Search results for: tumor necrosis factor-alpha

Authors: Himanshu Rohela

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BACKGROUND: Ewing sarcoma can arise in either bone or soft tissue. Extraskeletal Ewing sarcoma (EES) is an uncommon primary tumor of the soft tissues, accounting for 20 30% of all reported cases of ES. AIM: Was to investigate demographic distribution, survival analysis and factors affecting the survival and recurrence in patients of EES. METHODS: Retrospective study of 19 biopsy-proven EES was performed. Overall survival (OS) using log-rank test and factors affecting OS and local recurrence (LR) were evaluated for the entire cohort. RESULTS: Patients with EES had a mean age of 19.5 and it was more commonly seen in males (63%). Axial location (58%) and solitary presentation (84%) were more common. The average size was 11 cm, 3 of 19 were metastatic at presentation, with the lung beings the most common site for metastasis. 17 received NACT, 16 with VAC-IE regimen and 1 underwent a second line with GEM/DOCE regimen. Unplanned surgery was done in 2 of 19. 3 patients received definitive RT and 13 underwent surgical-wide local excision. 2 of 13 showed good response to NACT. 10 patients required readmission out of which 6 patients had chemotherapy-related complications, 2 had surgical site complications and one patient developed secondary AML post-completion of treatment. A total of 4 patients had a recurrence. One had local recurrence alone, one had distant recurrence alone and 2 patients had a distant and local recurrence both. Tumor size >10 cm, axial location, and previous unplanned surgery was associated with higher LR rate. The mean overall survival was 32 months (2.66 years), with higher rates seen in non-metastatic and non-recurrent settings. CONCLUSIONS: Early and accurate diagnosis is the key to the management of EES, with promising results seen via NACT and RO resection regimens. But further studies with larger study groups are needed to standardize the treatment protocol and evaluate its efficacy.

Keywords: Ewings, sarcoma, extraskeletal, chemotherapy

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Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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Authors: Marta E. Hernandez-Caballero, Veronica Borgonio-Cuadra, Antonio Miranda-Duarte, Xochitl Rojas-Toledo, Normand Garcia-Hernandez, Maura Cardenas-Garcia, Teresa Abad-Camacho

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Breast cancer (BC) is the most common tumor in women over the world. DNA methylation is an epigenetic modification critical in CpG sites, aberrant methylation of CpG islands in promoters is a hallmark of cancer. So, gene expression can be regulated by alterations in DNA methylation. In cell lines DACT2 gene reduces the growth and migration of tumor cells by its participation in the suppression of TGFb/SMAD2/3. PHF20L1 is involved in histone acetylation therefore, it regulates transcription. Our aim was to analyze the methylation status of the DACT2 and PHF20L1 promoter regions in tumoral and healthy mammary tissue from women with BC in different progression states. The study included 77 patients from Centro Medico Nacional La Raza in Mexico City. After identifying a CpG island in DACT2 and PHF20L1 promoters, DNA methylation status was analyzed through sodium bisulfite with subsequent amplification using methylation-specific PCR. Results revealed no changes in methylation status of PHF20L1 and cancer stages (II y III) or in comparison to healthy tissues, it was demethylated. DACT2 promoter methylation was no significant between tumoral stages (II, P = 0.37; III, P = 0.17) or with healthy tissue. Previous data reported DACT2 methylated in nasopharyngeal carcinoma but in this study promoter methylation was not observed. PHF20L1 protein contains N-terminal Tudor and C-terminal plant homeodomain domains, it has been suggested that can stabilize DNMT1 regulating DNA methylation, therefore, was associated with poor prognostic in BC. We found no evidence of methylation in patients and controls in PHF20L1 promoter, so its association with BC may have no direct relation with promoter methylation. More studies including other methylation sites in these genes in BC are necessary.

Keywords: bisulfite conversion, breast cancer, DACT2, DNA methylation, PHF20L1, tumoral status

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Authors: Hasan Frookh Jamal

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This is a case of a 36-year-old Bahraini gentleman diagnosed to have Cushing's Syndrome with a large anterior mediastinal mass. He was sent abroad to the Speciality hospital in Jordan, where he underwent diagnostic video-assisted thoracoscopy, partial thymectomy and pericardial fat excision. Histopathology of the mass was reported to be an Atypical carcinoid tumor with a low Ki67 proliferation index of 5%, the mitotic activity of 4 MF/10HPF and pathological stage classification(pTNM): pT1aN1. MRI of the pituitary gland showed an ill-defined non-enhancing focus of about 3mm on the Rt side of the pituitary on coronal images, with a similar but smaller one on the left side, which could be due to enhancing pattern rather than a real lesion as reported. The patient underwent Ga68 Dotate PET/CT scan post-operatively, which showed multiple somatostatin receptor-positive lesions seen within the tail, body and head of the pancreas and positive somatostatin receptor lymph nodes located between the pancreatic head and IVC. There was no uptake detected at the anterior mediastinum nor at the site of thymic mass resection. There was no evidence of any positive somatostatin uptake at the soft tissue or lymph nodes. The patient underwent IPSS, which proved that the source is, in fact, an ectopic source of ACTH secretion. Unfortunately, the patient's serum cortisol remained elevated after surgery and failed to be suppressed by 1 mg ODST and by 2 days LLDST with a high ACTH value. The patient was started on Osilodrostat for treatment of hypercortisolism for the time being and his future treatment plan with Lutetium-177 Dotate therapy vs. bilateral adrenalectomy is to be considered in an MDT meeting.

Keywords: cushing syndrome, neuroendocrine tumur, carcinoid tumor, Thymoma

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Authors: Sadeem Aljamaan, Reem Hariri, Rahaf Alghamdi, Batool Alotaibi, Batool Alsenan, Lama Althunayyan, Areej Alnemer

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The aim of this study is to correlate between radiological findings and histopathological results in regard to the breast imaging-reporting and data system scores, size of breast masses, molecular subtypes and suspicious radiological features, as well as to assess the concordance rate in histological grade between core biopsy and surgical excision among breast cancer patients, followed by analyzing the change of concordance rate in relation to neoadjuvant chemotherapy in a Saudi population. A retrospective review was conducted over 6-year period (2017-2022) on all breast core biopsies of women preceded by radiological investigation. Chi-squared test (χ2) was performed on qualitative data, the Mann-Whitney test for quantitative non-parametric variables, and the Kappa test for grade agreement. A total of 641 cases were included. Ultrasound, mammography, and magnetic resonance imaging demonstrated diagnostic accuracies of 85%, 77.9% and 86.9%; respectively. magnetic resonance imaging manifested the highest sensitivity (72.2%), and the lowest was for ultrasound (61%). Concordance in tumor size with final excisions was best in magnetic resonance imaging, while mammography demonstrated a higher tendency of overestimation (41.9%), and ultrasound showed the highest underestimation (67.7%). The association between basal-like molecular subtypes and the breast imaging-reporting and data system score 5 classifications was statistically significant only for magnetic resonance imaging (p=0.04). Luminal subtypes demonstrated a significantly higher percentage of speculation in mammography. Breast imaging-reporting and data system score 4 manifested a substantial number of benign pathologies in all the 3 modalities. A fair concordance rate (k= 0.212 & 0.379) was demonstrated between excision and the preceding core biopsy grading with and without neoadjuvant therapy, respectively. The results demonstrated a down-grading in cases post-neoadjuvant therapy. In cases who did not receive neoadjuvant therapy, underestimation of tumor grade in biopsy was evident. In summary, magnetic resonance imaging had the highest sensitivity, specificity, positive predictive value and accuracy of both diagnosis and estimation of tumor size. Mammography demonstrated better sensitivity than ultrasound and had the highest negative predictive value, but ultrasound had better specificity, positive predictive value and accuracy. Therefore, the combination of different modalities is advantageous. The concordance rate of core biopsy grading with excision was not impacted by neoadjuvant therapy.

Keywords: breast cancer, mammography, MRI, neoadjuvant, pathology, US

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Authors: M. R. Akbari, M. Sadeghi, R. Faghihi, M. A. Mosleh-Shirazi, A. R. Khorrami-Moghadam

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Proton radiotherapy (PRT) is becoming an established treatment modality for cancer. The localized tumors, the same as undifferentiated thyroid tumors are insufficiently handled by conventional radiotherapy, while protons would propose the prospect of increasing the tumor dose without exceeding the tolerance of the surrounding healthy tissues. In spite of relatively high advantages in giving localized radiation dose to the tumor region, in proton therapy, secondary neutron production can have significant contribution on integral dose and lessen advantages of this modality contrast to conventional radiotherapy techniques. Furthermore, neutrons have high quality factor, therefore, even a small physical dose can cause considerable biological effects. Measuring of this neutron dose is a very critical step in prediction of secondary cancer incidence. It has been found that FLUKA Monte Carlo code simulations have been used to evaluate dose due to secondaries in proton therapy. In this study, first, by validating simulated proton beam range in water phantom with CSDA range from NIST for the studied proton energy range (34-54 MeV), a proton therapy in thyroid gland cancer was simulated using FLUKA code. Secondary neutron dose equivalent of some organs and tissues after the target volume caused by 34 and 54 MeV proton interactions were calculated in order to evaluate secondary cancer incidence. A multilayer cylindrical neck phantom considering all the layers of neck tissues and a proton beam impinging normally on the phantom were also simulated. Trachea (accompanied by Larynx) had the greatest dose equivalent (1.24×10-1 and 1.45 pSv per primary 34 and 54 MeV protons, respectively) among the simulated tissues after the target volume in the neck region.

Keywords: FLUKA code, neutron dose equivalent, proton therapy, thyroid gland

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Authors: V. Veeraprathap, G. S. Harish, G. Narendra Kumar

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Uncontrolled growth of abnormal cells in the lung in the form of tumor can be either benign (non-cancerous) or malignant (cancerous). Patients with Lung Cancer (LC) have an average of five years life span expectancy provided diagnosis, detection and prediction, which reduces many treatment options to risk of invasive surgery increasing survival rate. Computed Tomography (CT), Positron Emission Tomography (PET), and Magnetic Resonance Imaging (MRI) for earlier detection of cancer are common. Gaussian filter along with median filter used for smoothing and noise removal, Histogram Equalization (HE) for image enhancement gives the best results without inviting further opinions. Lung cavities are extracted and the background portion other than two lung cavities is completely removed with right and left lungs segmented separately. Region properties measurements area, perimeter, diameter, centroid and eccentricity measured for the tumor segmented image, while texture is characterized by Gray-Level Co-occurrence Matrix (GLCM) functions, feature extraction provides Region of Interest (ROI) given as input to classifier. Two levels of classifications, K-Nearest Neighbor (KNN) is used for determining patient condition as normal or abnormal, while Artificial Neural Networks (ANN) is used for identifying the cancer stage is employed. Discrete Wavelet Transform (DWT) algorithm is used for the main feature extraction leading to best efficiency. The developed technology finds encouraging results for real time information and on line detection for future research.

Keywords: artificial neural networks, ANN, discrete wavelet transform, DWT, gray-level co-occurrence matrix, GLCM, k-nearest neighbor, KNN, region of interest, ROI

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Authors: Rawan Al-Nemari, Abdulrahman Al-Senaidy, Abdelhabib Semlali

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Background and objectives: The most common cause of death in women worldwide is breast cancer. Regarding all chemotherapy disadvantages and side effects, it’s becoming necessary to identify natural products that target cancer cells with lesser harmful side effects on non-targeted cells and biological environment. Different parts of A. squamosa L., commonly known as custard apple, show varied therapeutic effects. The objective of this study is to investigate in vitro and in vivo, the anti-cancer activity of A. squamosa leaves extract. Methods: The physiological responses using MTT, nucleus staining, and LDH assays were used to evaluate cell survival and proliferation in both ER+ and ER- cells when they were exposed to extract. Monolayer wound repair assay was used to investigate the effect of extracts on cell migration. Apoptotic gene’s expression was investigated by real-time polymerase chain reaction. To study the effect of the extract on the size of tumor, breast cancer induced rats were used. Results: A. squamosa leaves extract showed high anti-proliferative and cytotoxicity effects against different breast cancer cell lines with high concentration, 100 ug/ml. The extracts have reduced the cells wound closure. Polymerase chain reaction revealed downregulation of Bcl-2 and upregulation of Bax. In breast cancer model animal developed in our laboratory, after 4 weeks treatment, treated groups have shown smaller tumor size in comparison with control group (n=4). Conclusion: These results suggest that A. squamosa leaves extract has anti-cancer activity against breast cancer in both in vitro and in vivo, and it may be developed as a potential novel agent to treat breast cancer.

Keywords: apoptosis, breast cancer, migration, proliferation

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Authors: Medet K. Khamitov, Marat M. Ospanov, Vasiliy M. Lozovoy, Zhenis N. Sakuov, Dastan Z. Rustemov

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With a high rectosigmoid transitional zone in children with Hirschsprung’s disease, the upper rectal, sigmoid, left colon arteries are ligated during the pull-through of the descending part of the colon. As a result, the inferior mesenteric artery ceases to participate in the blood supply to the descending part of the colon. As a result, the reduced colon is supplied with blood only by the middle colon artery, which originates from the superior mesenteric artery. Insufficiency of blood supply to the reduced colon is the cause of the development of chronic hypoxia of the intestinal wall or necrosis of the reduced descending colon. Some surgeons prefer to preserve the left colon artery. However, it is possible to stretch the mesentery, which can lead to bowel retraction to anastomotic leaks and stenosis. Chronic hypoxia of the reduced colon, in turn, is the cause of acquired (secondary) aganglionosis. The highest frequency of anastomotic leaks is observed in children older than five years. The purpose is to reduce the risk of complications in the pull-through procedure of the descending part of the colon in patients with Hirschsprung’s disease by ensuring its sufficient mobility and maintaining blood supply to the lower mesenteric artery. Methodology and events. Two children aged 5 and 7 years with Hirschsprung’s disease were operated under the conditions of the hospital in Nur-Sultan. The diagnosis was made using x-ray contrast enema and histological examination. Operational technique. After revision of the left part of the colon and assessment of the architectonics of its blood vessels, parietal mobilization of the affected sigmoid and rectum was performed on laparotomy access, while maintaining the arterial and venous terminal arcades of the sigmoid vessels. Then, the descending branch of the left colon artery was crossed (if there is an insufficient length of the reduced intestine, the left colonic artery itself may also be crossed). This manipulation provides additional mobility of the pull-through descending part of the colon. The resulting "windows" in the mesentery of the reduced intestine were sutured to prevent the development of an internal hernia. Formed a full-blooded, sufficiently long transplant from the transverse loops of the splenic angle and the descending parts of the colon with blood supply from the upper and lower mesenteric artery, freely, without tension, is reduced to the rectal zone with the coloanal anastomosis 1.5 cm above the dentate line. Results. The postoperative period was uneventful. Patients were discharged on the 7th day. The observation was carried out for six months. In no case, there was a bowel retraction, anastomotic leak, anastomotic stenosis, or other complications. Conclusion. The presented technique of mobilization of the colon for the pull-through procedure in a high transitional rectosigmoid zone of Hirschsprung’s disease allows to maintain normal blood supply to the distal part of the colon and to avoid the tension of the colon. The technique allows reducing the risk of anastomotic leak, bowel necrosis, chronic ischemia, to exclude colon retraction and anastomotic stenosis.

Keywords: blood supply, children, colon mobilization, Hirschsprung's disease, pull-through

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Authors: Nasrud Din, Fawad Saeed, Sajid Hussain, Rai Muhammad Dawood Sultan, Premkumar Sellan, Qasim Khan, Wei Lei

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The continuously increasing external quantum efficiencies of Perovskite light-emitting diodes (LEDs) have received significant interest in the scientific community. The need for monitoring and medical diagnostics has experienced a steady growth in recent years, primarily caused by older people and an increasing number of heart attacks, tumors, and cancer disorders among patients. The application of Perovskite near-infrared light-emitting diode (PeNIRLEDs) has exhibited considerable efficacy in bioimaging, particularly in the visualization and examination of blood arteries, blood clots, and tumors. PeNIRLEDs exhibit exciting potential in the field of blood vessel imaging because of their advantageous attributes, including improved depth penetration and less scattering in comparison to visible light. In this study, we synthesized FAPbI₃ Perovskite doped with different concentrations of 5-Aminovaleric acid (5-AVA) 1-6 mg. The incorporation of 5-AVA as a dopant during the FAPbI₃ Perovskite formation influences the FAPbI3 Perovskite’s structural and optical properties, improving its stability, photoluminescence efficiency, and charge transport characteristics. We found a resulting PL emission peak wavelength of 850 nm and bandwidth of 44 nm, along with a calculated quantum yield of 75%. The incorporation of 5-AVA-modified FAPbI₃ Perovskite into LEDs will show promising results, enhancing device efficiency, color purity, and stability. Making it suitable for various medical applications, including subcutaneous deep vein imaging, blood flow visualization, and tumor illumination.

Keywords: perovskite light-emitting diodes, deep vein imaging, blood flow visualization, tumor illumination

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Authors: Ghada Esheba, Ebtisam Aljerayan, Afnan Al-Ghamdi, Atheer Alsharif, Hanan alzahrani

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Background: Primary ovarian neoplasms comprise a heterogeneous group of tumors of three main subtypes: surface epithelial, germ cell, and sex cord-stromal. The wide morphological variation within and between these groups can result in diagnostic difficulties. Gonadal sex cord-stromal tumors (SCST) represent one of the most heterogeneous categories of human neoplasms, because they may contain various combinations of different gonadal sex cord and stromal element. Aim: The aim of this work is to highlight the clinicopathological characteristics of SCST and to assess the value of alpha-inhibin and calretinin in the distinction between SCST and their mimics. Material and methods: This study was carried out on 100 cases using full tissue sections; 70 cases were SCST and 30 cases were histological mimics of SCST. The cases were studied using immunohistochemically using alpha-inhibin. In addition, an ovarian tissue microarray containing 170 benign and malignant ovarian neoplasms was also studied immunohistochemically for calretinin expression. The ovarian microarray included 14 SCST, 59 ovarian serous borderline tumors, 17 mucinous borderline tumors, 10 mucinous adenocarcinomas, 32 endometrioid adenocarcinomas, 34 clear cell carcinomas, and 4 germ cell tumors. Results: 99% of SCST examined using full tissue sections exhibited positive cytoplasmic staining for inhibin. On the contrary, only 7% of the histological mimics (P value < 0.0001). 86% of SCST in the tissue microarray were positive for calretinin with nuclear and/or cytoplasmic staining compared to only 7% of the other tumor types (P value < 0.0001). Conclusions: SCST have characteristic clinicopathological and immunohistochemical features and their recognition is crucial for proper diagnosis and treatment. Alpha-inhibin and calretinin are of great help in the diagnosis of sex cord-stromal tumors.

Keywords: calretinin, granulosa cell tumor, inhibin, sex cord-stromal tumors

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Authors: Violina Angelova, Huu Q. Lee

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A field study was conducted to evaluate the efficacy of Vetiver (Chrysopogon zizanioides L.) for phytoremediation of contaminated soils. The experiment was performed on agricultural fields contaminated by the Non-Ferrous-Metal Works near Plovdiv, Bulgaria. The experimental plots were situated at different distances (0.5, 3.5, and 15 km) from the source of pollution. The concentrations of Pb, Zn, and Cd in vetiver (roots and leaves) were determined. Correlations between the content of the heavy metal mobile forms extracted with DTPA and their content in the roots and leaves of the Vetiver have been established. The Vetiver is tolerant to heavy metals and can be grown on soils contaminated with heavy metals. Plants are characterized by low ability to absorb and accumulate Pb, Cd, and Zn and have no signs of toxicity (chlorosis and necrosis) at 36.8 mg/kg Cd, 1158.8 mg/kg Pb and 1526.2 mg/kg Zn in the soil. Vetiver plants can be classified as Pb, Cd and Zn excluder, therefore, this plant has the suitable potential for the phytostabilization of heavy metal contaminated soils. Acknowledgements: The authors gratefully acknowledge the financial support by the Bulgarian National Science Fund (Project DFNI 04/9).

Keywords: contaminated soils, heavy metals, phytoremediation, vetiver

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Authors: Deepak Mohan, Sushma Sharma

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Diclofenac sodium, a member of the acetic acid family of non-steroidal anti-inflammatory drugs, is used to retard inflammation, arthritis pain and ankylosing spondylitis. The drug is known to cause severe injury in different tissues due to formation of reactive oxygen species. The present study is focused on the effect of different doses of diclofenac (4 mg/kg/body weight and 14 mg/kg/body weight on histoarchitecture of the liver from 7-28 days of the investigation. Diclofenac administration resulted in distorted hepatic degeneration and formation of wide areas in the form of sinusoidal gaps. Hepatic fibrosis noticed in different stages of investigation could be attributed to chronic inflammation and reactive oxygen species which results in deposition of extracellular matrix proteins. The abrupt degenerative changes observed during later stages of the experiment showed maximum damage to the liver, and there was enlargement of sinusoidal gaps accompanied by maximum necrosis in the tissues.

Keywords: arthritis, diclofenac, histoarchitecture, sinusoidal

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Authors: Warda Jabeen, Romaisa Shamim Khan, Osama Shakeel, Ahmed Faraz Bhatti, Raza Hussain

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Background: The worldwide incidence of cutaneous melanoma (CM) has been on the rise over the past few decades. Primary prevention and early treatment remain the focus of management to reduce the burden of disease. This entails identification of risk factors to prompt early diagnosis. In Pakistan, there is a scarcity of clinico-pathological data relating to cutaneous malignant melanoma. Objective: The purpose of this study was to analyze the epidemiological and clinical characteristics of patients presenting with cutaneous malignant melanoma in Pakistan, and to compare the results with other studies. Method: Shaukat Khanum Memorial Cancer Hospital and Research Centre is currently the only dedicated cancer hospital in the country, accepting patients from all over Pakistan. Majority of the patients, however, belong to the northern half of the country. From the recorded data of the hospital, all cutaneous melanoma cases were identified and evaluated. Results: Between 1997 and 2017, a total of 169 cutaneous melanoma patients were registered at Shaukat Khanum. Mean age was 47.5 years. The highest incidence of melanoma was seen in the age group 40-59 years (n=69, 40.8%). Most commonly reported clinical subtype was unspecified melanoma (n=154, 91%). Amongst those in which T stage was reported, the most frequently observed T-stage at presentation was T4 (n=23, 13.6%). With regards to body distribution, in our study CM was seen most commonly in the lower limb including the hip. The yearly incidence of melanoma has increased/remained stable from 2007 to 2017. Conclusion: cutaneous malignant melanoma is a fairly common disease in Pakistan. Patients tend to present at a more advanced stage as compared to patients in developed countries. Identification of risk factors and tumor characteristics is therefore of paramount importance to deal with these patients.

Keywords: epidemiology of cutaneous malignant melanoma, cutaneous malignant melanoma, Pakistan, skin cancer

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Authors: Luciano Tarantino

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Gas gangrene is a rare, severe infection with a very high mortality rate caused by Clostridium species. The infection causes a non-suppurative localized producing gas lesion from which harmful toxins that impair the inflammatory response cause vessel damage and multiple organ failure. Gas gangrene of the liver is very rare and develops suddenly, often as a complication of abdominal surgery and liver transplantation. The present paper deals with a case of gas gangrene of the liver that occurred after percutaneous MW ablation of hepatocellular carcinoma, resulting in progressive liver necrosis and multi-organ failure in spite of specific antibiotics administration. The patient was successfully treated with percutaneous Radiofrequency ablation. Case report: Female, 76 years old, Child A class cirrhosis, treated with synchronous insertion of 3 MW antennae for large HCC (5.5 cm) in the VIII segment. 24 hours after treatment, the patient was asymptomatic and left the hospital . 2 days later, she complained of fever, weakness, abdominal swelling, and pain. Abdominal US detected a 2.3 cm in size gas-containing area, eccentric within the large (7 cm) ablated area. The patient was promptly hospitalized with the diagnosis of anaerobic liver abscess and started antibiotic therapy with Imipenem/cilastatine+metronidazole+teicoplanine. On the fourth day, the patient was moved to the ICU because of dyspnea, congestive heart failure, atrial fibrillation, right pleural effusion, ascites, and renal failure. Blood tests demonstrated severe leukopenia and neutropenia, anemia, increased creatinine and blood nitrogen, high-level FDP, and high INR. Blood cultures were negative. At US, unenhanced CT, and CEUS, a progressive enlargement of the infected liver lesion was observed. Percutaneous drainage was attempted, but only drops of non-suppurative brownish material could be obtained. Pleural and peritoneal drainages gave serosanguineous muddy fluid. The Surgeon and the Anesthesiologist excluded any indication of surgical resection because of the high perioperative mortality risk. Therefore, we asked for the informed consent of the patient and her relatives to treat the gangrenous liver lesion by percutaneous Ablation. Under conscious sedation, percutaneous RFA of GG was performed by double insertion of 3 cool-tip needles (Covidien LDT, USA ) into the infected area. The procedure was well tolerated by the patient. A dramatic improvement in the patient's condition was observed in the subsequent 24 hours and thereafter. Fever and dyspnea disappeared. Normalization of blood tests, including creatinine, was observed within 4 days. Heart performance improved, 10 days after the RFA the patient left the hospital and was followed-up with weekly as an outpatient for 2 months and every two months thereafter. At 18 months follow-up, the patient is well compensated (Child-Pugh class B7), without any peritoneal or pleural effusion and without any HCC recurrence at imaging (US every 3 months, CT every 6 months). Percutaneous RFA could be a valuable therapy of focal GG of the liver in patients non-responder to antibiotics and when surgery and liver transplantation are not feasible. A fast and early indication is needed in case of rapid worsening of patient's conditions.

Keywords: liver tumor ablation, interventional ultrasound, liver infection, gas gangrene, radiofrequency ablation

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Authors: Walid Ibrahim, Abdul Kasem, Sudeendra Doddi, Ilaria Giono, Tareq Sabagh, Muhammad Ammar, Nermin Osman

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Background: wire-guided localization (WL) is the most widely used method for the localization of non-palpable breast lesions. SAVI SCOUT occult lesion localization (SSL) is a new technique in breast-conservative surgery. SSL has the potential benefit of improving radiology workflow as well as accurate localization. Purpose: The purpose of this study is to compare the breast tissue specimen volume and weight and margin excision between WL and SSL. Materials and methods: A single institution retrospective analysis of 377 female patients who underwent wide local breast excision with SAVI SCOUT and or wire-guided technique between 2018 and 2021 in a UK University teaching hospital. Breast department. Breast tissue specimen volume and weight, and margin excision have been evaluated in the three groups of different localization. Results: Three hundred and seventy-seven patients were studied. Of these, 261 had wire localization, 88 had SCOUT and 28 had dual localization techniques. Tumor size ranged from 1 to 75mm (Median 20mm). The pathology specimen weight ranged from 1 to 466gm (Median 46.8) and the volume ranged from 1.305 to 1560cm³ (Median 106.32 cm³). SCOUT localization was associated with a significantly low specimen weight than wire or the dual technique localization (Median 41gm vs 47.3gm and 47gm, p = 0.029). SCOUT was not associated with better specimen volume with a borderline significance in comparison to wire and combined techniques (Median 108cm³ vs 105cm³ and 105cm³, p = 0.047). There was a significant correlation between tumor size and pathology specimen weight in the three groups. SCOUT showed a better >2mm safety margin in comparison to the other 2 techniques (p = 0.031). Conclusion: Preoperative SCOUT localization is associated with better specimen weight and better specimen margin. SCOUT did not show any benefits in terms of specimen volume which may be due to difficulty in getting the accurate specimen volume due to the irregularity of the soft tissue specimen.

Keywords: scout, wire, localization, breast

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Authors: Amna B. Medani, M. A. Elbadwi Samia, Hassan A. Khalid

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In our study, nine Nubian goat kids were obtained, allotted into three groups, and healthily adapted in pens within the premises of the Veterinary Teaching Hospital, University of Khartoum to be given the oral doses of the dried herb shoots at daily doses of 1 and 5 gm/kg/day with drinking water, while the kids of the control group were left undosed. All goats were slaughtered,if not died, after 35 days. S. argel at the given doses caused signs of arched posture, ruffled hair, shivering and paralysis of limbs. On post mortem, lesions were seen to be hepatic fatty changes, renal necrosis, congested lungs and inflamed intestines. Serum chemistry investigations revealed significant increase (P< 0.05-0.01) in the activities of ALP(alkaline phosphates) and AST( aspartate-aminotransferase) in goats dosed with 5 gm /kg/ day. Also observed were significant increases in inorganic phosphorus and urea concentrations (P < 0.05-0.01) in both dosed goat groups. .Other investigations including the activity of GGT( gamma glutamyltransferase), creatinine, calcium, total protein and albumin illustrated no significant difference from that of the undosed controls. On haematological evaluation , the goat kids dosed with 5 gm/kg/dayshowed a decrease in haemoglobin concentration and red blood cells count of (P < 0.05-0.01).Both groups of dosed goats showed a higher packed cell volume values of (P < 0.05) when compared to the control goats .Mean corpuscular haemoglobin values were not different from those of the control kids. S. argel at the given doses caused signs of arched posture, ruffled hair, shivering and paralysis of limbs. On post mortem, lesions were seen to be hepatic fatty changes, renal necrosis, congested lungs and inflamed intestines. Serum chemistry investigations revealed significant increase (P < 0.05-0.01) in the activities of ALP(alkaline phosphates) and AST( aspartate-aminotransferase) in goats dosed with 5 gm /kg/ day. Also observed were significant increases in inorganic phosphorus and urea concentrations (P < 0.05-0.01) in both dosed goat groups. .Other investigations including the activity of GGT( gamma-glutamyltransferase), creatinine, calcium, total protein and albumin illustrated no significant difference from that of the undosed controls. calcium, total protein and albumin illustrated no significant difference from that of the undosed controls. On haematological evaluation , the goat kids dosed with 5 gm/kg/dayshowed a decrease in haemoglobin concentration and red blood cells count of (P < 0.05-0.01).Both groups of dosed goats showed a higher packed cell volume values of (P < 0.05) when compared to the control goats .Mean corpuscular haemoglobin values were not different from those of the control kids. Data obtained were then discussed to find S. argel irritable to intestines , toxic to the kidney and liver and a haematological mild toxin.Suggestions for future were forwarded.

Keywords: hargal, nubian goats, solenstemma argel, toxicity

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Authors: Vincent Murray

Abstract:

The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.

Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing

Procedia PDF Downloads 121

Authors: Aghaei Amirkhizi Navideh, Sadjadi Soodeh Sadat, Moghaddam Banaem Leila, Athari Allaf Mitra, Johari Daha Fariba

Abstract:

Dendrimers are good candidates for preparing metal nanoparticles because they can structurally and chemically well-defined templates and robust stabilizers. Poly amidoamine (PAMAM) dendrimer-based multifunctional cancer therapeutic conjugates have been designed and synthesized in pharmaceutical industry. In addition, encapsulated nanoparticle surfaces are accessible to substrates so that catalytic reactions can be carried out. For preparation of dendimer-metal nanocomposite, a dendrimer solution containing an average of 55 Yb+3 ions per dendrimer was prepared. Prior to reduction, the pH of this solution was adjusted to 7.5 using NaOH. NaBH4 was used to reduce the dendrimer-encapsulated Yb+3 to the zerovalent metal. The pH of the resulting solution was then adjusted to 3, using HClO4, to decompose excess BH4-. The UV-Vis absorption spectra of the mixture were recorded to ensure the formation of Yb-G5-NH2 complex. High-resolution electron microscopy (HRTEM) and size distribution results provide additional information about dendimer-metal nanocomposite shape, size, and size distribution of the particles. The resulting mixture was irradiated in Tehran Research Reactor 2h and neutron fluxes were 3×1011 n/cm2.Sec and the specific activity was 7MBq. Radiochemical and chemical and radionuclide quality control testes were carried. Gamma Spectroscopy and High-performance Liquid Chromatography HPLC, Thin-Layer Chromatography TLC were recorded. The injection of resulting solution to solid tumor in mice shows that it could be resized the tumor. The studies about solid tumors and nano composites show that ytterbium encapsulated-dendrimer radiopharmaceutical could be introduced as a new therapeutic for the treatment of solid tumors.

Keywords: nano-radio pharmaceutical, ytterbium, PAMAM, dendrimers

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Authors: Navid Mosallaei, Mahmoud Reza Jaafari, Mohammad Yahya Hanafi-Bojd, Shiva Golmohammadzadeh, Bizhan Malaekeh-Nikouei

Abstract:

Background: Docetaxel (DTX), a potent anticancer drug derived from the European yew tree, is effective against various human cancers by inhibiting microtubule depolymerization. Solid lipid nanoparticles (SLNs) have gained attention as drug carriers for enhancing drug effectiveness and safety. SLNs, submicron-sized lipid-based particles, can passively target tumors through the "enhanced permeability and retention" (EPR) effect, providing stability, drug protection, and controlled release while being biocompatible. Methods: The SLN formulation included biodegradable lipids (Compritol and Precirol), hydrogenated soy phosphatidylcholine (H-SPC) as a lipophilic co-surfactant, and Poloxamer 188 as a non-ionic polymeric stabilizer. Two SLN preparation techniques, probe sonication and microemulsion, were assessed. Characterization encompassed SLNs' morphology, particle size, zeta potential, matrix, and encapsulation efficacy. In-vitro cytotoxicity and cellular uptake studies were conducted using mouse colorectal (C-26) and human malignant melanoma (A-375) cell lines, comparing SLN-DTX with Taxotere®. In-vivo studies evaluated tumor inhibitory efficacy and survival in mice with colorectal (C-26) tumors, comparing SLNDTX withTaxotere®. Results: SLN-DTX demonstrated stability, with an average size of 180 nm and a low polydispersity index (PDI) of 0.2 and encapsulation efficacy of 98.0 ± 0.1%. Differential scanning calorimetry (DSC) suggested amorphous encapsulation of DTX within SLNs. In vitro studies revealed that SLN-DTX exhibited nearly equivalent cytotoxicity to Taxotere®, depending on concentration and exposure time. Cellular uptake studies demonstrated superior intracellular DTX accumulation with SLN-DTX. In a C-26 mouse model, SLN-DTX at 10 mg/kg outperformed Taxotere® at 10 and 20 mg/kg, with no significant differences in body weight changes and a remarkably high survival rate of 60%. Conclusion: This study concludes that SLN-DTX, prepared using the probe sonication, offers stability and enhanced therapeutic effects. It displayed almost same in vitro cytotoxicity to Taxotere® but showed superior cellular uptake. In a mouse model, SLN-DTX effectively inhibited tumor growth, with 10 mg/kg outperforming even 20 mg/kg of Taxotere®, without adverse body weight changes and with higher survival rates. This suggests that SLN-DTX has the potential to reduce adverse effects while maintaining or enhancing docetaxel's therapeutic profile, making it a promising drug delivery strategy suitable for industrialization.

Keywords: docetaxel, Taxotere®, solid lipid nanoparticles, enhanced permeability and retention effect, drug delivery, cancer chemotherapy, cytotoxicity, cellular uptake, tumor inhibition

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Authors: Maksim Barsakov

Abstract:

Introduction. In modern plastic surgery, there are a large number of breast lift techniques.Due to the spreading information about the "side effects" of silicone implants, interest in implant-free mastopexy is increasing year after year. However, despite the variety of techniques, patients sometimes do not get full satisfaction from the results of mastopexy because of the unexpressed filling of the upper pole, extended anchoring postoperative scars and sometimes because of obtaining an aesthetically unattractive breast shape. The stability of the result after mastopexy depends on many factors, including postoperative rehabilitation. Stability of weight and hormonal background, stretchability of tissues. The high recurrence rate of ptosis and short-term aesthetic effect of mastopexy indicate the urgency of improving surgical techniques and increasing the stabilization of breast tissue. Purpose of the study. To develop and introduce into practice a technique of mastopexy based on the use of a modified Ribeiro flap, as well as elements of tissue movement and fixation designed to increase the stability of postoperative mastopexy. In addition, to give indications for the application of this surgical technique. Materials and Methods. it operated on 103 patients aged 18 to 53 years from 2019 to 2023 according to the reported method. These were patients with primary mastopexy, secondary mastopexy, and also patient with implant removal and one-stage mastopexy. The patients were followed up for 12 months to assess the stability of the result. Results and their discussion. Observing the patients, we noted greater stability of the breast shape and upper pole filling compared to the conventional classical methods. We did not have to resort to anchoring scars. In 90 percent of cases, a inverted T-shape scar was used. In 10 percent, the J-scar was used. The quantitative distribution of complications identified among the operated patients is as follows: worsened healing of the junction of vertical and horizontal sutures at the period of 1-1.5 months after surgery - 15 patients; at treatment with ointment method healing was observed in 7-30 days; permanent loss of NAC sensitivity - 0 patients; vascular disorders in the area of NAC/areola necrosis - 0 patients; marginal necrosis of the areola-2 patients. independent healing within 3-4 weeks without aesthetic defects. Aesthetically unacceptable mature scars-3 patients; partial liponecrosis of the autoflap unilaterally - 1 patient. recurrence of ptosis - 1 patient (after weight loss of 12 kg). In the late postoperative period, 2 patients became pregnant, gave birth, and no lactation problems were observed. Conclusion. Thus, in the world of plastic surgery methods of breast lift continue to improve, which is especially relevant in modern times, due to the increased attention to this operation. The author's proposed method of mastopexy with glandular autoflap allows obtaining in most cases a stable result, a fuller breast shape, avoiding the presence of extended anchoring scars, and also preserves the possibility of lactation. The author of this article has obtained a patent for invention for this method of mastopexy.

Keywords: mastopexy, mammoplasty, autoflap, personal technique

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Authors: Fatemeh Zeinali Sehrig

Abstract:

Background: miRNAs play an important role in the post-transcriptional regulation of genes, including genes involved in DNA methylation (DNMTs), and are also important regulators of oncogenic pathways. The study of microRNAs and DNMTs in breast cancer allows the development of targeted treatments and early detection of this cancer. Methods and Materials: Clinical Patients and Samples: Institutional guidelines, including ethical approval and informed consent, were followed by the Ethics Committee (Ethics code: IR.IAU.TABRIZ.REC.1401.063) of Tabriz Azad University, Tabriz, Iran. In this study, tissues of 100 patients with breast cancer and tissues of 100 healthy women were collected from Noor Nejat Hospital in Tabriz. The basic characteristics of the patients with breast cancer included: 1)Tumor grade(Grade 3 = 5%, Grade 2 = 87.5%, Grade 1 = 7.5%), 2)Lymph node(Yes = 87.5%, No = 12.5%), 3)Family cancer history(Yes = 47.5%, No = 41.3%, Unknown = 11.2%), 4) Abortion history(Yes = 36.2%).In silico methods (data gathering, process, and build networks): Gene Expression Omnibus (GEO), a high-throughput genomic database, was queried for miRNAs expression profiles in breast cancer. For Experimental protocol Tissue Processing, Total RNA isolation, complementary DNA(cDNA) synthesis, and quantitative real time PCR (QRT-PCR) analysis were performed. Results: In the present study, we found significant (p.value<0.05) changes in the expression level of miRNAs and DNMTs in patients with breast cancer. In bioinformatics studies, the GEO microarray data set, similar to qPCR results, showed a decreased expression of miRNAs and increased expression of DNMTs in breast cancer. Conclusion: According to the results of the present study, which showed a decrease in the expression of miRNAs and DNMTs in breast cancer, it can be said that these genes can be used as important diagnostic and therapeutic biomarkers in breast cancer.

Keywords: gene expression omnibus, microarray dataset, breast cancer, miRNA, DNMT (DNA methyltransferases)

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Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

Abstract:

The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

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Authors: Nendouvhada Livhuwani Portia, Nicole Sibuyi, Kwazikwakhe Gabuza, Adewale Fadaka

Abstract:

Metabolic dysfunction-associated liver disease (MASLD) is a chronic condition characterized by excessive fat accumulation in the liver, distinct from conditions caused by alcohol, viral hepatitis, or medications. MASLD is often linked with metabolic syndrome, including obesity, diabetes, hyperlipidemia, and hypertriglyceridemia. This disease can progress to metabolic dysfunction-associated steatohepatitis (MASH), marked by liver inflammation and scarring, potentially leading to cirrhosis. However, only 43-44% of patients with steatosis develop MASH, and 7-30% of those with MASH progress to cirrhosis. The exact mechanisms underlying MASLD and its progression remain unclear, and there are currently no specific therapeutic strategies for MASLD/MASH. While anti-obesity and anti-diabetic medications can reduce progression, they do not fully treat or reverse the disease. As an alternative, green-synthesized metal nanoparticles (MNPs) are emerging as potential treatments for liver diseases due to their anti-diabetic, anti-inflammatory, and anti-obesity properties with minimal side effects. MNPs like gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have been shown to improve metabolic processes by lowering blood glucose, body fat, and inflammation. The study aimed to explore the effects of green-synthesized MNPs on gene expression in an in vitro model of MASH using C3A/HepG2 liver cells. The MASH model was created by exposing these cells to free fatty acids (FFAs) followed by lipopolysaccharide (LPS) to induce inflammation. Cell viability was assessed with the Water-Soluble Tetrazolium (WST)-1 assay, and lipid accumulation was measured using the Oil Red O (ORO) assay. Additionally, mitochondrial membrane potential was assessed by the tetramethyl rhodamine, methyl ester (TMRE) assay, and inflammation was measured with an Enzyme-Linked Immunosorbent Assay (ELISA). The study synthesized AuNPs from Carpobrotus edulis fruit (CeF) and avocado seed (AvoSE) and AgNPs from Salvia africana-lutea (SAL) using optimized conditions. The MNPs were characterized by UV-Vis spectrophotometry and Dynamic Light Scattering (DLS). The nanoparticles were tested at various concentrations for their impact on the C3A/HepG2-induced MASH model. Among the MNPs tested, AvoSE-AuNPs showed the most promise. They reduced cell proliferation and intracellular lipid content more effectively than CeFE-AuNPs and SAL-AgNPs. Molecular analysis using real-time polymerase chain reaction revealed that AvoSE-AuNPs could potentially reverse MASH effects by reducing the expression of key pro-inflammatory and metabolic genes, including tumor necrosis factor-alpha (TNF-α), Fas cell surface death receptor (FAS), Peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, and Sterol regulatory element-binding protein (SREBPF)-1. Further research is needed to confirm the molecular mechanisms behind the effects of these MNPs and to identify the specific phytochemicals responsible for their synthesis and bioactivities.

Keywords: gold nanoparticles, green nanotechnology, metal nanoparticles, obesity

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Authors: Öznur Saribaş, Si̇bel Kahraman Çeti̇ntaş

Abstract:

It is aimed to compare target volume and critical organ doses by using CyberKnife (CK) in accelerated partial breast irradiation (APBI) in patients with early stage breast cancer. Three different virtual plans were made for Iris, fixed and multi-leaf collimator (MLC) for 5 patients who received radiotherapy in the CyberKnife system. CyberKnife virtual plans were created, with 6 Gy per day totaling 30 Gy. Dosimetric parameters for the three collimators were analyzed according to the restrictions in the NSABP-39/RTOG 0413 protocol. The plans ensured critical organs were protected and GTV received 95 % of the prescribed dose. The prescribed dose was defined by the isodose curve of a minimum of 80. Homogeneity index (HI), conformity index (CI), treatment time (min), monitor unit (MU) and doses taken by critical organs were compared. As a result of the comparison of the plans, a significant difference was found for the duration of treatment, MU. However, no significant difference was found for HI, CI. V30 and V15 values of the ipsi-lateral breast were found in the lowest MLC. There was no significant difference between Dmax values for lung and heart. However, the mean MU and duration of treatment were found in the lowest MLC. As a result, the target volume received the desired dose in each collimator. The contralateral breast and contralateral lung doses were the lowest in the Iris. Fixed collimator was found to be more suitable for cardiac doses. But these values did not make a significant difference. The use of fixed collimators may cause difficulties in clinical applications due to the long treatment time. The choice of collimator in breast SBRT applications with CyberKnife may vary depending on tumor size, proximity to critical organs and tumor localization.

Keywords: APBI, CyberKnife, early stage breast cancer, radiotherapy.

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Authors: Kuan Yin Hsiao, Shyh Ming Kuo, Yi Jhen Wu, Chin Wen Chuang, Chuen-Fu Lin, Wei-qing Yang, Han Hsiang Huang

Abstract:

Anti-tumor effects of natural products, like compounds from marine sponges and soft corals, have been investigated for decades. Polymeric nanoparticles prepared from biodegradable and biocompatible molecules, such as Hyaluronan (HA), Chitosan (CHI) and gelatin have been widely studied. Encapsulation of anti-cancer therapies by the biopolymeric nanoparticles in drug delivery system is potentially capable of improving the therapeutic effects and attenuating their toxicity. In the current study, the anti-bladder cancer effects of heteronemin extracted from the sponge Hippospongia sp. with or without HA and CHI nanoparticle encapsulation were assessed and evaluated in vitro. Results showed that IC50 (half maximal inhibitory concentration) of heteronemin toward T24 human bladder cancer cell viability is approximately 0.18 µg/mL. Both plain and HA nanoparticles-encapsulated heteronemin at 0.2 and 0.4 µg/mL significantly reduced T24 cell viability (P<0.001) while HA nanoparticles-encapsulated heteronemin showed weaker viability-inhibitory effects on L929 fibroblasts compared with plain heteronemin at the identical concentrations. HA and CHI nanoparticles-encapsulated heteronemin exhibited significantly stronger inhibitory effects against migration of T24 human bladder cancer cell than those exerted by plain heteronemin at the same concentrations (P<0.001). The flow cytometric results showed that 0.2 µg/mL HA and CHI nanoparticles-encapsulated heteronemin induced higher early apoptosis rate than that induced by plain heteronemin at the same concentration. These results show that HA and CHI nanoparticle encapsulation is able to elevate anti-migratory and apoptosis-inducing effects exerted by heteronemin against bladder cancer cells in vitro. The in vivo anti-bladder cancer effects of the compound with or without HA/CHI nanoparticle encapsulation will be further investigated and examined using murine tumor models. The data obtained from this study will extensively evaluate of the anti-bladder cancer effects of heteronemin as well as HA/CHI-encapsulated heteronemin and pave a way to develop potential bladder cancer treatment.

Keywords: heteronemin, nanoparticles, hyaluronan, chitosan, bladder cancer

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Authors: Surendra Agrawal, Pravina Gurjar, Supriya Bhide, Ram Gaud

Abstract:

Levamisole hydrochloride is a prominent anticancer drug in the treatment of colon cancer but resulted in toxic effects due poor bioavailability and poor cellular uptake by tumor cells. Levamisole is an unstable drug. Incorporation of this molecule in solid lipids may minimize their exposure to the aqueous environment and partly immobilize the drug molecules within the lipid matrix-both of which may protect the encapsulated drugs against degradation. The objectives of the study were to enhance bioavailability by sustaining drug release and to reduce the toxicities associated with the therapy. Solubility of the drug was determined in different lipids to select the components of Solid Lipid Nanoparticles (SLN). Pseudoternary phase diagrams were created using aqueous titration method. Formulations were subjected to particle size and stability evaluation to select the final test formulations which were characterized for average particle size, zeta potential, and in-vitro drug release and percentage transmittance to optimize the final formulation. SLN of Levamisole hydrochloride was prepared by Nanoprecipitation method. Glyceryl behenate (Compritol 888 ATO) was used as core comprising of Tween 80 as surfactant and Lecithin as co-surfactant in (1:1) ratio. Entrapment efficiency (EE) was found to be 45.89%. Particle size was found in the range of 100-600 nm. Zeta potential of the formulation was -17.0 mV revealing the stability of the product. In-vitro release study showed that 66 % drug released in 24 hours in pH 7.2 which represent that formulation can give controlled action at the intestinal environment. In pH 5.0 it showed 64% release indicating that it can even release drug in acidic environment of tumor cells. In conclusion, results revealed SLN to be a promising approach to sustain the drug release so as to increase bioavailability and cellular uptake of the drug with reduction in toxic effects as dose has been reduced with controlled delivery.

Keywords: SLN, nanoparticulate delivery of levamisole, pharmacy, pharmaceutical sciences

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Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

Abstract:

Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

Abstract:

Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao

Abstract:

To investigate the chemoprotective potential of NBRIQU16 chemotype isolated from Argyreia speciosa (Family: Convolvulaceae) on N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and NaCl-induced gastric carcinomas in Wistar rats. Forty-six male 6-week-old Wistar rats were divided into two groups. Thirty rats in group A were fed with a diet supplemented with 8 % NaCl for 20 weeks and simultaneously given N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in drinking water at a concentration of 100 ug/ml for the first 17 weeks. After administration of the carcinogen, 200 and 400 mg/kg of NBRIQU16 were administered orally once a day throughout the study. From week 18, these rats were given normal water. From week 21, these rats were fed with a normal diet for 15 weeks. Group B containing 16 rats was fed standard diet for thirty-five days. It served as control. Ten rats from group A were sacrificed after 20 weeks. Scarification of remaining animals was conducted after 35 weeks. Entire stomach and some part of the duodenum were incised parallel to the greater curvature, and the samples were collected. After opening the stomach location and size of tumors were recorded. The number of tumors with their locations and sizes were recorded. Expression of survivin was examined by recording the Immunohistochemistry of the specimens. The treatment with NBRIQU16 significantly reduced the nodule incidence and nodule multiplicity in the rats after MNNG administration. Surviving expression in glandular stomachs of normal rats, of rats in middle induction period, in adenocarcinomas and NBRIQU16 treated tissues adjacent to tumor were 0, 42.0 %, 79.3%, and 36.4 %, respectively. Expression of survivin was significantly different as compared to the normal rats. Histological observations of stomach tissues too correlated with the biochemical observations.These finding powerfully supports that NBRIQU16 chemopreventive effect by suppressing the tumor burden and restoring the activities of gastric cancer marker enzymes on MNNG and NaCl-induced gastric carcinomas in Wistar rats.

Keywords: Argyreia speciosa, gastric carcinoma, immunochemistry, NBRIQU16

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