a fabrication at a scale of 10s of meters of length are demonstrated. A modular tendon-driven mechanism enables 3-dimensional (3D) motion, and embedded optical guides, electrical wires, and microfluidic channels give rise to multifunctionality. The fibers can perceive and autonomously adapt to their environments, as well as, probe electrical properties, and deliver fluids and mechanical tools to spatially distributed targets.

A case study of a real-time internet of things system for site-specific potato crop management in El-Salhia Area-Egypt.

The site-specific management is the technology that considers the natural variability within the same field of factors related to crop growth to improve its management practices such that the agricultural treatments are varied for field's small production zones saving resources and environment, and improving crop quality and size. Since site-specific decisions are not far from the Fourth Industrial Revolution and the concept of processes automation, this work addresses improving the process of spatial variability analysis and thus supporting management decisions by developing a system-entitled EGYPADS-based on the Internet of Things and its enabling technologies. EGYPADS automates data collection, zones delineation according to their land suitability evaluation, and maps generation. The paper addresses a case study of potato crop in a specific area in Egypt, El-Salhia, in which eighty-five sites were chosen as main dataset for the modeling process during different stages of crop growth. Three management zones were recognized of the selected field based on the differentiation in their land suitability characteristics, representing about 5%, 65%, and 30% of the total area, respectively. The structure, screens, and services of EGYPADS are described in this paper. EGYPADS offered services include: management zones delineation using absolute and virtual coordinates, Land Suitability Assessment (LSA), data entry from field in real-time as well as from excel sheets, saving maps in suitable format for variable rate application, real-time and historical data processing, centralized management, and flexible formulation of events and related actions. The implementation of EGYPADS was verified. The system dynamically produces non-contiguous isobands, each representing a specific range of parameter values, and can be properly exported for use by other programs or smart machinery. It was proven that EGYPADS supports more than one land with different geometry, area, location, and number of nodes. EGYPADS was compared with the traditional LSA method, and was found to produce similar management zones.

A novel gallium oxide nanoparticles-based sensor for the simultaneous electrochemical detection of Pb2+, Cd2+ and Hg2+ ions in real water samples.

Differential pulse voltammetry (DPV) using gallium oxide nanoparticles/carbon paste electrode (Ga2O3/CPE) was utilized for the simultaneous detection of Pb2+, Cd2+ and Hg2+ ions. Ga2O3NPs were chemically synthesized and fully characterized by Fourier-transform infrared (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Through the assay optimization, electrochemical screening of different nanomaterials was carried out using the cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) in order to determine the best electrode modifier that will be implemented for the present assay. Consequently, various parameters such as electrode matrix composition, electrolyte, deposition potential, and deposition time were optimized and discussed. Accordingly, the newly developed sensing platform showed a wide dynamic linear range of 0.3-80 µM with detection limits (LODs) of 84, 88 and 130 nM for Pb2+, Cd2+ and Hg2+ ions, respectively. While the corresponding limit of quantification (LOQ) values were 280, 320 and 450 nM. Sensors selectivity was investigated towards different non-targeting metal ions, whereas no obvious cross-reactivity was obtained. Eventually, applications on real samples were performed, while excellent recoveries for the multiple metal ions were successfully achieved.

Biomarker Expression Profiling in Cervix Carcinoma Biopsies Unravels WT1 as a Target of Artesunate.

BACKGROUND/AIM: Artemisinin and its derivatives are not only approved antimalarial drugs but also exert strong anticancer activity. Based on the clinical activity of artesunate (ART) that has been previously reported in cervix carcinoma, we investigated a panel of 12 different biomarkers and identified the Wilms Tumor 1 (WT1) protein as a potential target of ART. PATIENTS AND METHODS: Matched biopsies of cervical carcinoma before, during, and after therapy from patients treated with ART were investigated for induction of apoptosis (TUNEL assay) and expression of Wilms Tumor protein 1 (WT1), 14-3-3 ζ, cluster of differentiation markers (CD4, CD8, CD56), ATP-binding cassette transporter B5 (ABCB5), glutathione S-transferase P1 (GSTP1), inducible nitric oxide synthase (iNOS), translationally controlled tumor protein (TCTP), eukaryotic elongation factor 3 (eIF3), and ADP/ATP translocase by immunohistochemistry. WT1 has been selected for more detailed analyses using molecular docking in silico, microscale thermophoresis using recombinant WT1, and cytotoxicity testing (resazurin assay) using HEK293 cells transfected with four different WT1 splice variants. RESULTS: The fraction of apoptotic cells and the expression of WT1, 14-3-3 ζ, and CD4 increased upon ART treatment in tumors of patients. ART was bound in silico to a domain located at the DNA-binding site of WT1, while dihydroartemisinin (DHA) was bound with low affinity to a different site of WT1 not related to DNA-binding. The results were verified using microscale thermophoresis, where ART but not DHA bound to recombinant WT1. Transfectants overexpressing different WT1 splice variants exerted low but significant resistance to ART (≈2-fold). CONCLUSION: WT1 may represent a novel target of ART in cancer cells that contribute to the response of tumor cells to this drug.

A Multicenter, Single-Blind, Case-Control, Immunohistochemical Study of Orbital Tissue in Thyroid Eye Disease.

Background: Thyroid eye disease (TED) involves several pathogenic pathways and a battery of infiltrating mononuclear cells, cytokines, and chemokines in the orbit. Revealing the main molecules, which play a major role in the pathogenesis of TED, will help developing novel treatment strategies. Methods: In a multicenter, single-blind, case-control study, 60 tissue samples were collected during orbital decompression (44 TED patients) or non-TED related oculoplastic (16 controls) surgeries. Formalin-fixation and paraffin embedding preserved orbital tissue. Tissue sections were immunostained with 18 antibodies by the micro-polymer labeling technique. Immunostaining slides were scanned by Panoramic Desk and blindly evaluated by a user-independent viewer software. Results: Marked lymphocyte infiltration was observed in orbital tissue specimens of patients with clinically active TED (n = 22) and to a much lesser extent in inactive cases (n = 22), while it was absent in controls. Increased vascularity was noted in all samples, with orbital congestion in specimens of clinically active TED. Tissue fibrosis was present in TED samples but not in controls. Immunohistochemistry of orbital tissue clearly differentiated between TED and controls, as well as between active and inactive TED. In contrast to controls and with the exception of cluster of differentiation 20 (CD20), 17 out of 18 antibodies were highly expressed in orbital connective tissue of TED patients. Especially, thyrotropin receptor (TSH-R), insulin-like growth factor 1 receptor (IGF-1R), CD40, cluster of differentiation 40 ligand (CD40L), CD3, CD68, interleukin-17A (IL-17A), IL-23A, IL-1ß, IL-4, regulated on activation, normal T cell expressed and secreted (RANTES), macrophage chemoattractant protein 1 (MCP-1), IL-16, and B cell activating factor (BAFF) were overexpressed in clinically active TED (all p < 0.001). Also, the expression of CD40L, IL-17A, IL-23A, IL-6, IL-1ß, RANTES, and BAFF was very high (TED/control ratio >3), moderate (ratio >2), and low in active (p < 0.001), inactive TED and controls, respectively. The expression of TSH-R, IGF-1R, CD40, CD40L, CD3, CD68, CD20, IL-17A, IL-23A, RANTES, MCP-1, and BAFF positively and significantly correlated with both serum TSH-R stimulatory antibody concentrations and clinical activity scores while it negatively correlated with TED duration. Orbital irradiation decreased TSH-R (p < 0.001) and IGF-1R expression (p = 0.012); in contrast, neither smoking, age, nor gender did impact immunohistochemical staining. Conclusions: Adaptive and cell-mediated immunity, overexpression of TSH-R/IGF-1R and CD40/CD40L are the relevant pathomechanisms in TED. Targeting these key players in the active phase of the disease offers specific and novel treatment approaches.

Disruption of Lipid Raft Microdomains, Regulation of CD38, TP53, and MYC Signaling, and Induction of Apoptosis by Lomitapide in Multiple Myeloma Cells.

BACKGROUND/AIM: Multiple myeloma (MM) is characterized by accumulation of a malignant clone of plasma cells in the bone marrow. Curative treatments are not yet available. Therefore, we undertook a drug repurposing approach to identify possible candidates from a chemical library of 1,230 FDA-approved drugs by virtual drug screening. As a target, we have chosen the non-receptor Bruton's tyrosine kinase (BTK) which is one of the main regulators of the MM biomarker CD38. MATERIALS AND METHODS: In silico virtual screening was performed by using PyRx. Flow cytometry was applied for cell cycle and apoptosis analysis. Furthermore, protein and gene expression was determined by western blotting and microarray hybridization. Lipid raft staining was observed by confocal microscopy. RESULTS: The in silico identified lipid-lowering lomitapide presented with the strongest cytotoxicity among the top 10 drug candidates. This drug arrested the cell cycle in the G2/M phase and induced apoptosis in MM cells. Western blot analyses revealed that treatment with lomitapide induced cleavage of the apoptosis regulator PARP and reduced the expression of CD38, an integral part of lipid rafts. Using confocal microscopy, we further observed that lipid raft microdomain formation in MM cells was inhibited by lomitapide. In four MM cell lines (KMS-12-BM, NCI-H929, RPMI-8226, and MOLP-8) treated with lomitapide, microarray analyses showed not only that the expression of CD38 and BTK was down-regulated, but also that the tumor suppressor gene TP53 and the oncogene c-MYC were among the top deregulated genes. Further analysis of these data by Ingenuity pathway analysis (IPA) suggested that lomitapide interferes with the cross-talk of CD38 and BTK and apoptosis-regulating genes via TP53 and c-MYC. CONCLUSION: Lomitapide treatment led to disruption of lipid raft domains and induction of pro-apoptotic factors and might, therefore, be considered as a potential therapeutic agent in MM.

Artemisinin derivative FO-ARS-123 as a novel VEGFR2 inhibitor suppresses angiogenesis, cell migration, and invasion.

Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has been considered an important strategy for cancer therapy. VEGFR2 inhibitors targeting tumor angiogenic pathways have been widely used in clinical cancer treatment. However, inherent or acquired resistance to anti-angiogenic drugs may occur and thus limit their clinical application. New VEGFR2 inhibitors are still highly demanded. The aim of this study was to investigate VEGFR2-targeted artemisinin (ARS)-type compounds for cancer treatment. Here, we reported the ARS derivative FO-ARS-123 as a novel VEGFR2 inhibitor, which displayed potent binding activity with VEGFR2 in in silico by molecular docking (pKi, 0.40 ± 0.31 nM) and in vitro by microscale thermophoresis (Kd, 1.325 ± 0.055 µM). In addition, compound FO-ARS-123 displayed a strong inhibition on cell proliferation of a broad range of cancer cells as well as suppressed cell migration and invasion. Remarkably, FO-ARS-123 exerted profound anti-angiogenesis effects in the in vitro tube formation assay and in vivo CAM assay. These results suggest that FO-ARS-123 might be a novel and promising anti-angiogenesis agent for cancer treatment.

Biomarker Profiling Revealed Carcinoembryonic Antigen as a Target of Artesunate in a Ductal Breast Cancer Patient.

BACKGROUND/AIM: Patients with metastatic tumors commonly have a poor prognosis. Frequently, patients suffering from progressive tumors have a high willingness for the compassionate use of non-approved medications. One of these medications is the antimalarial drug artesunate (ART) which also showed profound anticancer activity in vitro, in vivo, and in preliminary clinical pilot studies. Herein, we report on the compassionate use of ART in a patient with metastatic breast cancer. PATIENTS AND METHODS: The clinical course of a Caucasian female who was diagnosed with ductal breast cancer at the age of 33 is described. Tumor markers in the blood have been measured, and tumor-associated protein expression has been determined by immunohistochemistry. Microscale thermophoresis and molecular docking in silico were used to study protein-drug interactions. RESULTS: The tumor responded to ART administered at doses of 150-300 mg daily, and the patient experienced a stabilization of her disease for 1.5 years. ART treatment caused no or minimal side-effects (headache, dizziness, slight tachycardia, slight stomach upset, slight fatigue). Tumor marker determination in the blood of the patient revealed a reduction of carcinoembryonic antigen (CEA), but not CA 27.29 or CA 15.3 levels. We hypothesized that the reduction of CEA levels might be due to binding of ART to this protein. Microscale thermophoresis with recombinant CEA indeed showed binding of ART to this protein in vitro. This result was verified by molecular docking in silico. Immunohistochemical biomarker profiling and computerbased quantification of biomarker expression in a tumor biopsy revealed strong expression of COX2, GRP78, CD71, GSTP1, and c-MYC but weak or minimal expression of VEGFR, P-glycoprotein, survivin, and LOX1. CONCLUSION: Among a panel of tumor-related proteins tested, the interaction with CEA may have contributed to the anticancer activity of ART in this patient. It deserves further investigation whether CEA represents not only a valuable biomarker but also a treatment target. ART might be useful for the individualized treatment of metastatic breast tumors.

Protein Expression Profiling and Virtual Drug Screening as an Approach for Individualized Therapy of Small Cell Vaginal Carcinoma.

BACKGROUND: Small cell vaginal carcinoma is a very rare gynecological cancer and treatments including chemo- and radiotherapy have had limited success. CASE REPORT: We report the case of a 37-year-old female, where intensive treatment with the combination of paclitaxel, carboplatin, irinotecan, and camptothecin with and without irradiation did not avoid metastasis of the tumor and the death of the patient. In an attempt to develop a strategy for individualized tumor therapy, we performed immunohistochemistry of 19 cancer-related proteins using a biopsy sample. Strong expression was observed for glutathione S-transferase P1 (GSTP1), epidermal growth factor receptor (EGFR), inducible nitric oxide synthetase (iNOS), nuclear factor kappa B (NF-κB), the oncogene c-MYC, vascular endothelial growth factor (VEGF), and the proliferation marker Ki-67. Intermediate expression was found for the oncogene SRC, ß-catenin, and the viral E7 protein. We then performed virtual drug screening with PyRx and molecular docking with AutoDock 4.2.6 by using the three-dimensional structures of these proteins and a chemical library of 1,577 FDA-approved drugs, in a drug repurposing approach. The top 15 compounds were either approved anticancer drugs or drugs used to treat non-malignant diseases. These compounds were bound with comparable or even higher affinity to the targets compared to control inhibitors. Several of these compounds were bound with high affinity to more than one of these target proteins, further supporting the drug repurposing concept. CONCLUSION: These drugs might offer additional opportunities to reach treatment responses. This approach of individualized tumor therapy might be theoretically not only applicable for small cell vaginal carcinoma but for other tumor entities as well.

Expression of the Stem Cell Marker ABCB5 in Normal and Tumor Tissues.

BACKGROUND/AIM: The ATP-binding cassette subfamily B member 5 (ABCB5) transporter plays a pivotal role in melanocyte progenitor cell fusion and has been identified as a tumor-initiating cell marker. In this study, we determined ABCB5 expression in normal tissues among various species, i.e., Homo sapiens, Mus musculus (mouse), Rattus norvegicus (rat), Sus scrofa domesticus (pig), Gallus gallus (chicken), Anser anser (goose), Poecilia reticulata (Guppy fish), and Lumbricus terrestris (earthworm), as well as 426 biopsies of different human tumor types (colorectal, cervical, endometrium, vaginal, nasopharyngeal, kidney, breast, colon, prostate, pancreas, lung, gallbladder, bladder, brain, liver, skin, small intestine, testis, tonsil, uterus, thyroid, stomach, esophagus, fallopian, parotid, and ovary). MATERIALS AND METHODS: Using immunohistochemical staining, ABCB5 expression was detected and evaluated in formalin-fixed, paraffin-embedded sections. RESULTS: High ABCB5 expression was found in normal tissues in specialized cells with secretory and excretory functions, chorionic villi of the placenta, hepatocytes, and blood-tissue barrier sites in the brain and testis. Besides, heterogeneous expression of ABCB5 was also observed in many different tumor types derived from breast, endometrium, ovary, uterus, cervix, prostate, lung, brain, colon, liver, nasopharynx, and others. CONCLUSION: The localization of ABCB5 in different normal tissues suggests that this protein has an excretory pumping role for physiological metabolites and xenobiotics. This physiological role highlighted its possible impact on the development of multidrug resistance in tumors. Further studies are required to establish the possible clinical significance of ABCB5 as a predictive marker for drug resistance and as a prognostic marker for patient survival.