Comparative Analysis of Dosimetry: IMRT versus 3DCRT in Left-Sided Breast Cancer Patients with Considering Some Organs in Out - of - Field Borders.

Purpose: The local management approach for node-positive breast cancer has undergone substantial evolution. Consequently, there exists a pressing need to enhance our treatment strategies by placing greater emphasis on planning and dosimetric factors, given the availability of more conformal techniques and delineation criteria, achieving optimal goals of radiotherapy treatment. The primary aim of this article is to discuss how the extent of regional nodal coverage influences the choice between IMRT and 3D radiation therapy for patients. Patients and Methods: A total of 15 patients diagnosed with left breast cancer with disease involved lymph nodes were included in this study. Delivering the recommended dose required the use of a linear accelerator (LINAC) with photon beams energy of 6 mega voltage (6MV). Each patient had full breast radiation using two planning procedures: intensity-modulated radiotherapy (IMRT) and three-dimensional radiotherapy (3D conformal). Following the guidelines set forth by the Radiation Therapy Oncology Group (RTOG), the planned treatment coverage was carefully designed to fall between 95% and 107% of the recommended dose. Additionally, Dose Volume Histograms (DVHs) were generated the dose distribution within these anatomical contours. Results and Conclusion: The DVH parameters were subjected to a comparative analysis, focusing on the doses absorbed by both Organs at Risk (OARs) and the Planning Target Volume (PTV). The findings suggest that low doses in IMRT plan might raise the risk of adverse oncological outcomes or potentially result in an increased incidence of subsequent malignancies. Consequently, the adoption of inverse IMRT remains limited, and the decision to opt for this therapy should be reserved for situations where it is genuinely necessary to uphold a satisfactory quality of life. Additionally, this approach helps in reducing the likelihood of developing thyroid problems and mitigates the risk of injuries to the supraclavicular area and the proximal head of the humerus bone.

Biodiversity and biological applications of marine actinomycetes-Abu-Qir Bay, Mediterranean Sea, Egypt.

BACKGROUND: The ability of actinomycetes to produce bioactive secondary metabolites makes them one of the most important prokaryotes. Marine actinomycetes are one of the most important secondary metabolites producers used for pharmaceuticals and other different industries. RESULTS: In this study, the promising actinomycetes were isolated from Abu-Qir Bay. Four different media named as starch nitrate, starch casein, glycerol asparagine, and glycerol glycine were used as a preliminary experimental media to study the role of the medium components on the counts of actinomycetes in sediment samples. The results indicated that starch casein medium reported the highest counts (30-63 CFU/g) in all the tested sites. Lower counts were detected on starch nitrate and glycerol asparagine. On the other hand, glycerol glycine medium gave the lowest counts (15-48 CFU/g). Abu-Qir8 harbored the highest average count of actinomycetes (63 CFU/g), followed by Abu-Qir1 (48 CFU/g). The lower counts were detected in Abu-Qir5 and Abu-Qir7 (26 and 29 CFU/g, respectively). A total of 12 pure obtained actinomycetes isolates were subjected to morphological, physiological, and biochemical characterization. The selected actinobacterial isolates were subjected to numerical analysis, and the majority of isolates were grouped into four main clusters (A, B, C, & D), and each of them harbored two isolates; additionally, four isolates did not cluster at this similarity level. Isolate W4 was carefully chosen as the most promising pigment and antimicrobial agent's producer; the produced pigment was extracted and optimized by statistical experiments (PBD & BBD) and was tested for its anti-inflammatory activity. The results showed anti-inflammatory effect and prevented the denaturation of BSA protein at a concentration much higher than the safe dose and increased with increasing the pigment concentration. CONCLUSION: Marine actinomycetes play a vital role in the production of novel and important economic metabolites that have many industrial and pharmaceuticals applications. Streptomyces genera are the most important actinomycetes that produce important metabolites as previously reported.

Exploring the antimicrobial, antiviral, antioxidant, and antitumor potentials of marine Streptomyces tunisiensis W4MT573222 pigment isolated from Abu-Qir sediments, Egypt.

Due to the therapeutic importance of microbial pigments, these pigments are receiving the attention of researchers. In this present study 60 isolates were isolated from sediments of Abu-Qir coast of the Mediterranean sea, Alexandria, Egypt, out of which 12 were considered as pigmented actinomycetes. Streptomyces sp. W4 was characterized by small round green pigmented colonies when grown on starch-casein agar medium. The green pigment was extracted using a mixture of acetone-methanol (7:3 v/v). The antimicrobial, antioxidant, antiviral, and anticancer activities of the green pigment produced by Streptomyces sp.W4 were investigated. The pigment was characterized using FTIR, Raman spectroscopy, EDX and GC-MS. The results revealed that the pigment has antibacterial and antifungal activity and also showed inhibition of HAV 78% but its antiviral activity against the Adenovirus was weak. The results proved the safety of the pigment toward normal cells and anticancer activity against three different cancer cell lines HepG-2 (liver cancer cell line), A549 (lung cancer cell line), and PAN1 (pancreas cancer cell line). The pigment was combined with 9 antibiotics and then tested against the Gram-negative bacterium Enterococcus faecalis using disc diffusion bioassay. LEV showed an antagonistic effect, while CXM and CIP showed a synergistic effect.

Praziquantel-encapsulated niosomes against Schistosoma mansoni with reduced sensitivity to praziquantel. / Niosomas encapsulados en prazicuantel contra Schistosoma mansoni con sensibilidad reducida al prazicuantel

INTRODUCTION: Praziquantel (PZQ) is the only commercially available drug for schistosomiasis. The current shortage of alternative effective drugs and the lack of successful preventive measures enhance its value. The increase in the prevalence of PZQ resistance under sustained drug pressure is, therefore, an upcoming issue. OBJECTIVE: To overcome the tolerance to PZQ using nanotechnology after laboratory induction of a Schistosoma mansoni isolate with reduced sensitivity to the drug during the intramolluscan phase. MATERIALS AND METHODS: Shedding snails were treated with PZQ doses of 200 mg/kg twice/ week followed by an interval of one week and then repeated twice in the same manner. The success of inducing reduced sensitivity was confirmed in vitro via the reduction of cercarial response to PZQ regarding their swimming activity and death percentage at different examination times. RESULTS: Oral treatment with a single PZQ dose of 500 mg/kg in mice infected with cercariae with reduced sensitivity to PZQ revealed a non-significant reduction (35.1%) of total worm burden compared to non-treated control mice. Orally inoculated PZQ-encapsulated niosomes against S. mansoni with reduced sensitivity to PZQ successfully regained the pathogen's sensitivity to PZQ as evidenced by measuring different parameters in comparison to the non-treated infected animals with parasites with reduced sensitivity to PZQ. The mean total worm load was 1.33 ± 0.52 with a statistically significant reduction of 94.09% and complete eradication of male worms. We obtained a remarkable increase in the percentage reduction of tissue egg counts in the liver and intestine (97.68% and 98.56%, respectively) associated with a massive increase in dead eggs and the complete absence of immature stages. CONCLUSION: PZQ-encapsulated niosomes restored the drug sensitivity against laboratory-induced S. mansoni adult worms with reduced sensitivity to PZQ.

Introducción. El prazicuantel es el único fármaco disponible comercialmente para la esquistosomiasis. La escasez actual de medicamentos alternativos y la falta de medidas preventivas eficaces aumentan su valor. La creciente prevalencia de la resistencia al prazicuantel bajo una presión prolongada del fármaco es, por tanto, un tema emergente. Objetivos. Superar la tolerancia al prazicuantel mediante nanotecnología después de la inducción en laboratorio de un aislamiento de Schistosoma mansoni con sensibilidad reducida al fármaco durante la fase intramolusco. Materiales y métodos. Los caracoles que liberaban cercarias se trataron con prazicuantel en dosis de 200 mg/kg dos veces por semana, seguidas de un intervalo de una semana, y luego se repitieron dos veces de la misma manera. La inducción exitosa de la sensibilidad reducida se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel con respecto a su actividad de natación y el porcentaje de muerte en diferentes momentos de examen. El éxito en inducir una menor sensibilidad se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel. Resultados. El tratamiento oral con una dosis única de prazicuantel de 500 mg/kg en ratones infectados con cercarias con sensibilidad reducida al prazicuantel, reveló una reducción no significativa (35,1 %) de la carga total de gusanos en comparación con los ratones de control no tratados. Los niosomas encapsulados en prazicuantel inoculados por vía oral contra S. mansoni con sensibilidad reducida al prazicuantel, permitieron reestablecer con éxito la sensibilidad del patógeno al medicamento, como lo demostró la medición de diferentes parámetros en comparación con los animales infectados no tratados con parásitos con sensibilidad reducida a prazicuantel. La carga media total de gusanos fue de 1,33 ± 0,52, con una reducción estadísticamente significativa del 94,09 %, y la erradicación completa de los gusanos machos adultos. Se obtuvo un aumento notable en el porcentaje de reducción del recuento de huevos en el tejido del hígado y el intestino (97,68 % y 98,56 %, respectivamente), asociado con un aumento masivo de huevos muertos y ausencia total de estadios inmaduros. Conclusión. Los niosomas encapsulados en prazicuantel restauraron la sensibilidad al fármaco contra gusanos adultos de S. mansoni con sensibilidad reducida al prazicuantel inducida en el laboratorio.

Praziquantel-encapsulated niosomes against Schistosoma mansoni with reduced sensitivity to praziquantel / Niosomas encapsulados en prazicuantel contra Schistosoma mansoni con sensibilidad reducida al prazicuantel

Introduction: Praziquantel (PZQ) is the only commercially available drug for schistosomiasis. The current shortage of alternative effective drugs and the lack of successful preventive measures enhance its value. The increase in the prevalence of PZQ resistance under sustained drug pressure is, therefore, an upcoming issue. Objective: To overcome the tolerance to PZQ using nanotechnology after laboratory induction of a Schistosoma mansoni isolate with reduced sensitivity to the drug during the intramolluscan phase. Materials and methods: Shedding snails were treated with PZQ doses of 200 mg/kg twice/ week followed by an interval of one week and then repeated twice in the same manner. The success of inducing reduced sensitivity was confirmed in vitro via the reduction of cercarial response to PZQ regarding their swimming activity and death percentage at different examination times. Results: Oral treatment with a single PZQ dose of 500 mg/kg in mice infected with cercariae with reduced sensitivity to PZQ revealed a non-significant reduction (35.1%) of total worm burden compared to non-treated control mice. Orally inoculated PZQ- encapsulated niosomes against S. mansoni with reduced sensitivity to PZQ successfully regained the pathogen's sensitivity to PZQ as evidenced by measuring different parameters in comparison to the non-treated infected animals with parasites with reduced sensitivity to PZQ. The mean total worm load was 1.33 ± 0.52 with a statistically significant reduction of 94.09% and complete eradication of male worms. We obtained a remarkable increase in the percentage reduction of tissue egg counts in the liver and intestine (97.68% and 98.56%, respectively) associated with a massive increase in dead eggs and the complete absence of immature stages. Conclusion: PZQ-encapsulated niosomes restored the drug sensitivity against laboratory- induced S. mansoni adult worms with reduced sensitivity to PZQ.

Introducción. El prazicuantel es el único fármaco disponible comercialmente para la esquistosomiasis. La escasez actual de medicamentos alternativos y la falta de medidas preventivas eficaces aumentan su valor. La creciente prevalencia de la resistencia al prazicuantel bajo una presión prolongada del fármaco es, por tanto, un tema emergente. Objetivos. Superar la tolerancia al prazicuantel mediante nanotecnología después de la inducción en laboratorio de un aislamiento de Schistosoma mansoni con sensibilidad reducida al fármaco durante la fase intramolusco. Materiales y métodos. Los caracoles que liberaban cercarias se trataron con prazicuantel en dosis de 200 mg/kg dos veces por semana, seguidas de un intervalo de una semana, y luego se repitieron dos veces de la misma manera. La inducción exitosa de la sensibilidad reducida se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel con respecto a su actividad de natación y el porcentaje de muerte en diferentes momentos de examen. El éxito en inducir una menor sensibilidad se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel. Resultados. El tratamiento oral con una dosis única de prazicuantel de 500 mg/kg en ratones infectados con cercarias con sensibilidad reducida al prazicuantel, reveló una reducción no significativa (35,1 %) de la carga total de gusanos en comparación con los ratones de control no tratados. Los niosomas encapsulados en prazicuantel inoculados por vía oral contra S. mansoni con sensibilidad reducida al prazicuantel, permitieron reestablecer con éxito la sensibilidad del patógeno al medicamento, como lo demostró la medición de diferentes parámetros en comparación con los animales infectados no tratados con parásitos con sensibilidad reducida a prazicuantel. La carga media total de gusanos fue de 1,33 ± 0,52, con una reducción estadísticamente significativa del 94,09 %, y la erradicación completa de los gusanos machos adultos. Se obtuvo un aumento notable en el porcentaje de reducción del recuento de huevos en el tejido del hígado y el intestino (97,68 % y 98,56 %, respectivamente), asociado con un aumento masivo de huevos muertos y ausencia total de estadios inmaduros. Conclusión. Los niosomas encapsulados en prazicuantel restauraron la sensibilidad al fármaco contra gusanos adultos de S. mansoni con sensibilidad reducida al prazicuantel inducida en el laboratorio.

Function of gold nanoparticles in oral cancer beyond drug delivery: Implications in cell apoptosis.

OBJECTIVES: Gold nanoparticles (AuNPs) are used to deliver drugs and therapeutic small molecule inhibitors to cancer cells. Evidence shows that AuNPs coated with nuclear localization sequence can cross the nuclear membrane and induce cellular apoptosis. To determine the therapeutic role of AuNPs, we compared two nanoconstructs conjugated to doxorubicin (DOX) through pH-sensitive and pH-resistant linkers. MATERIALS AND METHODS: We tested DOX nanoconjugates' cytotoxicity, cellular and nuclear uptake in oral squamous cell carcinoma cell line. Furthermore, we evaluated the therapeutic effect of pH-sensitive and pH-resistant DOX bioconjugates in hamster buccal pouch carcinoma model. RESULTS: Our data indicate that pH-resistant and pH-sensitive DOX-nanoconjugates were equally localized in cancer cells, but the pH-resistant DOX nanoparticles were more localized in the nuclei inducing a 2-fold increase in the apoptotic effect compared with the pH-sensitive DOX nanoparticles. Our in vivo results show significantly higher tumor shrinkage and survival rates in animals treated with DOX pH-resistant AuNPs compared with pH-sensitive ones. CONCLUSION: Our findings suggest that AuNPs enhance the cytotoxic effect against cancer cells in addition to acting as drug carriers. DOX pH-resistant AuNPs enhanced accumulation of AuNPs in cancer cells' nuclei inducing a significant cellular apoptosis which was confirmed using in vitro and in vivo experiments without deleterious effects on blood cell count.

Impact of citrate- and chitosan-capped gold nanoparticles on the liver of Swiss albino mice: Histological and cyto-genotoxic study.

The present study aimed to disclose the histological alterations and cyto-genotoxic potential induced by citrate- and chitosan-capped AuNPs on liver of adult Swiss albino mice. Animals were randomly divided into 8 groups. The first two groups were intraperitoneally (i.p) injected with physiological saline once and left for 10 days and every other day for 21 days, respectively, and kept as negative control groups. While the third and fourth groups were injected i.p with a single dose of 2 mg/kg of citrate- and chitosan-capped AuNPs, respectively, and left for 10 days. The fifth and sixth groups were injected i.p every other day for 21 days with 200 µg/kg of citrate- and chitosan-capped AuNPs, respectively. Animals of the seventh and eighth groups were injected i.p with 50 mg/kg cyclophosphamide once and left for 10 days and with 20 mg/kg cyclophosphamide every other day for 21 days, respectively. The livers of mice were dissected and processed for microscopic examination and for analyzing the expression of inflammation-related genes using RT-PCR. In addition, bone marrow samples were taken to investigate the mitotic index and the chromosomal aberrations. The present study showed various degrees of structural changes in the liver of animals received AuNPs. Such changes were more prominent in animals treated with a single dose of AuNPs, particularly with citrate-capped AuNPs as compared to chitosan-capped AuNPs. Furthermore, genotoxic analysis did not reveal any genotoxicity for AuNPs with both coats. Therefore, chitosan-capped AuNPs were less hepatotoxic than citrate-capped ones. However, it has not been proven that AuNPs are genotoxic by both coats.

Preventive prospective of triclosan and triclosan-liposomal nanoparticles against experimental infection with a cystogenic ME49 strain of Toxoplasma gondii.

The preventative effect of triclosan (TS) and TS liposomal nanoparticles was studied on the early establishment of chronic infection with Toxoplasma gondii (T. gondii). Swiss albino mice were orally infected with 10 cysts of avirulent ME49 strain of T. gondii, and 2 weeks later they were orally treated with dual daily doses of 200mg/kg and 120 mg/kg TS and TS liposomes for 30 days; respectively. Effect of TS and TS liposomes was parasitologically and ultrastructurally evaluated, versus infected non-treated control. Their safety was biochemically assessed. Parasitologically, both TS and TS liposomes induced significant reduction in mice mortality, brain parasite burden and infectivity of cysts obtained from the brains of treated mice. Ultrastructurally, scanning electron microscopy of cysts obtained from infected mice treated with either TS or TS liposomes showed surface irregularities, protrusions and depressions. Transmission electron microscopy revealed disintegration of the cyst wall and vacuolation of the bradyzoites with disintegration of plasma membranes of both cysts and bradyzoites whether treated with TS or TS liposomes. Biochemical study reflected the safety of the TS and TS liposomes. Therefore, TS proved an effective, promising and safe preventive drug against early establishment of chronic toxoplasmosis. Loading TS on liposomes marginally enhanced its efficacy against T. gondii cysts yet allowed its use in a lower dose.

Triclosan and triclosan-loaded liposomal nanoparticles in the treatment of acute experimental toxoplasmosis.

Efficacy of triclosan (TS) and TS-loaded liposomes against the virulent strain of Toxoplasma gondii (T. gondii) was evaluated. Swiss albino mice were intraperitoneally infected with 10(4) tachyzoites of RH HXGPRT(-) strain of T. gondii, then were orally treated with 150 mg/kg TS or 100 mg/kg TS liposomes twice daily for 4 days. Mice mortality, peritoneal and liver parasite burdens, viability, infectivity and ultrastructural changes of peritoneal tachyzoites of infected treated mice were studied, in comparison with those of infected non-treated controls. Drug safety was biochemically assessed by measuring liver enzymes and thyroxin. Both TS and TS liposomes induced significant reduction in mice mortality, parasite burden, viability and infectivity of tachyzoites harvested from infected treated mice. Scanning electron microscopy of treated tachyzoites showed distorted shapes, reduced sizes, irregularities, surface protrusions, erosions and peeling besides apical region distortion. Transmission electron microscopy showed that treated tachyzoites were intracellularly distorted, had cytoplasmic vacuolation, discontinuous plasma membranes, nuclear abnormalities and disrupted internal structures. Besides, in TS liposomes-treated subgroup, most tachyzoites were seen intracellularly with complete disintegration of the parasite plasma and nuclear membranes, with complete destruction of the internal structures. Biochemical safety of TS and TS liposomes was proven. Accordingly, TS can be considered as a promising alternative to the standard therapy for treating acute murine toxoplasmosis. Liposomal formulation of TS enhanced its efficacy and allowed its use in a lower dose.

Electronic noses for monitoring benzene occupational exposure in biological samples of Egyptian workers.

OBJECTIVES: Benzene is commonly emitted in several industries, leading to widespread environmental and occupational exposure hazards. While less toxic solvents have been substituted for benzene, it is still a component of petroleum products and is a trace impurity in industrial products resulting in continued higher occupational exposures in industrial settings in developing countries. MATERIALS AND METHODS: We investigated the potential use of an electronic nose (e-nose) to monitor the headspace volatiles in biological samples from benzene-exposed Egyptian workers and non-exposed controls. The study population comprised 150 non-smoking male workers exposed to benzene and an equal number of matching non-exposed controls. We determined biomarkers of benzene used to estimate exposure and risk including: benzene in exhaled air and blood; and its urinary metabolites such as phenol and muconic acid using gas chromatography technique and a portable e-nose. RESULTS: The average benzene concentration measured in the ambient air of the workplace of all studied industrial settings in Alexandria, Egypt; was 97.56 ± 88.12 µg/m(3) (range: 4.69-260.86 µg/m(3)). Levels of phenol and muconic acid were significantly (p < 0.001) higher in both blood and urine of benzene-exposed workers as compared to non-exposed controls. CONCLUSIONS: The e-nose technology has successfully classified and distinguished benzene-exposed workers from non-exposed controls for all measured samples of blood, urine and the exhaled air with a very high degree of precision. Thus, it will be a very useful tool for the low-cost mass screening and early detection of health hazards associated with the exposure to benzene in the industry.