BACKGROUND: To achieve delivery of a drug to tumors, folic acid (FA) was used as a targeting ligand to change nanocarriers. Since the folate receptor has more expression in several tumor types such as breast cancer. OBJECTIVES: The present study aimed to evaluate the effect of Doxorubicine-G2-FA (Dox-G2-FA) with in vitro assays. The abbreviation of G2 represents the second generation of dendrimer synthesis. METHODS: For this purpose, Dox-G2-FA was synthesized and mass spectroscopy was used to confirm the synthesized component. Also, MTT assay, flow cytometry, and gene expression assay by real-time PCR were used to evaluate cell viability, apoptosis, and necrosis. RESULTS: In this study, the effect of Dox and Dox-G2-FA on the expression of Bax, Bcl2 genes showed that there was a significant decrease in the expression of the Bcl2 gene in the Dox-G2-FA group compared to Dox and control groups(P<0. 05). Also, the results of flow-cytometry showed that apoptosis in the presence of Dox-G2-FA was greater than in the Dox group (P<0. 05). CONCLUSIONS: Therefore, it seems that the effect of Dox-G2-FA on apoptosis is better than the effect of Dox usage alone.

Objective: Drug delivery systems related to different cancer therapies is now expanding.Chitosan (CS) is currently receiving enormous interest for medical and pharmaceutical applications due to its biocompatibility in animal tissues. In this study, two nanogels were prepared from CS. Some of the critical factors such as controlling the release, adsorption and specially targeting drug delivery are considered while preparing the nanogels.Methods: Phosphorylated CS (PCS) and Myristilated CS (MCS) nanogels were prepared by reacting CS with tripolyphosphate (TPP) and Myristate as cross-linking agents respectively and then were loaded with Doxorubicin (DOX). The nanogels were characterized by different techniques such as scanning electron microscopy, dynamic light scattering and Fourier-transform infrared. The cytotoxicity of free DOX, MCS nanogels and DOX loaded MCS was evaluated by the MTT assay.Results: The result of DOX loading and releasing of the nanogels showed high loading capacity and drug loading efficiency of about 97%. Results indicated slow release of about 16-28% of DOX from PCS within 5 days and 18-40% from MCS within 15 days.DOX and MCS-DOX showed the same toxic effect on the prostate cancer cells (LNCaP).Conclusion: Both PCS and MCS nanogels were qualified on the basis of size, loading and releasing capacity.

Background: Neuroblastoma (NB), a malignant sympathetic nervous system cancer, is the second most common type of pediatric tumor. Increasing the number of NB death emerges to design a new strategy for NB treatment. Nowadays, the development of natural compounds has gradually increased due to their ability to apoptosis induction. Tea catechin, a flavonoid compound, is one of the natural combinations which inhibit tumor growth and enhance tumor cell apoptosis. In the current study, the effects of pure catechin, doxorubicin (DOX), and their combination on a cellular model of NB [BE(2)C cells] are perused. (NB) a malignant sympathetic nervous system cancer is the second most common type of pediatric tumor. Increasing the number of NB death emerges to design a new strategy for NB treatment. Nowadays, the development of natural compounds has gradually increased due to their ability to apoptosis induction. Tea catechin, a flavonoid compound, is one of the natural combinations which inhibit tumor growth and enhance tumor cell apoptosis. Objectives: In the current study, the effects of pure catechin, doxorubicin (DOX), and their combination on a cellular model of NB [BE(2)C cells] are perused. Methods: The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay was done to assess a response dose for each drug. Fluorescent Microscopic and cell cycle analyses were performed for apoptosis detection. Finally, Colony formation was performed to examine cell migration and invasion. Results: The MTT assay showed that catechin and DOX treatment inhibited the viability of the cells while the combination of their ineffective doses had more cytotoxic effects. However, these treatments could not inhibit the cell growth of the normal human fibroblast. Moreover, this combination reduced cell attachment, chromatin fragmentation, and G/S arrest in the cell cycle. The clonogenic assay demonstrated that colony size and numbers obviously reduced after ten days,therefore, Catchin and its combination with DOX suppressed cell capacities of clone formation and migration. Conclusions: These results suggest that catechin, DOX, and their combination may inhibit the proliferation, invasion, and migration of BE(2)C Neuroblastoma cells in vitro while inducing cell apoptosis by arresting the cell cycle.

ENGLISH: Doxorubicin (DOX) is one of the secondary metabolites of Streptomyces peucetius var. caesius. It is a common and effective chemotherapeutic agent used for the treatment of different diseases, including lymphoma, leukemia, breast cancer, and solid tumors. However, this medicine causes cardiotoxic side effects, which limit its clinical application. The present study examined the cardiomyopathy induced by DOX via echocardiography and transmission electron microscopy (TEM). The main objective was to evaluate the capacity of echocardiography and TEM as diagnostic tools for DOX-induced cardiotoxicity. Moreover, the correlation between intracellular and functional changes due to cardiotoxicity was assessed in a rat model. Cardiomyopathy was induced in rats by two cumulative doses of DOX. Group I received DOX 12 [i. e., 12 mg/kg, intraperitoneal (IP)] and group II received DOX 15 (i. e., 15 mg/kg, IP) in six equal doses over two weeks. Group III as the control (Ctrl) group received normal saline as a vehicle. Mortality during the study was only observed in the DOX 15 group. The echocardiographic assessments revealed significant changes in ejection fraction, fractional shortening, and heart rate in the groups which received DOX. In addition, severe cardiac arrhythmia was evident in DOX-treated groups. Remarkable adverse effects, such as moderately degenerated cells and inflated mitochondria were observed in the TEM analysis of rat hearts in the DOX groups. The present study indicated that rat models are suitable for investigating DOX-induced cardiomyopathy, especially at the dose of 12 mg/kg. Furthermore, echocardiography and TEM examinations were found to be valuable methods for the determination of cardiotoxicity in rats due to DOX. FRENCH: Ré sumé : La doxorubicine (DOX) est l'un des mé tabolites secondaires de Streptomyces peucetius var. caesius. La DOX est un agent chimiothé rapeutique commun et efficace utilisé pour le traitement de diffé rentes maladies, y compris le lymphome, la leucé mie, le cancer du sein et les tumeurs solides. Cependant, ce mé dicament provoque des effets secondaires cardiotoxiques, ce qui limite son application clinique. La pré sente é tude a examiné la cardiomyopathie induite par la DOX par é chocardiographie et microscopie é lectronique à transmission (MET). L'objectif principal é tait d'é valuer la capacité de l'é chocardiographie et de la MET comme outils de diagnostic de la cardiotoxicité induite par la DOX. De plus, la corré lation entre les changements intracellulaires et fonctionnels causé s par la cardiotoxicité de cette substance a é té é valué e dans un modè le de rat. La cardiomyopathie a é té induite chez le rat par l’ injection de deux doses cumulé es de DOX. Le groupe I a reç u DOX 12 [12 mg/kg, intrapé ritoné al (IP)] et le groupe II a reç u DOX 15 (15 mg/kg, IP) en six doses é gales sur deux semaines. Le groupe III (groupe té moin, Ctrl) a reç u une solution saline normale comme vé hicule. Au cours de cette é tude, la mortalité n’ a é té observé e que dans le groupe DOX 15. L'é valuation é chocardiographique a ré vé lé des changements significatifs dans la fraction d'é jection, le raccourcissement fractionnaire et la fré quence cardiaque dans les groupes traité s avec la DOX. De plus, ces derniers montraient une arythmie cardiaque sé vè re é vidente. L'analyse MET sur le coeur de rats traité s avec la DOX a montré des effets indé sirables remarquables comme des cellules modé ré ment dé gé né ré es et des mitochondries gonflé es. Cetteeé tude montraitque les modè les de rat conviennent pour é tudier la cardiomyopathie induite par la DOX, en particulier à la dose de 12 mg/kg. De plus, l'é chocardiographie et les examens MET se sont ré vé lé s ê tre des mé thodes pré cieuses pour la dé termination de la cardiotoxicité de la DOX chez le rat.

English: In China, Japan, and Korea, Panax ginseng has been used in traditional medicine for thousands of years. Panax is a plant used as a general tonic or adaptogen for chronically ill patients. The current study evaluated the cytotoxicity of Panax ginseng extract (PGE). Different cell lines (HCT-116, LNCaP, and normal cell line VERO) were treated with different inhibitory agentsat different concentrations (1000, 500, 250, 125, 62. 5, and 31. 25 μ, g/ml) as follows: G1 (Methanol Panax ginseng extract, PGE), G2 (Doxorubicin, DOX), and G3 (Methanol Panax ginseng extract +DOX, PDD). Each inhibitory agent group was used to treat the cancerous cell lines HCT-116, LNCaP, and normal cell line (VERO) to obtain IC50% by MTT assay. The inhibitory ability of the 1000 μ, g/ml PGE was significantly increased in all the three-cell lines compared with other concentrations. The recorded data revealed that the inhibition ability of PGE and Doxorubicin towards the HCT-116 cell line significantly increased compared with the other cell lines. The interaction between different PGE concentrations and cell lines showed that the 1000 μ, g/ml PEG had the highest inhibitory effects on HCT-116 compared with other combinations. The interaction between different DOX concentrations and different types of cell lines showed that the 1000 μ, g/ml DOX had the highest inhibitory effects on LNCap compared with other combinations. The PGD inhibition ability reflected a significantly higher difference toward the HCT-116 cell line as compared with other cell lines. IC50% is the concentrations (μ, g/ml) to kill 50% of cell line. It was calculated by MTT assay for three cell lines: HCT-116, LNCaP, and VERO. The rate of effectiveness of the inhibitory factors (PGE, DOX, and PGD) showed highly significant differences toward the cell line HCT-116 compared to the other cell lines. This indicates the safety of the PGE compound and its low toxicity toward normal cells, quite the opposite of cancer cells as compared to the common drug DOX and combined PGD (PGE+DOX). PGD combined with DOX (PGE + DOX) showed antagonistic results toward the HCT116, LNCaP, and VERO cell lines, while UDE combined with DOX (UDE+DOX) showed synergistic activity. (French: En Chine, au Japon et en Coré, e, le Panax ginseng est utilisé,en mé, decine traditionnelle depuis des milliers d'anné, es. Panax est une plante utilisé, e comme tonique gé, né, ral ou adaptogè, ne pour les patients atteints de maladies chroniques. La pré, sente é, tude a é, valué,la cytotoxicité,de l'extrait de Panax ginseng (EPG). Diffé, rentes ligné, es cellulaires (HCT-116, LNCaP et ligné, e cellulaire normale VERO) ont é, té,traité, es avec diffé, rents agents inhibiteurs à,diffé, rentes concentrations (1000, 500, 250, 125, 62. 5 et 31. 25 μ, g/ml) comme suit: G1 (Extrait mé, thanol Panax ginseng, EPG), G2 (Doxorubicine, DOX) et G3 (Extrait mé, thanol Panax ginseng +DOX, PDD). Chaque groupe d'agents inhibiteurs a é, té,utilisé,pour traiter les ligné, es cellulaires cancé, reuses HCT-116, LNCaP et la ligné, e cellulaire normale (VERO) pour obtenir une CI50% par dosage MTT. La capacité,inhibitrice de l'EPG à,1000 g/ml a é, té,significativement augmenté, e dans toutes les ligné, es à,trois cellules par rapport aux autres concentrations. Les donné, es enregistré, es ont ré, vé, lé,que la capacité,d'inhibition de l'EPG et de la doxorubicine envers la ligné, e cellulaire HCT-116 a considé, rablement augmenté,par rapport aux autres ligné, es cellulaires. L'interaction entre diffé, rentes concentrations de l'EPG et des ligné, es cellulaires a montré,que le PEG à,1000 ug/ml avait les effets inhibiteurs les plus é, levé, s sur HCT-116 par rapport à,d'autres combinaisons. L'interaction entre diffé, rentes concentrations de DOX et diffé, rents types de ligné, es cellulaires a montré,que la DOX à,1000 g/ml avait les effets inhibiteurs les plus é, levé, s sur LNCap par rapport à,d'autres combinaisons. La capacité,d'inhibition du PGD reflé, tait une diffé, rence significativement plus é, levé, e envers la ligné, e cellulaire HCT-116 par rapport aux autres ligné, es cellulaires. IC50% est la concentration (μ, g/ml) pour tuer 50% de la ligné, e cellulaire. Il a é, té,calculé,par dosage MTT pour trois ligné, es cellulaires: HCT-116, LNCaP et VERO. Le taux d'efficacité,des facteurs inhibiteurs (EPG, DOX et PGD) a montré,des diffé, rences trè, s significatives envers la ligné, e cellulaire HCT-116 par rapport aux autres ligné, es cellulaires. Cela indique la sé, curité,du composé,EPG et sa faible toxicité,envers les cellules normales, tout à,fait le contraire des cellules cancé, reuses par rapport au mé, dicament commun DOX et au PGD combiné,(EPG + DOX). Le PGD combiné,à,la DOX (EPG + DOX) a montré,des ré, sultats antagonistes envers les ligné, es cellulaires HCT116, LNCaP et VERO, tandis que l'UDE combiné,à,la DOX (UDE + DOX) a montré,une activité,synergique. )

Background and Objectives: CLL (Chronic Lymphocytic Leukemia) is the most common form of leukemia in the western world and because of prolonged survival of patients, the prevalence is high. Chemotherapy is usually not indicated in early and stable disease and using chlorambucil with or without steroids has been the drug of choice in the treatment of CLL for many years .Clinical studies have shown that using fludarabin can cause a complete response in significant number of untreated and/or previously treated CLL patients. The aim of this study was evaluation of CLL patients and determining the effects of treatment with fludarabin. Materials and Methods: A retrospective (descriptive/cross sectional) study of CLL patients who were admitted to Hematology and Oncology Research Center of Tabriz University of Medical Sciences, between 1995-2005 was made and 126 patients enrolled. Collection of data was carried out according to special questionnaire and response to fludarabin was analyzed by SPSS-11 software.Results: The mean age of patients at diagnosis was 63.7±8.9 years, 69.8% were males.Illness and fatigue were the most common presenting symptoms in 54% and lymphadenopathy was the most common clinical sign in 88.9%. Most of the patients were in stage C in Binet system (52.4%) and/or stage IV in Rai system (44.4%). Chemotherapy with chlorambucil and prednisolone was the most common regimen used (60.3%) and 49.2% of patients were in partial remission with this treatment. Forty two patients treated with fludarabin and 50% were in partial remission, 35% in static disease, 10% in progressive disease and 5% in complete remission (P=0.053).Conclusion: The median survival with fludarabin was 43.9±27.2, months and in the case of chlorambucil + prednisolone and cyclophosphamide + vincristine + prednisone (CVP) or cyclophosphamide + vincristine + prednisone + doxorubicine (CHOP), it was 45±26.5, months and 50±32.2, months respectively (P>0.05). P value in relation with survival and response to fludarabin was 0.05. Above all, fludarabin is the treatment of choice as first and second line therapy and for patients who have failed therapy with standard regimens.