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Hany SM Ali,1,2 Ahmed F Hanafy,3 Rawan Bafail,1 Hamad Alrbyawi,1 Marey Almaghrabi,1 Yaser M Alahmadi,4 Samar El Achy5 1Department of Pharmaceutics and Pharmaceutical Industries, College of Pharmacy, Taibah University, Madinah, Al-Madinah Al-Munawwarah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt; 3Research and Development Department, Al Andalous Pharmaceutical Industries, Giza, Egypt; 4Department of Pharmacy Practice, College of Pharmacy, Taibah University, Madinah, Al-Madinah Al-Munawarah, 30001, Saudi Arabia; 5Department of Anatomical Pathology, Faculty of Medicine, University of Alexandria, Alexandria, EgyptCorrespondence: Hany SM Ali, Email hsali@taibahu.edu.sa, hafandy2000@yahoo.comBackground: Budesonide (BUD) is a BCS class II medication with poor water solubility and limited oral bioavailability. In this study, innovative solid self-microemulsifying drug delivery systems (BUD-SMEDDS) were developed for effective local management of distal ulcerative colitis (UC).Methods: Based on solubility and emulsification tests, the components of the self-microemulsifying drug delivery system (SMEDDS) were Capryol™ 90, Tween 80, and Transcutol HP. The impacts of BUD-SMEDDS ingredients (as inputs) on the average globule size (AGS), polydispersity index (PDI), and self-emulsification time (SET) as responses were investigated using the Box–Behnken design methodology. Solid rectal systems were then fabricated using the optimized values of SMEDDS components in Lutrol® bases. The developed systems were evaluated for in vitro characteristics and in vivo efficacy using a rat colitis model.Results: For all responses, the greatest impact was attributed to the oil content of SMEDDS. An optimized BUD-SMEDDS with AGS of 33 ± 2.9 nm, PDI of 0.29 ± 0.03 and SET of 25 ± 2.5 s) was selected for rectal formulations. The developed formulations demonstrated acceptable physical characteristics and mucoadhesive abilities. Differential scanning calorimetric (DSC) analysis revealed the absence of BUD crystallinity in the SMEDDS formulations. The drug release patterns could be regulated by selecting the grade and composition of the incorporated Lutrols. Clinical and histopathological assessments revealed considerable improvements in animals treated with BUD-SMEDDS formulations.Conclusion: Overall findings confirmed the superior capability of solid SMEDDS as BUD carriers to manage distal colitis in tested animals.Keywords: Budesonide, SMEDDS, Ulcerative colitis, Box Behnken design, efficacy

Hanaa Shafiek,1 Shaimaa Elbialy,1 Samar Nabil El Achy,2 Ahmed Youssef Shaaban Gad11Chest Diseases Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 2Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, EgyptCorrespondence: Hanaa ShafiekChest Diseases Department, Faculty of Medicine, Alexandria University, El-Khartoom Square, Alexandria 21526, EgyptTel +20 109 590 7320Email whitecoat_med@yahoo.comObjectives: We aimed to evaluate the efficacy, safety, and diagnostic utility of transbronchial cryobiopsy (TBCB) in diagnosing diffuse parenchymal lung diseases (DPLDs) in an Egyptian population and to identify common DPLD pathologies among them.Methods: This prospective interventional study enrolled 25 Egyptian patients presenting to the Main Alexandria University Hospital who had clinical and radiological features of DPLD, but insufficient elements to achieve definite features of usual interstitial pneumonia on chest high-resolution computed tomography. Twelve patients were subjected to TBCB and 13 to forceps transbronchial lung biopsy (TBLB).Results: The diagnostic yield was significantly higher among the TBCB group (83.3%), and increased to 100% with clinicopathological correlation vs the TBLB group (38.5%, P=0.041). Granulomatous diseases (24%, either sarcoidosis or hypersensitivity pneumonitis) were the commonest pathology, followed by malignancy (12%) in both groups. TBCB sizes were 2.5–5 mm vs 1-3 mm in TBLB (P

This study aimed at preparing sustained release rosuvastatin (Ru) calcium carbonate (CC) co-precipitate nano-formulation for local intra-osseous application in osteoporotic rats. Nano-formulations were prepared by the co-precipitation method using different concentrations of polyvinyl alcohol (PVA) (0.2, 0.4, 0.6 %) as a stabilizer and equimolar ratios of calcium chloride and calcium carbonate (0.1, 0.3 or 0.5 M). Pre-formulation examination including; FTIR and X-ray diffraction confirmed the formation of CC nanoparticles in a crystalline structure that was preserved before and after loading with Ru. The optimized formula showing; PS of 105.71 ± 5.10 nm, PDI of 0.25 ± 0.02, ZP of -44.70 ± 0.09 mV, % EE of 60.16 ± 1.58 and a quasi-spherical nanoparticle with nano-deposition of Ru crystals adsorbed on them as seen under TEM and SEM, was then integrated in 20 % Pluronic gel. The Ru-gel exhibited good rheological behavior with a short gelation time of 20 sec and a sustained release pattern of 30 % for the optimized Ru/CC gel versus ≈ 90 % for the Ru/CC dispersion after 6 h. In-vivo, ovariectomy-induced osteoporotic rats were used to cause a bone defect in the tibial metaphysis. The drill-hole defects were then filled with the formulations under test and examined 30 days postoperatively. Through SEM-EDX scanning, histological assessments, and evaluation of bone metabolic markers, Ru/CC treatment significantly enhanced bone healing, improved bone microarchitecture, increased trabecular bone area, enhanced osteogenic gene expression, and reduced osteoclast activity. Experiments proved that Ru/CC successfully enhances osteogenesis and reduces osteoclastogenesis, proposing it as a promising therapeutic approach for enhancing bone regeneration in osteoporosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Toxoplasmosis is a pervasive parasitic infection possessing a chief impact on both public health and veterinary medicine. Unfortunately, the commercially-available anti-Toxoplasma agents have either serious side effects or diminished efficiency, specifically on the Toxoplasma tissue cysts. In the present study, metformin (The first-line treatment for type 2 diabetes mellitus) was investigated for the first time against chronic cerebral toxoplasmosis in mice model experimentally-infected with ME49 strain versus spiramycin. Two metformin regimens were applied; starting one week before the infection and four weeks PI. Parasitological, ultrastructural, histopathological, immunohistochemical, immunological, and biochemical assessments were performed. The anti-parasitic effect of metformin was granted by the statistically-significant reduction in tissue-cyst burden in both treatment regimens. This was accompanied by markedly-mutilated ultrastructure and profound amelioration of the cerebral histopathology with remarkable decline in the brain CD4 + and CD8 + T cell count. Besides, diminution of anti-Toxoplasma IgG and brain GSH levels was evident. Ultimately, the present findings highlighted the powerful promising therapeutic role of metformin in the management of chronic toxoplasmosis on a basis of anti-parasitic, anti-inflammatory, and anti-oxidant possessions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Apparent diffusion coefficient (ADC) value is an important part of bladder cancer magnetic resonance imaging (MRI) assessment and can predict the aggressive and invasive potentials. There is growing interest in whole tumor volume measurements., Purpose: To investigate if the volumetric ADC measurement method will significantly exceed the diagnostic performance of the selected region of interest (ROI) method in everyday practice., Material and Methods: A prospective evaluation was carried out of 50 patients with bladder cancer by two radiologists. The mean and the minimum ADC values were measured using both methods. The inter-reader agreement was determined by the intraclass correlation coefficient. The ADC values were compared between different grades, states of muscle invasion, and lympho-vascular invasion (LVI); then, validity was evaluated using receiver operating characteristic (ROC) curves. Areas under the curve (AUC) were then compared for the level of statistical significance., Results: The inter-observer agreement was excellent for the ADC values using both methods. The volumetric measurement provides higher mean and lower minimum ADC values with statistically significant differences ( P <0.00001). The highest diagnostic accuracy for differentiating tumor grade and predicting muscle invasion was for the minimum ADC by a selected ROI. However, the differences between the achieved AUCs were of no statistical significance. None of the ADC values predicted LVI with statistical significance., Conclusion: The selected ROI and volumetric measurement methods of mean and minimum ADC in bladder cancer yield different values, still having comparable diagnostic performance with accurate ROI sampling. The minimum ADC value by ROI is preferred in everyday clinical practice., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pioglitazone (Actos) is one of the most recent oral antidiabetic drugs for treating the second type of diabetes mellitus as a common chronic and lifelong disease, but with harmful side effects. The objective of this study is to evaluate the effectiveness of Artemisia annua L. extract against the Actos drug side effects in the male albino mice. In present study, the use of Actos drug alone induced hepatotoxicity, renal inflammation, hematological disorders and bladder cancer, which are manifested by biochemical abnormalities and histopathological changes, moreover, the severity of toxicity depends on its dose. In contrast, the concurrent treatment with both Actos drug (45 mg/kg) and Artemisia extract (4 g/kg) was effective against the harmful side effects of the Actos drug. Where, the biochemical, hematological and histopathological investigations showed that the hepatotoxicity, renal inflammation, hematological disorders and histopathological changes were improved using combination of Actos and Artemisia extract. In addition, the results of TNF-ɑ oncogene expression levels in bladder tissues were significantly decreased by about 99.99% using the mix of both Actos drug and Artemisia extract. In conclusion, these findings reveal that the Artemisia annua extract on TNF-ɑ oncogene expression level is very significant and effective natural product against harmful side effects of pioglitazone which associated with an increased risk of incident bladder cancer among people, but for application more studies must be achieved in that field., (© 2023. The Author(s).)

Background: Mitoxantrone has proved efficacy in treatment of multiple sclerosis (MS). The fact that physical exercise could slow down the progression of disease and improve performance is still a debatable issue, hence; we aimed at studying whether combining mitoxantrone with exercise is of value in the management of MS., Methods: Thirty-six male rats were divided into sedentary and exercised groups. During a 14-day habituation period rats were subjected to exercise training on a rotarod (30 min/day) before Experimental Autoimmune Encephalomyelitis (EAE) induction and thereafter for 17 consecutive days. On day 13 after induction, EAE groups (exercised &sedentary) were divided into untreated and mitoxantrone treated ones. Disease development was evaluated by motor performance and EAE score. Cerebrospinal fluid (CSF) was used for biochemical analysis. Brain stem and cerebellum were examined histopathological and immunohistochemically., Results: Exercise training alone did not add a significant value to the studied parameters, except for reducing Foxp3 immunoreactivity in EAE group and caspase-3 in the mitoxantrone treated group. Unexpectedly, exercise worsened the mitoxantrone effect on EAE score, Bcl2 and Bax. Mitoxantrone alone decreased EAE/demyelination/inflammation scores, Foxp3 immunoreactivity, and interleukin-6, while increased the re-myelination marker BDNF without any change in tumor necrosis factor-α. It clearly interrupted the apoptotic pathway in brain stem, but worsened EAE mediated changes of the anti-apoptotic Bcl2 and pro-apoptotic marker Bax in the CSF., Conclusions: The neuroprotective effect of mitoxantrone was related with remyelination, immunosuppressive and anti-inflammatory potentials. Exercise training did not show added value to mitoxantrone, in contrast, it disrupts the apoptotic pathway., (© 2022. The Author(s).)

Aims: The fact that physical activity besides central cholinergic enhancement contributes in improving neuronal function and spastic plasticity, recommends the use of the anticholinesterase and cholinergic drug galantamine with/without exercise in the management of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS)., Materials and Methods: Sedentary and 14 days exercised male Sprague Dawley rats were subjected to EAE. Hereafter, exercised rats continued on rotarod for 30 min for 17 consecutive days. At the onset of symptoms (day 13), EAE sedentary/exercised groups were subdivided into untreated and post-treated with galantamine. The disease progression was assessed by EAE score, motor performance, and biochemically using cerebrospinal fluid (CSF). Cerebellum and brain stem samples were used for histopathology and immunohistochemistry analysis., Key Findings: Galantamine decreased EAE score of sedentary/exercised rats and enhanced their motor performance. Galantamine with/without exercise inhibited CSF levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6), and Bcl-2-associated X protein (Bax), besides caspase-3 and forkhead box P3 (Foxp3) expression in the brain stem. Contrariwise, it has elevated CSF levels of brain derived neurotrophic factor (BDNF) and B-cell lymphoma (Bcl-2) and enhanced remyelination of cerebral neurons. Noteworthy, exercise boosted the drug effect on Bcl-2 and Bax., Significance: The neuroprotective effect of galantamine against EAE was associated with anti-inflammatory and anti-apoptotic potentials, along with increasing BDNF and remyelination. It also normalized regulatory T-cells levels in the brain stem. The impact of the add-on of exercise was markedly manifested in reducing neuronal apoptosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose/objective: The objective of this study was to assess the association between pretreatment p53, hypoxia inducible factor 1a (HIF1a), Ki-67, carbonic anhydrase-9 (CA-9), and glucose transporter 1 (GLUT1) expression in locally advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), local-regional control (LC), and distant metastases-free survival (DMFS)., Patients and Methods: Twenty-eight patients treated definitively and consecutively for cervical cancer with CRT had p53, HIF1a, Ki-67, CA-9, and GLUT1 protein expression assessed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes. Outcomes were stratified by p53 (H-score: <15 vs. ≥15), HIF1a (H-score: <95 vs. ≥95), Ki-67 (labeling index <41% vs. ≥41%), CA-9 (H-score: <15 vs. ≥15), and GLUT1 (H-score: <175 vs. ≥175) expression. OS, PFS, LC, and DMFS rates were calculated using the Kaplan-Meier method, and differences between groups were evaluated by the log-rank test., Results: Notable clinical characteristics of the cohort included median age of 51 years (range: 32 to 74 y), FIGO stage IIB disease (57.2%), clinical node-negative disease (64.3%), squamous cell carcinoma (89.3%), and adenocarcinoma (10.7%). Treatment outcomes included 5-year OS (57.2%), PFS (48.1%), LC (72.1%), and DMFS (62.9%). For HIF1a H-score <95 and ≥95, the 5-year OS (52.0% and 68.4%, P=0.58), PFS (53.0% and 40.9%, P=0.75), LC (71.6% and 68.2%, P=0.92), and DMFS (59.7% and 52.0%, P=0.91) were not significantly different. For Ki-67 labeling index <41% and ≥41%, the 5-year OS (44.9% and 66.6%, P=0.35), PFS (38.9% and 55.4%, P=0.53), LC (57.7% and 85.7%, P=0.22), and DMFS (67.3% and 61.0%, P=0.94) were not significantly different. For CA-9 H-score <15 and ≥15, the 5-year OS (54.4% and 66.7%, P=0.39), PFS (57.3% and 40.0%, P=0.87), LC (70.0% and 70.0%, P=0.95), and DMFS (70.0% and 46.7%, P=0.94) were not significantly different. For GLUT1 H-score <175 and ≥175, the 5-year OS (43.6% and 43.6%, P=0.32), PFS (55.6% and 49.5%, P=0.72), LC (72.9% and 71.5%, P=0.97), and DMFS (62.5% and 59.6%, P=0.76) were not significantly different. For p53, H-score <15 and ≥15, the 5-year OS (62% and 53%), PFS (63% and 30.3%), LC (87.5% and 52%), and DMFS (79.6% and 41.6%)., Conclusions: In this study population, HIF1a, Ki-67, CA-9, and GLUT1 expression did not predict treatment response or outcomes in locally advanced cervical cancer patients treated definitively with CRT. There was a nonstatistically significant trend towards worse outcomes with p53 expression., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Nanoparticles are becoming increasingly important against resistant superbugs including Pseudomonas aeruginosa infections., Aims: Exploration of Azithromycin as an adjunctive therapy to Ciprofloxacin for treatment of P. aeruginosa infections. Also, preparation of Ciprofloxacin-Azithromycin nanoparticles on chitosan nanocarrier (Cipro-AZM-CS) and assessment of its antimicrobial effect in vitro and in vivo., Methods: Detection of biofilm production and biofilm-specific antibiotic resistance ndvB and tssC1 genes was attempted. Minimal inhibitory concentration (MIC) and Minimum biofilm eradication concentration (MBEC) were done in vitro for assessment of P. aeruginosa planktonic and biofilm forms eradication, respectively. In In vivo study, Cipro-AZM-CS and free form were used to evaluate survival rate, wound contraction and bacterial load in mice after third degree burn., Results: All isolates were positive for biofilm production and ndvB and tssC1 genes. Majority of isolates (37, 74%) were extensively drug resistant. In the planktonic state, MIC values of Cipro-AZM free and CS forms were significantly lower than free Cipro MIC (P = 0.015 and P < 0.001 respectively). Also, Cipro-AZM free and CS MBEC values were significantly lower than that of free Cipro (P < 0.010 and P < 0.001 respectively). Furthermore, The MIC and MBEC values of free Cipro-AZM decreased significantly when challenged with Cipro-AZM-CS (P = 0.009 and P < 0.001 respectively). In vivo study combined free and Cipro-AZM-CS treated subgroups showed 100% mice survival with early resolution of infection and wound contraction (75%, 77.5% respectively) VS 45% for Cipro CS (P < 0.001)., Conclusion: Combined free and Cipro-AZM-CS showed promising results in vitro and in vivo overcoming high resistance of biofilm producing P. aeruginosa., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Aims: Several microbial toll-like receptor (TLR) ligands, bacterial DNA and bacterial cell wall fragments have been identified in the synovium of rheumatoid arthritis (RA) patients, proving bacterial involvement in the pathogenesis of RA. The current study aimed to verify that low dose polymyxin B could prevent the development of chronic inflammatory arthritis., Methods: Twelve days post adjuvant injection, Sprague-Dawley rats were treated twice weekly with methotrexate (0.5 mg/kg) or daily with polymyxin B (1 mg/kg) or with combination of both for 1 or 2 weeks. Arthritis progression was assessed by hind paw swelling, serum levels of tumor growth factor-1β (TGF-1β), tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (HS-CRP) and nuclear factor kappa B (NF-κB) were measured using ELISA. Cyclooxygenase-1 (Cox-1) and Cox-2 activities, as well as mRNA expression of TLR-2 and TLR-4 were determined. Histopathological examination of the ankle joint was performed as well as immunohistochemistry for anti-TLR-4. Histopathological assessment of toxic effects on the kidney was performed., Key Findings: Adjuvant arthritis led to a significant swelling of the hind paw and alteration in all serum parameters, TLR-2 and TLR-4 expression, as well as Cox-2 activity. These alterations were associated with histopathological changes of the joints. Polymyxin B reduced significantly all biomarkers of inflammation, showing better effect of the combination in most of the studied parameters, with minimal signs of nephrotoxicity., Significance: In conclusion, results showed that polymyxin B possesses significant anti-arthritic activity which may be attributed to inhibition of the TLR-4, NF-κB and Cox-2 signaling pathway., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Alopecia areata (AA) is an autoimmune form of nonscarring hair loss. The aim of the study was to assess the serum concentration of interferon gamma (IFN-γ) and CD8 cell expression in lesional skin biopsies in correlation with the disease severity, activity, duration, and trichoscopic findings in patients with AA. The study included 30 patients with AA and 15 age- and sex-matched healthy controls. Trichoscopy was performed and photographs were captured for the alopecic areas, and the enzyme-linked immunosorbent assay technique was used for serum level of IFN-γ assessment and immunohistochemistry for CD8 cells. The results obtained indicate that IFN-γ serum level in patients was significantly higher than that of control subjects, and significantly correlated with the activity status and the duration of the disease. CD8+ T cells infiltrate intensity significantly correlated with severity. Yellow dots (YDs), vellus hair, black dot, and exclamation marks were the most common trichoscopic findings. The presence of black dots significantly correlated to the disease activity, duration, serum IFN-γ, and CD8+ infiltrate intensity. The presence of YDs significantly correlated with the mean serum IFN-γ level. Exclamation marks significantly correlated with the disease activity and the degree of CD8+ infiltrate. In conclusion, trichoscopy could be a reliable indicator of the IFN-γ serum level and CD8+ T cell infiltrate intensity in AA patient., (© 2020 Wiley Periodicals LLC.)

Objectives: Nuclear factor kappa B (NFkB) is a transcription factor shown to confer treatment resistance in tumors. A previous report suggested an association between pretreatment NFkB and poorer outcomes for cervical cancer patients treated with chemoradiation therapy (CRT). We aimed to validate their findings in a larger patient cohort., Materials and Methods: This Institutional Review Board approved study included patients with locally advanced cervical cancer patients treated with CRT. Evaluation of both nuclear and cytoplasmic immunoreactivity for NFkB was scored semiquantitatively by 3 pathologists. Cytoplasmic positivity incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H-score), whereas nuclear positivity was assessed by percentage of positive cells. Outcomes were stratified by NFkB overexpression and tumor characteristics. Overall survival (OS), progression-free survival (PFS), distant metastases-free survival (DMFS), and local regional control (LC) were obtained using Kaplan-Meier and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained using Cox regression for both univariate and multivariate analyses., Results: The mean age was 51 years old and most (78.57%) had locally advanced disease. Five-year OS, PFS, LC, and DMFS in the entire cohort were 57.18% (confidence interval [CI], 34.06%-74.82%), 48.07% (CI, 25.50%-67.52%), 72.11% (CI, 49.96%-85.73%), and 62.85% (CI, 36.33%-80.82%), respectively. There was no significant association between NFkB expression (H-index ≥180) and 3-year and 5-year OS (P-value=0.34), PFS (P-value=0.21), LC (P-value=0.86), or DMFS (P-value=0.18)., Conclusions: Our study demonstrated that cytoplasmic NFkB-p65 expression (H-index ≥180) was associated with a nonstatistically significant trend toward poor clinical outcomes in locally advanced cervical cancer patients treated definitively with CRT.

Purpose: This study aimed to assess the association between pretreatment c-Met overexpression in local-regional advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), distant metastases (DM) control, and local-regional control (LC)., Patients and Methods: This Institutional Review Board-approved study included cervical cancer patients treated definitively and consecutively with CRT. Evaluation of cytoplasmic immunoreactivity for c-Met was performed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes, and incorporated both the intensity and percentage of immunoreactivity in invasive carcinoma (H score). Treatment outcomes were reviewed and reported. Outcomes were stratified by c-Met overexpression and tumor characteristics. OS, PFS, LC, and DC rates were obtained via the Kaplan-Meier method and differences between groups were evaluated by the log-rank test. Hazard ratios were obtained via Cox regression for both univariate and multivariate analyses., Results: The 5-year OS, PFS, LC, and DC were 57.18%, 48.07%, 72.11%, and 62.85%, respectively. Ten (35.7%) and 18 patients (64.3%) had c-Met H index >30 and<30, respectively. c-Met overexpression was significantly associated with worse 3- and 5-year OS (P=0.003), PFS (P=0.002), LC (P=0.01), and DC (P=0.0003). Patients with c-Met overexpression had a hazard ratio of 6.297, 5.782, 6.28, and 18.173 for the risks of death, disease progression, local recurrence, and DM, respectively., Conclusion: c-Met overexpression could be a potential predictive marker and therapeutic target for local-regional advanced cervical cancer patients treated definitively with CRT.

This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests. Quantification of NPs in tissues was done both by bulk inductively coupled plasma mass spectrometry (ICP-MS) analysis and by hard X-ray fluorescence microscopy. Both IV and IC NPs injection are feasible modalities for delivering NPs to VX2 liver tumors with comparable tumor accumulation. It is possible that this is an outcome of the fact that VX2 tumors are highly vascularized and hemorrhagic, and therefore enhanced permeability and retention (EPR) plays the most significant role in accumulation of nanoparticles in tumor tissue. It is, however, interesting to note that IV delivery led to increased sequestration of NPs by spleen and normal liver tissue, while IC delivery lead to more NP positive Kupffer cells. This difference is most likely a direct outcome of blood flow dynamics. Armed with this knowledge about nanoparticle delivery, we plan to test them as radiosensitizers in the future.

Purpose: Cancer is one of the leading causes of death, and thus, the scientific community has but great efforts to improve cancer management. Among the major challenges in cancer management is development of agents that can be used for early diagnosis and effective therapy. Conventional cancer management frequently lacks accurate tools for detection of early tumors and has an associated risk of serious side effects of chemotherapeutics. The need to optimize therapeutic ratio as the difference with which a treatment affects cancer cells versus healthy tissues lead to idea that it is needful to have a treatment that could act a the "magic bullet"-recognize cancer cells only. Nanoparticle platforms offer a variety of potentially efficient solutions for development of targeted agents that can be exploited for cancer diagnosis and treatment. There are two ways by which targeting of nanoparticles can be achieved, namely passive and active targeting. Passive targeting allows for the efficient localization of nanoparticles within the tumor microenvironment. Active targeting facilitates the active uptake of nanoparticles by the tumor cells themselves., Methods: Relevant English electronic databases and scientifically published original articles and reviews were systematically searched for the purpose of this review., Results: In this report, we present a comprehensive review of literatures focusing on the active targeting of nanoparticles to cancer cells, including antibody and antibody fragment-based targeting, antigen-based targeting, aptamer-based targeting, as well as ligand-based targeting., Conclusion: To date, the optimum targeting strategy has not yet been announced, each has its own advantages and disadvantages even though a number of them have found their way for clinical application. Perhaps, a combination of strategies can be employed to improve the precision of drug delivery, paving the way for a more effective personalized therapy.