Search

In metastatic breast cancer (MBC), the conventional doxorubicin (DOX) has various problems due to lack of selectivity with subsequent therapeutic failure and adverse effects. DOX- induced cardiotoxicity is a major problem that necessitates the presence of new forms to decrease the risk of associated morbidity. Nanoparticles (NPs) are considered an important approach to selectively increase drug accumulation inside tumor cells and thus decreasing the associated side effects. Tumor cells develop resistance to chemotherapeutic agents through multiple mechanisms, one of which is over expression of efflux transporters. Various NPs have been investigated to overcome efflux mediated resistance. To date, only liposomal doxorubicin (LD) and pegylated liposomal doxorubicin (PLD) have entered phase II and III clinical trials and FDA- approved for clinical use in MBC. This review addresses the effects of LD and PLD on the hematological and palmar-plantar erythrodysesthesia (PPE) in anthracycline naïve and pretreated MBC patients. For evidence, studies to be included in this review were identified through PubMed, Cochrane and Google scholar databases. The results derived from: four phase III clinical trials that compared LD with the conventional DOX in naïve MBC patients, and ten non-comparative clinical trials investigated LD and PLD as monotherapy or combination in pretreated MBC. This work confirmed the cardiac tolerability profile of LD and PLD versus DOX, while hematological and skin toxicities were more common. Other DOX-NPs in preclinical trials were discussed in a chronological order. Finally, the modern preclinical development framework for DOX includes exosomal DOX (exo-DOX). Exosomal NPs are non-toxic, non-immunogenic, and can be engineered to have high cargo loading capacity and targeting specificity. These NPs have not been investigated clinically. Our study shows that the full clinical potentiality of DOX-NPs remains to be addressed to move the field forward.

Introduction Testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) became the preferable techniques for solving the problem of azoospermic men. Non-invasive techniques are needed to predict sperm retrieval chance before TESE to avoid the psychological and physiological problems that may be developed. Aim To investigate the correlation between serum, seminal and testicular leptin levels and sperm retrieval in functional azoospermic men. Methods The study included 61 men classified into 4 groups; normozoospermia (NOR), obstructive azoospermia (OA), positive non-obstructive azoospermia (NOA (+)) and negative non-obstructive azoospermia (NOA (−)). Blood FSH, LH, Prolactin, Free and Total testosterone levels plus serum and seminal leptin levels were measured for all groups. For azoospermic groups, TESE and testicular leptin level were applied. Main outcome measures Both OA and NOR groups were used as control groups. The prediction accuracy for FSH and serum, seminal and testicular leptin was compared by receiver operating characteristic (ROC) curve analysis. Results There were no significant differences in serum leptin levels among the four groups. Azoospermic groups showed higher seminal leptin levels than the NOR group. Seminal and Testicular leptin levels of NOA (−) men were significantly increased in comparison with OA and NOA (+) men. There was a significant negative correlation between serum leptin and total testosterone concentrations, and a significant positive correlation between testicular and seminal leptin concentrations. In ROC curve; for differentiation between positive and negative NOA, areas under the curve (AUC) of testicular and seminal leptin were greater than that of serum leptin. The combination of seminal leptin with FSH gave AUC greater than that of FSH alone. Conclusion There is a role for leptin in spermatogenesis, and seminal leptin can be used as a good assistant marker to increase the prediction accuracy for sperm retrieval in NOA men especially in combination with FSH.

Background Hepatocellular carcinoma [HCC] is the third leading cause of death from cancer worldwide. In Egypt, HCC accounts for about 4.7% of chronic liver disease. To date, no controlled studies have evaluated the Sorafenib efficacy in comparison to no treatment in HCC patients whose etiology of HCV genotype 4 (The most prevalent hepatitis C virus genotype in Egypt). Methods A multicenter prospective controlled interventional study. 110 Patients were evaluated for overall survival [OS], Progression-free survival [PFS], safety and quality of life [QOL] using FACT Hepatobiliary Symptom Index [FHSI-8] questionnaire. NCT02971696. Results Out of 110 patients enrolled, only 55 completed the trial; sorafenib [n = 35], no-treatment control group [n = 20]. The one year OS was 0.0% versus 75.5% [p = 0.008] in control and sorafenib respectively. Median PFS was 5 months versus 12 months in control group and sorafenib respectively [p = 0.008]. Sorafenib group HR for developing progression was 2.35; [95% [CI], 1.19 to 4.62; P = 0.014]. QOL scores [FHSI-8] was significantly different between the 2 groups [F = 4.455, p = 0.047]. Most observed side effects of sorafenib were; Diarrhea [n = 15] and hand-foot syndrome [n = 12]. Conclusions Sorafenib treatment showed a better outcome OS, PFS and QOL as compared to no-treatment in Egyptian patients with advanced Hepatocellular Carcinoma. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Some 4-phenylthiazole derivatives were tested as corrosion inhibitors for 304L stainless steel in 3.0 M HCl using weight loss and galvanostatic techniques. The results showed that the inhibition efficiency increases with increasing the concentration of the 4-phenylthiazole derivatives. Polarization measurements showed that these derivatives act as mixed-type inhibitors. The adsorption of these inhibitors on the surface of stainless steel follows Temkin’s adsorption isotherm and kinetic model. The effect of temperature on the corrosion was investigated by the weight loss method and some thermodynamic parameters were calculated. The synergistic influence caused by thiocyanate ion on the inhibition of corrosion of 304L stainless steel in 3.0 M HCl in the presence of 4-phenylthiazole derivatives has been studied using weight loss method. The inhibition action of these 4-phenylthiazole derivatives was discussed in terms of its adsorption on the metal surface.

Voltage instability problems in power systems today are, in many countries, one of the major concerns in power system planning and operation. This paper presents the assessment of voltage stability margins for Muscat power system under normal operating condition and under contingencies. The modal analysis method is applied to identify the weak buses in the system, which could lead to voltage instability. These weak buses are selected as the best locations for applying remedial actions to enhance the stability margins. The results show that the buses at South Batna load area are the weakest buses in the system. The results also show that an increase in load demand on that area without an adequate increase of reactive power could lead to voltage collapse. Shunt VAR compensations (remedial action) are installed at the weakest buses to enhance the system stability margins. The results presented in this paper are obtained using a matlab computer program developed by the authors.

Tuning of static var compensator (SVC) stabilizers traditionally assumes that the system loads are voltage dependent with fixed parameters. However, the load parameters are generally uncertain. This uncertain behavior of load parameters can de-tune the stabilizer gain-settings, consequently SVC stabilizer with fixed gains can be adequate for some load parameters but contrarily reduce system damping and contribute to system instability with loads having other parameters. An adaptive network based fuzzy inference system (ANFIS) for an SVC stabilizer is presented in this paper to improve the damping of power systems in the presence of load model parameters uncertainty. Takagi and Sugeno's fuzzy if-then rules and an adaptive feed-forward neural network with supervised learning capability are used in the ANFIS. The proposed ANFIS is trained over a wide range of typical load parameters in order to adapt the gains of the SVC stabilizer. A MATLAB computer simulation is used to show the effectiveness of the proposed ANFIS SVC stabilizer. The simulation results show that the tuned gains of the SVC stabilizer using the ANFIS can provide better damping than the conventional fixed-gains SVC stabilizer.

This paper presents an artificial neural network (ANN)-based technique for tuning a damping controller for a static var compensator (SVC) to improve the damping of power systems over a wide range of typical load models. A proportional–integral (PI) controller is considered for the damping controller and its parameters are determined using the pole-placement technique. The types and characteristics of loads vary seasonally, and in some cases change over a day; consequently, a damping controller designed with fixed parameters can be adequate for some loads but, contrarily, can contribute to system instability with loads having other extreme characteristics. The developed ANN-based technique uses pre-determined system load characteristics combined with other measured system conditions as continuous inputs. Based on such information, the ANN technique adjusts the SVC damping controller parameters to assure good damping and system stability for the prevailing conditions. The proposed ANN technique has been applied to tune the parameters of the SVC damping controller for two power systems. The results show that the load model parameters have a considerable effect on the tuned parameters of the damping controller. Computer simulations performed on the two power systems show that the tuned parameters of the SVC damping controller using the ANN technique can provide better damping than the fixed parameters damping controller.

A novel approach using an artificial neural network (ANN) for tuning a static var compensator (SVC) controller over a wide range of load models is presented in this paper. To enhance power system damping over a wide range of load models, it is desirable to adapt the SVC controller gain in real time based on load models. To do this, online measurements of load parameters which are representative of load models are chosen as the input signals to the neural network. The output of the neural network is the desired gain of the SVC controller. The neural network, once trained by a set of input-output patterns in the training set, can yield a proper SVC controller gain under any load model. Simulation results show that the tuning gain of a SVC controller using the ANN approach can provide better damping of the power system over a wide range of load models than the fixed-gain controller.

In this paper, novel artificial neural network (ANN) based weather-load and weather-energy models have been developed to forecast electric load and energy for 24 months ahead. A set of weather and other variables which have been identified for both models together with their correlations and contribution to the forecasted variable is reported. The proposed ANN models have been applied to historical energy, load, and weather data available for the Muscat power system from 1986 to 1990. Forecast results, when compared with the actual data for 1991–1992, show that monthly electric energy and load can be predicted within a maximum error of 6% and 10%, respectively, even with forecasted weather. The proposed ANN models provide better accuracy than previously developed models.

Introduction: The burden of hepatocellular carcinoma (HCC) has been increasing in Egypt in the past 10 years. Sorafenib which is the only approved systemic agent for advanced HCC is not affordable economically for the vast majority of HCC patients in Egypt; a preliminary study suggested that capecitabine may be effective in advanced HCC thus we explored the use of capecitabine monotherapy for HCC in this phase 2 study.

Purpose: The only approved systemic therapy for patients with advanced hepatocellular carcinoma (HCC) till now is sorafenib; however, this should be within strict selection criteria. We have thus conducted this retrospective analysis of our HCC database to determine the adherence to this selection criteria in patients referred to our institute for sorafenib treatment. Methods: HCC patients treated at Ain shams university hospitals, clinical oncology department (Cairo, Egypt) in the period between2010-2012 were reviewed. Eligible patients were those who had confirmation of the diagnosis and referred to receive sorafenib for advanced HCC (BCLC C disease). We investigated the distribution of baseline demographic and clinicopathological factors (age, gender, child status, performance score, cause of chronic liver disease, median baseline albumin, total bilirubin, INR and alpha fetoprotein level). Results: 41 patients were included in the analysis fulfilling the inclusion criteria. At a median follow up period of 13 months, the median PFS for the whole group was 6.1 months (95% CI 3.2-8.7); the median OS for the whole group is 7.05 months (95% CI 5.58-8.43). Median age was 53.5 years (range 33-75), all our patients were males, HCV was the case of chronic liver disease in 96% while NAFLD was the cause in 4%, 53% of our patients have ECOG performance score of 1 while 47% have a score of 2. Macroscopic vascular invasion were present in 38% while extrahepatic spread was present in 23%, 30% have child A disease while 34% have early B disease(score =7) and 36% have late B disease. Median baseline albumin is 3.2 (2.5-4.2), total bilirubin 1 (0.6-3), alpha fetoprotein 989 (15-28500) Conclusion: According to our experience, many cases referred to receive sorafenib are not thoroughly evaluated; proper pretreatment assessment and cost effectiveness evaluation is mandatory before prescribing costly medications in palliative indications.

Background: According to the results of a number of phase 3 randomized studies, sorafenib is the only approved systemic therapy for advanced HCC; however the issue of high economic cost remains challenging particularly in low income countries like Egypt; thus we have conducted this retrospective analysis of our HCC patients treated with sorafenib to determine which patients benefit most from this costly treatment.

Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G + T arm. The primary efficacy endpoint was a comparison of progression-free survival (PFS) between the combination arms and G alone (80% power to detect 50% improvement in PFS with one-sided alpha of 10%). Summary PFS outcome has previously been reported; more detailed PFS as well as the initial overall survival (OS) data are presented. Results 214 pts were treated; 164 (77%) Stage IV and 50 (23%) Stage IIIB. Median age 65 (range 29-86); 126 M/88 F; 40% ECOG 0/60% ECOG 1. Receiving 6 or more cycles: 32% G; 45% G + T240; 55% G + T340. Median PFS was 3.6 mo in G vs 5.5 mo in G + T240 (p = 0.031) and 6.0 mo in G + T340 (p = 0.008). Poorer prognostic factors (older age, poorer performance status, reduced albumin) were associated with larger treatment effect. Median OS was 7.0 mo in G vs 9.0 in G + T240 and 9.5 mo in G + T340. RECIST best response was 12% in G vs 17% in G + T240 and 27% in G + T340. CA19-9 decreases were significantly greater G + T340. A >50% CA19-9 decrease was 52% with G vs 50% with G + T240 and 70% with G + T340. AEs leading to discontinuation were: 16% G, 15% G + T240 and 11% G + T340. Rash (45% in G + T340) and stomatitis (36% in G + T340) were greater in combination, 4 pts Grade 3 rash. Grd 3/4 thrombocytopenia were 11% G, 39% G + T240 and 59% G + T340 and Grd 3/4 neutropenia were 28% G, 56% G + T240 and 59% G + T340. Conclusions The combination of G plus TH-302 improved the efficacy of G. A TH-302 dose of 340 mg2 was identified for future studies. Skin and mucosal toxicity and myelosuppression were the most common TH-302 related AEs with no increase in treatment discontinuation. Disclosure All authors have declared no conflicts of interest.

Introduction This prospective, multicenter, phase III trial compares the efficacy and safety of celiac neurolysis versus palliative radiotherapy for pain control in patients with advanced pancreatic carcinoma. Methods 40 patients with advanced pancreatic carcinoma presented with epigastric pain had their numeric rating pain scores controlled to the range (0-2) by opioids. After pain control, patients were randomly assigned into two groups. Group I (n=22) received local radiotherapy. Group II (n=18) underwent fluoroscopic celiac neurolysis. After treatment, there was an attempt to gradually withdraw the daily dose of opioids to the least effective dose that maintains the pain scores at (0-2) unchanged. Evaluation was done at the 6th and the 12th weeks from neurolysis and radiation therapy. The comparison between both groups was based on the opioid milligrams that could be withdrawn. The adverse effects from radiation therapy, opioids and celiac neurolysis were monitored and reported. Results At the 6th week evaluation, 23% of patients in group I versus 88.8% in group II had 100% opioid withdrawal. By the 12th week, 0% of patients in group I versus 72.2% in group II had 100% opioids withdrawal. Conclusion A high statistical significant difference (P

Introduction The only approved systemic therapy for patients with advanced hepatocellular carcinoma (HCC) till now is sorafenib. a preliminary study suggested that capecitabine, an oral fluoropyrimidine may be effective in advanced HCC. We have testified this hypothesis in this phase 2 study. Methods The Clinical oncology department at Ain Shams University carried out a phase 2, open label trial. 52 patients with advanced HCC who had not received previous systemic treatment were randomly assigned between September 2010 and April 2011 to receive either sorafenib (at a dose of 400 mg twice daily) or capecitabine 1000mg/m2 twice daily (day1-day14). Primary outcomes were progression free survival. Secondary outcomes included the overall survival and safety. Results Median overall survival was 7.05 months in the sorafenib group and 5.07 months in the placebo group (hazard ratio in the capecitabine group, 2.36; 95% confidence interval, 1.174-4.74; P Conclusion In patients with advanced HCC, capecitabine is inferior to sorafenib in terms of median progression free survival and overall survival and it should not be used alone for the treatment of advanced HCC but rather combination therapy with sorafenib should be considered.