Search results for: Chemotherapy

Authors: F. Bosca, F. Foglietta, F. Turci, E. Calcio Gaudino, S. Mana, F. Dosio, R. Canaparo, L. Serpe, A. Barge

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In recent years, medical science has improved chemotherapy, radiation therapy and adjuvant therapy and has developed newer targeted therapies as well as refining surgical techniques for removing cancer. However, the chances of surviving the disease depend greatly on the type and location of the cancer and the extent of the disease at the start of treatment. Moreover, mainstream forms of cancer treatment have side effects which range from the unpleasant to the fatal. Therefore, the continuation of progress in anti-cancer therapy may depend on placing emphasis on other existing but less thoroughly investigated therapeutic approaches such as Sonodynamic Therapy (SDT). SDT is based on the local activation of a so called 'sonosensitizer', a molecule able to be excited by ultrasound, the radical production as a consequence of its relaxation processes and cell death due to different mechanisms induced by radical production. The present work deals with synthesis, characterization and preliminary in vitro test of Single Walled Carbon Nanotubes (SWCNT) decorated with porphyrins and biological vectors. The SWCNT’s surface was modified exploiting 1, 3-dipolar cycloaddition or Dies Alder reactions. For this purpose, different porphyrins scaffolds were ad-hoc synthesized using also non-conventional techniques. To increase cellular specificity of porphyrin-conjugated SWCNTs and to improve their ability to be suspended in aqueous solution, the modified nano-tubes were grafted with suitable glutamine or hyaluronic acid derivatives. These nano-sized sonosensitizers were characterized by several methodologies and tested in vitro on different cancer cell lines.

Keywords: sonodynamic therapy, porphyrins synthesis and modification, SWNCT grafting, hyaluronic acid, anti-cancer treatment

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Authors: Sarpong Boateng, Rohit Balasundaram, Akua Afrah Amoah

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Introduction: Racial and Gender disparities have been found to be independently associated with Salivary Gland Cancers (SGCs) survival; however, to our best knowledge, there are no previous studies on the interplay of these social determinants on the prognosis of SGCs. The objective of this study was to examine the joint effect of race and gender on the survival of SGCs. Methods: We analyzed survival outcomes of 13,547 histologically confirmed cases of SGCs using the Surveillance Epidemiology and End Results (SEER) database (2004 to 2015). Multivariable Cox regression analysis and Kaplan-Meier curves were used to estimate hazard ratios (HR) after controlling for age, tumor characteristics, treatment type and year of diagnosis. Results: 73.5% of the participants were whites, 8.5% were blacks, 10.1% were Hispanics and 58.5% were males. Overall, males had poorer survival than females (HR = 1.16, p=0.003). In the adjusted multivariable model, there were no significant differences in survival by race. However, the interaction of gender and race was statistically significant (p=0.01) in Hispanic males. Thus, compared to White females (reference), Hispanic females had significantly better survival (HR=0.53), whiles Hispanic males had worse survival outcomes (HR=1.82) for SGCs. Conclusions: Our results show significant interactions between race and gender, with racial disparities varying across the different genders for SGCs survival. This study indicates that racial and gender differences are crucial factors to be considered in the prognostic counseling and management of patients with SGCs. Biologic factors, tumor genetic characteristics, chemotherapy, lifestyle, environmental exposures, and socioeconomic and dietary factors are potential yet proven reasons that could account for racial and gender differences in the survival of SGCs.

Keywords: salivary, cancer, survival, disparity, race, gender, SEER

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Authors: Chutamas Thepmalee, Aussara Panya, Mutita Junking, Jatuporn Sujjitjoon, Nunghathai Sawasdee, Pa-Thai Yenchitsomanus

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Cholangiocarcinoma (CCA) is an aggressive malignancy of bile duct epithelial cells in which the standard treatments, including surgery, radiotherapy, chemotherapy, and targeted therapy are partially effective. Many solid tumors including CCA escape host immune responses by creating tumor microenvironment and generating immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). These cytokines can inhibit dendritic cell (DC) differentiation and function, leading to decreased activation and response of effector CD4+ and CD8+ T cells for cancer cell elimination. To overcome the effects of these immunosuppressive cytokines and to increase ability of DC to activate effector CD4+ and CD8+ T cells, we generated self-differentiated DCs (SD-DCs) with down-regulation of IL-10 and TGF-β receptors for activation of effector CD4+ and CD8+ T cells. Human peripheral blood monocytes were initially transduced with lentiviral particles containing the genes encoding GM-CSF and IL-4 and then secondly transduced with lentiviral particles containing short-hairpin RNAs (shRNAs) to knock-down mRNAs of IL-10 and TGF-β receptors. The generated SD-DCs showed up-regulation of MHC class II (HLA-DR) and co-stimulatory molecules (CD40 and CD86), comparable to those of DCs generated by convention method. Suppression of IL-10 and TGF-β receptors on SD-DCs by specific shRNAs significantly increased levels of IFN-γ and also increased cytolytic activity of DC-activated effector T cells against CCA cell lines (KKU-213 and KKU-100), but it had little effect to immortalized cholangiocytes (MMNK-1). Thus, SD-DCs with down-regulation of IL-10 and TGF-β receptors increased activation of effector T cells, which is a recommended method to improve DC function for the preparation of DC-activated effector T cells for adoptive T-cell therapy.

Keywords: cholangiocarcinoma, IL-10 receptor, self-differentiated dendritic cells, TGF-β receptor

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Authors: Sadaf Kalhori

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Introduction: Doxorubicin (DOX)-induced cardiotoxicity is widely known as the most severe complication of anthracycline-based chemotherapy in patients with cancer. It is unknown whether Deferiprone (DFP), could reduce the severity of DOX-induced cardiotoxicity by inhibiting free radical reactions. Thus, this study was performed to assess the protective effect of Deferiprone on DOX-induced cardiotoxicity in a rat model. Methods: The rats were divided into five groups. Group one was a control group. Group 2 was DOX (2 mg/kg/day, every other day for 12 days), and Group three to five which receiving DOX as in group 2 and DFP 75,100 and 150 mg/kg/day, for 19 days, respectively. DFP was starting 5 days prior to the first DOX injection and two days after the last DOX injection throughout the study. Electrocardiographic and hemodynamic studies, along with histopathological examination, were conducted. In addition, serum sample was taken and total cholesterol, Malone dialdehyde, triglyceride, albumin, AST, ALT, total protein, lactate dehydrogenase, total anti-oxidant and creatine kinase were assessed. Result: Our results showed the normal structure of endocardial, myocardial and pericardial in the control group. Pathologic data such as edema, hyperemia, bleeding, endocarditis, myocarditis and pericarditis, hyaline degeneration, cardiomyocyte necrosis, myofilament degeneration and nuclear chromatin changes were assessed in all groups. In the DOX group, all pathologic data was seen with mean grade of 2±1.25. In the DFP group with a dose of 75 and 100 mg, the mean grade was 1.41± 0.31 and 1±.23, respectively. In DFP group with a dose of 150, the pathologic data showed a milder change in comparison with other groups with e mean grade of 0.45 ±0.19. Most pathologic data in DFP groups showed significant changes in comparison with the DOX group (p < 0.001). Discussion: The results also showed that DFP treatment significantly improved DOX-induced heart damage, structural changes in the myocardium, and ventricular function. Our data confirm that DFP is protective against cardiovascular-related disorders induced by DOX. Clinical studies are needed to be involved to examine these findings in humans.

Keywords: cardiomyopathy, deferiprone, doxorubicin, rat

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Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal

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Doxorubicin, also known as adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemias, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhoea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, anti-inflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilino-ethyl)benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 µM where as for doxorubicin is 7.2 µ.

Keywords: Doxorubicin, auto dock, in silco, in vitro

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Authors: Angel Champion, Sadia Kanwal, Rafat Siddiqui

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Harnessing phytochemicals from plant sources presents a novel opportunity to prevent or treat malignant diseases, including breast cancer. Chemotherapy lacks precision in targeting cancerous cells while sparing normal cells, but a phytopharmaceutical approach may offer a solution. Dandelion, a common weed plant, is rich in phytochemicals and provides a safer, more cost-effective alternative with lower toxicity than traditional pharmaceuticals for conditions such as breast cancer. In this study, an in-vitro experiment will be conducted using the ethanol extract of Dandelion on triple-negative MDA-231 breast cancer cell lines. The polyphenolic analysis revealed that the Dandelion extract, particularly from the root and leaf (both cut and sifted), had the most potent antioxidant properties and exhibited the most potent antioxidation activity from the powdered leaf extract. The extract exhibits prospective promising effects for inducing cell proliferation and apoptosis in breast cancer cells, highlighting its potential for targeted therapeutic interventions. Standardizing methods for Dandelion use is crucial for future clinical applications in cancer treatment. Combining plant-derived compounds with cancer nanotechnology holds the potential for effective strategies in battling malignant diseases. Utilizing liposomes as carriers for phytoconstituent anti-cancer agents offers improved solubility, bioavailability, immunoregulatory effects, advancing anticancer immune function, and reducing toxicity. This integrated approach of natural products and nanotechnology has significant potential to revolutionize healthcare globally, especially in underserved communities where herbal medicine is prevalent.

Keywords: apoptosis, antioxidant activity, cancer nanotechnology, phytopharmaceutical

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Authors: Athicha Cherdpunt, Patompong Satapornpong

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The medical cannabis is made up of components also known as cannabinoids, which consists of two ingredients which are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Interestingly, the Cannabinoid can be used for many treatments such as chemotherapy, including nausea and vomiting, cachexia, anorexia nervosa, spinal cord injury and disease, epilepsy, pain, and many others. However, the adverse drug reactions (ADRs) of THC can cause sedation, anxiety, dizziness, appetite stimulation and impairments in driving and cognitive function. Furthermore, genetic polymorphisms of CYP2C9, CYP2C19 and CYP3A4 influenced the THC metabolism and might be a cause of ADRs. Particularly, CYP2C19*17 allele increases gene transcription and therefore results in ultra-rapid metabolizer phenotype (UM). The aim of this study, is to investigate the frequency of CYP2C19*17 alleles in Thai patients who have been treated with medical cannabis. We prospectively enrolled 60 Thai patients who were treated with medical cannabis and clinical data from College of Pharmacy, Rangsit University. DNA of each patient was isolated from EDTA blood, using the Genomic DNA Mini Kit. CYP2C19*17 genotyping was conducted using the real time-PCR ViiA7 (ABI, Foster City, CA, USA). 30 patients with medical cannabis-induced ADRs group, 20 (67%) were female, and 10 (33%) were male, with an age range of 30-69 years. On the other hand, 30 patients without medical cannabis-induced ADRs (control group) consist of 17 (57%) female and 13 (43%) male. The most ADRs for medical cannabis treatment in the case group were dry mouth and dry throat (77%), tachycardia (70%), nausea (30%) and arrhythmia(10%). Accordingly, the case group carried CYP2C19*1/*1 (normal metabolizer) approximately 93%, while 7% patients carrying CYP2C19*1/*17 (ultra rapid metabolizers) exhibited in this group. Meanwhile, we found 90% of CYP2C19*1/*1 and 10% of CYP2C19*1/*17 in control group. In this study, we identified the frequency of CYP2C19*17 allele in Thai population which will support the pharmacogenetics biomarkers for screening and avoid ADRs of medical cannabis treatment.

Keywords: CYP2C19, allele frequency, ultra rapid metabolizer, medical cannabis

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Authors: G. Wagner, R. Herrmann

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Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular substrates that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively nonpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C, H, N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage.

Keywords: cytotoxicity, mesoporous silica, nanoparticles, platinum compounds

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Authors: Valiollah Babaeipour, Mahdi Rahaie

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food supplements are rich in specific nutrients and bioactive compounds that eliminate free radicals and improve cellular metabolism. The major bioactive compounds are found in bran and cereal sprouts. Secondary metabolites of these microorganisms have antioxidant properties that can be used alone or in combination with chemotherapy and radiation therapy to treat cancer. Biologically active compounds such as benzoquinone derivatives extracted from fermented wheat germ extract (FWGE) have several positive effects on the overall state of human health and strengthen the immune system. The present work describes the discontinuous fermentation of raw wheat germ for FWGE production through the simultaneous culture process using the probiotic strains of Saccharomyces cerevisiae, Lactobacillus plantarum, and the possibility of using solid waste. To increase production efficiency, first to select important factors in the optimization of each fermentation process, using a factorial statistical scheme of stirring fraction (120 to 200 rpm), dilution of solids to solvent (1 to 8-12), fermentation time (16 to 24 hours) and strain to wheat germ ratio (20% to 50%) were studied and then simultaneous culture was performed to increase the yields of 2 and 6 dimethoxybenzoquinone (2,6-DMBQ). Since 2 and 6 dimethoxy benzoquinone were fermented as the main biologically active compound in wheat germ extract, UV-Vis analysis was performed to confirm the presence of 2 and 6 dimethoxy benzoquinone in the final product. In addition, 2,6-DMBQ of some products was isolated in a non-polar C-18 column and quantified using high performance liquid chromatography (HPLC). Based on our findings, it can be concluded that the increase of 2 and 6 dimethoxybenzoquinone in the simultaneous culture of Saccharomyces cerevisiae - Lactobacillus plantarum compared to pure culture of Saccharomyces cerevisiae (from 1.89 mg / g) to 28.9% (2.66 mg / g) Increased.

Keywords: wheat germ, FWGE, saccharomyces cerevisiae, lactobacillus plantarum, co-culture, 2, 6-DMBQ

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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: Akram Boubakri, Fethi Choubani, Tan Hoa Vuong, Jacques David

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Nowadays, microwave hyperthermia is considered as an effective treatment for the malignant tumors. This microwave treatment which comes to substitute the chemotherapy and the surgical intervention enables an in-depth tumor heating without causing any diseases to the sane tissue. This technique requires a high precision system, in order to effectively concentrate the heating just in the tumor, without heating any surrounding healthy tissue. In the hyperthermia treatment, the temperature in cancerous area is typically raised up to over 42◦C and maintained for one hour in order to destroy the tumor sufficiently, whilst in the surrounding healthy tissues, the temperature is maintained below 42◦C to avoid any damage. Metamaterial lenses are widely used in medical applications like microwave hyperthermia treatment. They enabled a subdiffraction resolution thanks to the amplification of the evanescent waves and they can focus electromagnetic waves from a point source to a point image. Metasurfaces have been used to built metamaterial lenses. The main mechanical advantages of those structures over three dimensional material structures are ease of fabrication and a smaller required volume. Here in this work, we proposed a metasurface based lens operating at the frequency of 6 GHz and designed for microwave hyperthermia. This lens was applied and showed good results in focusing and heating the tumor inside a breast tissue with an increased and maintained temperature above 42°C. The tumor was placed in the focal distance of the lens so that only the tumor tissue will be heated. Finally, in this work, it has been shown that the hyperthermia area within the tissue can be carefully adjusted by moving the antennas or by changing the thickness of the metamaterial lenses based on the tumor position. Even though the simulations performed in this work have taken into account an ideal case, some real characteristics can be considered to improve the obtained results in a realistic model.

Keywords: focusing, hyperthermia, metamaterial lenses, metasurface, microwave treatment

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Authors: C. Panebianco, K. Adamberg, S. Adamberg, C. Saracino, M. Jaagura, K. Kolk, A. Di Chio, P. Graziano, R. Vilu, V. Pazienza

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Background/Aims: Despite recent advances in treatment options, a modest impact on the outcome of the pancreatic cancer (PC) is observed so far. Short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. However, diseased people may refuse to follow the fasting regimen and fasting may worsen the weight loss often occurring in cancer patients. Therefore, alternative approaches are needed. The aim of this study was to assess the effect of Engineered Low glycemic food ELGIF mimicking diet on growth of cancer cell lines in vitro and in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods: BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in control and ELGIF mimicking diet culturing condition to evaluate the tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to ELGIF to assess the tumor volume and weight as compared to mice fed with control diet. Results: Pancreatic cancer cells cultured in ELGIF mimicking medium showed decreased levels of proliferation as compared to those cultured in the standard medium. Consistently, xenograft pancreatic cancer mice subjected to ELGIF diet displayed a significant decrease in tumor growth. Conclusion: A positive effect of ELGIF diet on proliferation in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that engineered dietary interventions could be supportive as synergistic approach to enhance the efficacy of existing cancer treatments in pancreatic cancer patients.

Keywords: functional food, microbiota, mouse model, pancreatic cancer

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Authors: Luciano Tarantino, Emanuele Balzano, Paolo Tarantino, Riccardo Aurelio Nasto, Aurelio Nasto

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Liver transplantation (OLT) is contraindicate in Portal Vein tumor Thrombosis (PVTT) from Hepatocellular Carcinoma at hepatic hilum(pH-HCC) Surgery,Thermal ablation and chemotherapy show poorer outcomes Electrochemotherapy (ECT) has been successfully used in patients with pH-HCC with PVTT. We report the results of ECT as downstaging aimed to definitive cure by OLT. F.P. 53 years HBV related Cirrhosis Child-Pugh B7 class; EGDS F2 aesophageal Varices. Diabetes. April 2016 : Enhanced Computed Tomography (CT) detected HCC(n.3 nodules in VII-VIII-VI;diameter range=25 cm) and PVTT of right portal vein. The patient was considered ineligible for OLT. May 2016: first ablation session with percutaneous Radiofrequency-ablation(RFA) of 3 HCC-nodules . August 2016: second ablation session with ECT of PVTT. CT october 2016: disappearance of PVTT and patent right portal vein. No intraparenchymal recurrence. CT march 2017: No recurrence in portal vein and in the left lobe. local recurrence in the VII-VIII segments. May 2017 : transarterial chemoembolization (TACE) of right lobe recurrences. CT October 2017: patent right portal vein. No recurrence. The patient was reconsidered for OLT. He underwent OLT in April 2018. At 36-months follow-up , no intrahepatic recurrence of HCC occurred. March 2021: enhanced CT and PET/CT detected a single small nodule (1.5 cm) uptaking tracer in the left upper pulmonary lobe, no hepatic recurrence . CT-guided FNB showed metastasis from HCC . June 2021: left lung upper lobectomy . At the current time the patient is alive and recurrence-free at 64 months follow-up. ECT Could be aneffective technique as pre-OLT dowstaging in HCC with PVTT.

Keywords: liver tumor ablation, interventional ultrasound, electrochemotherapy, liver transplantation

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Authors: Nejla Fourati, Zied Fessi, Fatma Dhouib, Wicem Siala, Leila Farhat, Afef Khanfir, Wafa Mnejja, Jamel Daoud

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Purpose: Radiation induced hypothyroidism in nasopharyngeal cancer (NPC) ranged from 15% to 55%. In reported data, it is considered as a common late complication of definitive radiation and is mainly observed 2 years after the end of treatment. The aim of this study was to evaluate the incidence of early hypothyroidism within 6 months after radiotherapy. Patients and methods: From June 2017 to February 2020, 35 patients treated with concurrent chemo-radiotherapy (CCR) for NPC were included in this prospective study. Median age was 49 years [23-68] with a sex ratio of 2.88. All patients received intensity modulated radiotherapy (IMRT) at a dose of 69.96 Gy in 33 daily fractions with weekly cisplatin (40mg/m²) chemotherapy. Thyroid stimulating hormone (TSH) and Free Thyroxine 4 (FT4) dosage was performed before the start of radiotherapy and 6 months after. Different dosimetric parameters for the thyroid gland were reported: the volume (cc); the mean dose (Dmean) and the %age of volume receiving more than 45 Gy (V45Gy). Wilcoxon Test was used to compare these different parameters between patients with or without hypothyroidism. Results: At baseline, 5 patients (14.3%) had hypothyroidism and were excluded from the analysis. For the remaining 30 patients, 9 patients (30%) developed a hypothyroidism 6 months after the end of radiotherapy. The median thyroid volume was 10.3 cc [4.6-23]. The median Dmean and V45Gy were 48.3 Gy [43.15-55.4] and 74.8 [38.2-97.9] respectively. No significant difference was noted for all studied parameters. Conclusion: Early hypothyroidism occurring within 6 months after CCR for NPC seems to be a common complication (30%) that should be screened. Good patient monitoring with regular dosage of TSH and FT4 makes it possible to treat hypothyroidism in asymptomatic phase. This would be correlated with an improvement in the quality of life of these patients. The results of our study do not show a correlation between the thyroid doses and the occurrence of hypothyroidism. This is probably related to the high doses received by the thyroid in our series. These findings encourage more optimization to limit thyroid doses and then the risk of radiation-induced hypothyroidism

Keywords: nasopharyngeal carcinoma, hypothyroidism, early complication, thyroid dose

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

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Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

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Authors: Chiou-Fang Liou

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Cancer has been one of the most life-threaten diseases worldwide for 30+ years. The influences of cancer illness include symptoms from cancer itself along with its treatments. The quality of life among patients diagnosed with cancer during cancer treatments has been conceptualized within four domains: Functional Well-Being, Social Well-Being, Physical Well-Being, and Emotional Well-Being. Patients with cancer often need to make adjustments to face all the challenges. The middle-range theory of Resourcefulness and Quality of life has been applied to explore factors contributing to cancer patients’ needs. Resourcefulness is defined as sets of skills that can be learned and consisted of Person and Social Resourcefulness. Empirical evidence also supported a possible relationship between Resourcefulness and Quality of Life. However, little is known about the extent to which the two concepts are related to each other. This study, therefore, applied a multivariate technique, Canonical Correlation Analysis, to identify the relationship between the two sets of variables with multi-dimensional measures, the Resourcefulness and Quality of Life in Cancer patients receiving treatments. After IRB approval, this multi-centered study took place at two medical centers in the Central Region of Taiwan. Sample A total of 186 patients with various cancer diagnoses and either receiving radiation therapy or chemotherapy consented to and answered questionnaires. The Import findings of the Generalized F test identified two typical sets with several linear relations and explained a total of 79.1% of the total variance. The first typical set found Personal Resourcefulness negatively related to Social Well-being, Functional being, Emotional Well-being, and Physical, in that order. The second typical set found Social Resourcefulness negatively related to Functional Well-being and Physical-being yet positively related to Social Well-being and Emotional Well-being. Discussion and Conclusion, The results of this presented study supported the statistically significant relationship between two sets of variables that are consistent with the theory. In addition, the results are considerably important in cancer patients receiving cancer treatments.

Keywords: cancer, canonical correlation analysis, quality of life, resourcefulness

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Authors: Chodidjah, Edi Dharmana, Hardhono, Sarjadi

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Breast cancer treatment options including surgery, radiation therapy, chemotherapy, and immunotherapy have not been effective. Besides, they have side effects. Keladi Tikus (Typhonium flagelliforme) has been shown to improve immune system, suppress tumor growth and induce apoptosis. One of the parameters for immune system, tumor growth and apoptosis is IFNγ (Interferon γ), VEGF (Vascular Endothelial Growth Factor) and Caspase 3 respectively. The aim of this study was to examine the effect of the administration of Keladi Tikus tuber extract at the dose of 200 mg/kgBW, 400 mg/KgBW, and 800 mg/kgBW on the level of IFNγ, VEGF and caspase 3 expression. In this experimental study using post test randomized control group design, 24 CH3 mice with tumor were randomly divided into 4 groups including control group and treated groups: Treated with 0.2 cc extract of Keladi Tikus at the dose of 200 mg/kgBW, 400 mg/kgBW, 800 mg/kgBW, respectively for 30 days. On day 31 the lymphatic tissue was taken and evaluated for its level of IFNγ, using ELISA. The tumor tissue was taken and subjected to immunohistochemistry staining for VEGF and caspase 3 expression evaluation. The data on IFNγ, VEGF and Caspase 3 expression were analyzed using One Way Anova with significant level of 0.05. One Way Anova resulted in p<0.05. LSD test showed that the level of IFNγ and Caspase 3 for control group was different from that of treated groups. There was no significant different between the treated group of 400 mg/KgBW and 800mg/KgBW. VEGF expressions for all the treated groups were significant. In conclusion, the oral administration of ethanolic extract of Keladi Tikus (Typhonium flagelliforme) at the dose of 200mg/kgBW, 400 mg/kgBW,800 mg/kgBW increases IFNγ, Caspase 3 and decreases VEGF expression in C3H mice with adenocarsinoma mamma.

Keywords: Typhonium flagelliforme, IFNγ, caspase 3, VEGF

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Authors: Chukwudalu C. Nwazojie, Wole W. Soboyejo, John Obayemi, Ali Salifu Azeko, Sandra M. Jusu, Chinyerem M. Onyekanne

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The conventional methods for the diagnosis and treatment of breast cancer include bulk systematic mammography, ultrasound, dynamic contrast-enhanced fast 3D gradient-echo (GRE) magnetic resonance imaging (MRI), surgery, chemotherapy, and radiotherapy. However, nanoparticles and drug-loaded polymer microspheres for disease (cancer) targeting and treatment have enormous potential to enhance the approaches that are used today. The goal is to produce an implantable biomedical device for localized breast cancer drug delivery within Africa and the world. The main advantage of localized delivery is that it reduces the amount of drug that is needed to have a therapeutic effect. Polymer blends of poly (D,L-lactide-co-glycolide) (PLGA) and polycaprolactone (PCL), which are biodegradable, is used as a drug excipient. This work focuses on the development of PLGA-PCL (poly (D,L-lactide-co-glycolide) (PLGA) blended with based injectable drug microspheres and are loaded with anticancer drugs (prodigiosin (PG), and paclitaxel (PTX) control) and also the conjugated forms of the drug functionalized with LHRH (luteinizing hormone-releasing hormone) (PG-LHRH, and PTX- LHRH control), using a single-emulsion solvent evaporation technique. The encapsulation was done in the presence of PLGA-PCL (as a polymer matrix) and poly-(vinyl alcohol) (PVA) (as an emulsifier). Comparative study of the various drugs release kinetics and degradation mechanisms of the PLGA-PCL with an encapsulated drug is achieved, and the implication of this study is for the potential application of prodigiosin PLGA-PCL loaded microparticles for controlled delivery of cancer drug and treatment to prevent the regrowth or locoregional recurrence, following surgical resection of triple-negative breast tumor.

Keywords: cancer, polymers, drug kinetics, nanoparticles

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Authors: Atena Sadat Hosseini, Mohammadhossein Habibi

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Acute myeloid leukemia (AML) is the most typically diagnosed leukemia. In older adults, AML imposes a dismal outcome. AML originates with a dominant mutation, then adds collaborative, transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Several chemotherapeutic drugs are used for this cancer. These drugs are naturally associated with several side effects, and finding a more accurate molecular mechanism of these drugs can have a significant impact on the selection and better candidate of drugs for treatment. In this study, we evaluated bortezomibin myeloma cells using bioinformatics analysis and evaluation of RNA-Seq data. Then investigated the molecular pathways proteins- proteins interactions associated with this chemotherapy drug. A total of 658upregulated genes and 548 downregulated genes were sorted.AUF1 (hnRNP D0) binds and destabilizes mRNA, degradation of GLI2 by the proteasome, the role of GTSE1 in G2/M progression after G2 checkpoint, TCF dependent signaling in response to WNT demonstrated in upregulated genes. Besides insulin resistance, AKT phosphorylates targets in the nucleus, cytosine methylation, Longevity regulating pathway, and Signal Transduction of S1P Receptor were related to low expression genes. With respect to this results, HIST2H2AA3, RP11-96O20.4, ZED9, PRDX1, and DOK2, according to node degrees and betweenness elements candidates from upregulated genes. in the opposite side, PYURF, NRSN1, FGF23, UPK3BL, and STAG3 were a prominent role in downregulated genes. Sum up, Using in silico analysis in the present study, we conducted a precise study ofbortezomib molecular mechanisms in myeloma cells. so that we could take further evaluation to discovermolecular cancer therapy. Naturally, more additional experimental and clinical procedures are needed in this survey.

Keywords: myeloma cells, acute myeloid leukemia, bioinformatics analysis, bortezomib

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Authors: Paras Agarwal

Abstract:

Background: Initially believed to be rare, metastases to the eye are the most common ocular malignancy. The choroid’s high perfusion rate not only makes it the most susceptible ocular site for tumour seeding, but also promotes its growth. The cancers most frequently responsible for choroidal metastases originate from the breast and lung, although a significant proportion have unidentified primaries at the time of presentation. Case Presentation: This case report describes a 34 year old female presenting to the ophthalmology department with a one month history of painless distorted vision. On fundus examination, she was noted to have bilateral choroidal lesionsand subsequently underwent a comprehensive diagnostic work-up. The patient was diagnosed with metastatic pulmonary adenocarcinoma, despite lacking conventional risk factors. As she was found to have a mutation in EGFR, the patient was commenced on tyrosine-kinase inhibition with afatinib. The choroidal lesions regressed with a significant improvement in visual acuity and a dramatic anatomical reduction of the choroidal masses. Conclusions: Our case demonstrates the importance of considering metastases as a differential diagnosis for choroidal lesions. Appropriate and thorough history-taking, examination and investigations may be required in order to deduce the underlying cause. Our case is unusual in view of the choroidal lesion being the primary manifestation of metastatic lung cancer in a young patient with no known risk factors. Early recognition of choroidal metastases is important as it is often the first sign of tumour dissemination and will prompt earlier treatment with systemic medications such as chemotherapy, immunotherapy, targeted therapy or hormonal therapy. Our case report also demonstrates the efficacy of afatinib for the treatment of choroidal metastases, with morphological and functional improvements observed with regard to the choroidal metastatic tumour.

Keywords: choroidal neoplasm, choroidal naevus, pulmonary adenocarcinoma, metastases, lung cancer

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Authors: N. Jait, M. Maamar, H. Khibri, H. Harmouche, N. Mouatssim, W. Ammouri, Z. Tazimezaelek, M. Adnaoui

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Introduction: Uveitis presents with inflammation of the uvea, intraocular, of heterogeneous etiology and presentation. The objective of our study is to describe the clinical and therapeutic characteristics of infectious uveitis in HIV+ and HIV- patients. Patients and Methods: This is a retrospective study conducted at the internal medicine department of CHU Ibn Sina in Rabat over a period of 12 years (2010–2021), collecting 42 cases of infectious uveitis. Results: 42 patients were identified. 34% (14 cases) had acquired immunosuppression (9 cases: 22% had HIV infection and 12% were on chemotherapy), and 66% were immunocompetent. The M/F sex ratio was 1.1. The average age was 39 years old. Uveitis revealed HIV in a single case; 8/9 patients have already been followed, their average viral load is 3.4 log and an average CD4 count is 356/mm³. The revealing functional signs were: ocular redness (27%), decreased visual acuity (63%), visual blurring (40%), ocular pain (18%), scotoma (13%), and headaches (4%). The uveitis was site: anterior (30%), intermediate (6%), posterior (32%), and pan-uveitis (32%); unilateral in 80% of patients and bilateral in 20%. The etiologies of uveitis in HIV+ were: 3 cases of CMV, 2 cases of toxoplasmosis, 1 case of tuberculosis, 1 case of HSV, 1 case of VZV, and 1 case of syphilis. Etiologies of immunocompetent patients: tuberculosis (41%), toxoplasmosis (18%), syphilis (15%), CMV infection (4 cases: 10%), HSV infection (4 cases: 10%) , lepromatous uveitis (1 case: 2%), VZV infection (1 case: 2%), a locoregional infectious cause such as dental abscess (1 case: 2%), and one case of borreliosis (3% ). 50% of tuberculous uveitis was of the pan-uveitis type, 75% of the uveitis by toxoplasmosis was of the posterior type. Uveitis was associated with other pathologies in 2 seropositive cases (cerebral vasculitis, multifocal tuberculosis). A specific treatment was prescribed in all patients. The initial evolution was favorable in 67%, including 12% HIV+. 11% presented relapses of the same seat during uveitis of the toxoplasmic, tuberculous and herpetic type. 47% presented complications, of which 4 patients were HIV+: 3 retinal detachments; 7 Retinal hemorrhages. 6 unilateral blindness (including 2 HIV+ patients). Conclusion: In our series, the etiologies of infectious uveitis differ between HIV+ and HIV- patients. In HIV+ patients most often had toxoplasmosis and CMV, while HIV - patients mainly presented with tuberculosis and toxoplasmosis. The association between HIV and uveitis is undetermined, but HIV infection was an independent risk factor for uveitis.

Keywords: uveitis, HIV, immunosuppression, infection

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Authors: Ahmed Atwa, Ashraf Hafez, Mohamed Abdelhameed, Adel Nabeeh, Mohamed Dawaba, Tamer Helmy

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Introduction and Objective: Tumour staging and grading do not usually reflect the future behavior of Wilms' tumor (WT) regarding mortality. Therefore, in this study, P53, Ki67 and cyclin A immunohistochemistry were used in a trial to predict WT cancer-specific survival (CSS). Methods: In this nonconcurrent cohort study, patients' archived data, including age at presentation, gender, history, clinical examination and radiological investigations, were retrieved then the patients were reviewed at the outpatient clinic of a tertiary care center by history-taking, clinical examination and radiological investigations to detect the oncological outcome. Cases that received preoperative chemotherapy or died due to causes other than WT were excluded. Formalin-fixed, paraffin-embedded specimens obtained from the previously preserved blocks at the pathology laboratory were taken on positively charged slides for IHC with p53, Ki67 and cyclin A. All specimens were examined by an experienced histopathologist devoted to the urological practice and blinded to the patient's clinical findings. P53 and cyclin A staining were scored as 0 (no nuclear staining),1 (<10% nuclear staining), 2 (10-50% nuclear staining) and 3 (>50% nuclear staining). Ki67 proliferation index (PI) was graded as low, borderline and high. Results: Of the 75 cases, 40 (53.3%) were males and 35 (46.7%) were females, and the median age was 36 months (2-216). With a mean follow-up of 78.6±31 months, cancer-specific mortality (CSM) occurred in 15 (20%) and 11 (14.7%) patients, respectively. Kaplan-Meier curve was used for survival analysis, and groups were compared using the Log-rank test. Multivariate logistic regression and Cox regression were not used because only one variable (cyclin A) had shown statistical significance (P=.02), whereas the other significant factor (residual tumor) had few cases. Conclusions: Cyclin A IHC should be considered as a marker for the prediction of WT CSS. Prospective studies with a larger sample size are needed.

Keywords: wilms’ tumour, nephroblastoma, urology, survival

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Authors: Abu Salim Mustafa

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Brucellosis is a zoonotic disease endemic in Kuwait. Human brucellosis can be caused by several Brucella species with Brucella melitensis causing the most severe and Brucella abortus the least severe disease. Furthermore, relapses are common after successful chemotherapy of patients. The classical biochemical methods of culture and serology for identification of Brucellae provide information about the species and serotypes only. However, to differentiate between relapse and reinfection/epidemiological investigations, the identification of genotypes using molecular methods is essential. In this study, four molecular methods [16S rRNA gene sequencing, real-time PCR, enterobacterial repetitive intergenic consensus (ERIC)-PCR and multilocus variable-number tandem-repeat analysis (MLVA)-16] were evaluated for the identification and typing of 75 strains of Brucella isolated in Kuwait. The 16S rRNA gene sequencing suggested that all the strains were B. melitensis and real-time PCR confirmed their species identity as B. melitensis. The ERIC-PCR band profiles produced a dendrogram of 75 branches suggesting each strain to be of a unique type. The cluster classification, based on ~ 80% similarity, divided all the ERIC genotypes into two clusters, A and B. Cluster A consisted of 9 ERIC genotypes (A1-A9) corresponding to 9 individual strains. Cluster B comprised of 13 ERIC genotypes (B1-B13) with B5 forming the largest cluster of 51 strains. MLVA-16 identified all isolates as B. melitensis and divided them into 71 MLVA-types. The cluster analysis of MLVA-16-types suggested that most of the strains in Kuwait originated from the East Mediterranean Region, a few from the African group and one new genotype closely matched with the West Mediterranean region. In conclusion, this work demonstrates that B. melitensis, the most pathogenic species of Brucella, is prevalent in Kuwait. Furthermore, MLVA-16 is the best molecular method, which can identify the Brucella species and genotypes as well as determine their origin in the global context. Supported by Kuwait University Research Sector grants MI04/15 and SRUL02/13.

Keywords: Brucella, ERIC-PCR, MLVA-16, RT-PCR, 16S rRNA gene sequencing

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Authors: Maximo Cozzetti

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The aim is to evaluate the capability of the 'Siberian Husky' (FCI-Standard Nº 270) breed of the common dog (Canis lupus familiaris) to detect terminally-ill human patients undergoing palliative care. A total of 49 such patients that fulfill the 'National Scientific and Technical Research Council–Ethical Principles for the Behavior of the Scientific and Technical Investigator' policy, (mainly affected with Stage IV Hodgkin lymphoma or Stage IV Carcinoma, though various other terminal diseases were present) and 49 controls were enrolled. A total of 13 specimens of Siberian Huskies (Canis lupus familiaris FCI – Standard Nº 270) were selected. After a conditioning training regime in which the canines were rewarded when identifying terminally ill patients and excluding the control subjects, a double-blind experiment was conducted in which the canines were presented with a previously unknown patient through an olfactory-proof plexiglass window for 2-minute intervals. The test subjects correctly identified 89.80% of the humans as either ‘ill’ or ‘healthy’. It is important to note that both groups of humans were selected considering and preventing confounding and self-identifying factors such as age, ethnicity, clothing, posture, skin color, alopecia (chemotherapy-induced or otherwise), etc. The olfactory-proofing of the test area rules out the use of the sense of smell to detect distinctive drugs or bodily odors that may be associated with terminal diseases. Thus, the Siberian Husky breed of the common dog shows the visual capability to detect and identify terminally ill patients undergoing palliative care regardless of age, posture, and quantity of hair. Though the capability of the breed of dog to detect terminally-ill patients was observed thoroughly during the course of the experiments, the exact process by which the canines identify the test subjects remains unknown and further research is encouraged.

Keywords: Canis lupus familiaris, Siberian Husky, visual identification of terminall illness, FCI-Standard Nº270

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Authors: Ahlam H. Mahmoud, Samir F. Zohny, Ibrahim H. Boraia, Faten S. Bayoumic, Eman Eissa

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Hepatocellular carcinoma is one of the most common cancers worldwide and is known to be resistant to conventional chemotherapy. Therefore, we aimed to assess the Salsola inermis extract as a novel chemopreventive and/or therapeutic agent against N-nitrosodiethylamine (DNE)/phenobarbital (PB)-induced hepatocarcinogenesis in rats. Adult male Wistar albino rats were divided into five groups: group1 rats were served as normal controls; group 2 rats were injected intraperitoneally with S. inermis extract (100 mg/kg body weight/day) for 20 weeks; group 3 rats were subjected to two-phase hepatocarcinogenic regimen (initiation of hepatocarcinogenesis was performed by a single intraperitoneal injection of DEN at a dose of 200 mg/kg body weight, 2 weeks later, the carcinogenic effect was promoted by supplementation of rats with 0.05% PB for 16 weeks); group 4 rats were injected intraperitoneally with S. inermis extract 2 weeks prior to the injection of DEN, the daily injection of S. inermis extract was then continued for 18 weeks along with two-phase hepatocarcinogenic regimen (chemoprevention group); and group 5 rats were subjected to the two-phase hepatocarcinogenic regimen, and then, the animals were injected intraperitoneally with S. inermis extract for 4 weeks (treatment group). The activities of serum liver enzymes and levels of total bilirubin, conjugated bilirubin, α-fetoprotein, vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in serum were decreased in chemopreventive and treated rats compared with DEN/PB-administered rats. Interestingly, the serum levels of total protein and albumin were normalized in chemopreventive and treated rats. Moreover, the majority of chemopreventive and treated rats showed an almost normal histological pattern of liver. In conclusion, S. inermis extract possessed chemopreventive and therapeutic activities against hepatocarcinogenesis in rats partially through the inhibition of VEGF and sICAM-1.

Keywords: Salsola inermis extract, hepatocarcinogenesis, α–fetoprotein, VEGF, sICAM-1

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Authors: Ralene Sim, Stefan Mueller, N. Gopalakrishna Iyer, Ngian Chye Tan, Khee Chee Soo, R. Shetty Mahalakshmi, Hiang Khoon Tan

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Background: Regional failure in nasopharyngeal carcinoma (NPC) is managed by salvage treatment in the form of neck dissection. Radical neck dissection (RND) is preferred over modified radical neck dissection (MRND) since it is traditionally believed to offer better long-term disease control. However, with the advent of more advanced imaging modalities like high-resolution Magnetic Resonance Imaging, Computed Tomography, and Positron Emission Tomography-CT scans, earlier detection is achieved. Additionally, concurrent chemotherapy also contributes to reduced tumour burden. Hence, there may be a lesser need for an RND and a greater role for MRND. With this retrospective study, the primary aim is to ascertain whether MRND, as opposed to RND, has similar outcomes and hence, whether there would be more grounds to offer a less aggressive procedure to achieve lower patient morbidity. Methods: This is a retrospective study of 66 NPC patients treated at Singapore General Hospital between 1994 to 2016 for histologically proven regional recurrence, of which 41 patients underwent RND and 25 who underwent MRND, based on surgeon preference. The type of ND performed, primary treatment mode, adjuvant treatment, and pattern of recurrence were reviewed. Overall survival (OS) was calculated using Kaplan-Meier estimate and compared. Results: Overall, the disease parameters such as nodal involvement and extranodal extension were comparable between the two groups. Comparing MRND and RND, the median (IQR) OS is 1.76 (0.58 to 3.49) and 2.41 (0.78 to 4.11) respectively. However, the p-value found is 0.5301 and hence not statistically significant. Conclusion: RND is more aggressive and has been associated with greater morbidity. Hence, with similar outcomes, MRND could be an alternative salvage procedure for regional failure in selected NPC patients, allowing similar salvage rates with lesser mortality and morbidity.

Keywords: nasopharyngeal carcinoma, neck dissection, modified neck dissection, radical neck dissection

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Authors: Tanakrit Doltanakarn

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Introduction: These days, cannabis is being accepted in many countries due to the fact that cannabis could be use in medical. The medical cannabis is used to treat and reduce the pain many diseases. For example, neuropathic pain, Parkinson, autism disorders, cancer pain reduce the adverse effect of chemotherapy, diabetes, and migraine. Active ingredients in cannabis that modulate patients' perceptions of their conditions include Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), flavonoids, and terpenes. However, there is an adverse effect of cannabis, cardiovascular effects, psychosis, schizophrenia, mood disorder, and cognitive alternation. These effects are from the THC and CBD ingredients in the cannabis. The metabolize processes of delta-9 THC to 11-OH-delta 9 -THC (inactive form), THC were cause of adverse effects. Interestingly, the distributions of CYP2C9 gene (CYP2C9*2 and CYP2C9*3, poor metabolizer) that might affect incidences of adverse effects in patients who treated with medical cannabis. Objective: The aim of this study we want to investigate the association between genetic polymorphism of CYP2C9 frequency and Thai patients who treated with medical cannabis. Materials and Methods:We recruited sixty-five unrelated Thai patients from the College of Pharmacy, Rangsit University. DNA were extracted using Genomic DNA Mini Kit. Genotyping of CYP2C9*2 (430C>T, rs1799853) and CYP2C9*3 (1075A>C, rs1057910) were genotyped by the TaqMan Real-time PCR assay. Results: Among these 31 medicals cannabis-induced ADRs patients, they were diagnosed with 22 (33.85%) tachycardia and 3 (4.62%) arrhythmia. There were 34 (52.31%) medical cannabis-tolerant controls who were included in this study.40 (61.53%) Thai patients were female, and 25 (38.46%) were male, with median age of 57 (range 27 – 87) years. In this study, we found none of the medical cannabis-induced ADRs carried CYP2C9*2 variant along with medical cannabis-tolerant control group. CYP2C9*3 variant (intermediate metabolizer, IM) was found just only one of thirty-one (3.23%) in the medical cannabis-induced ADRs and two of thirty-fourth (5.88%) in the tolerant controls. Conclusions: Thus, the distribution of CYP2C9 alleles offer a comprehensive view of pharmacogenomics marker in Thai population that could be used as a reference for worldwide to investigate the pharmacogenomics application.

Keywords: medical cannabis, adverse effect, CYP2C9, thai patients

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Authors: Prathama Guha Chaudhuri, Arunima Datta, Ashis Mukhopadhyay

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Background: Visualization (guided imagery) is a set of techniques which induce relaxation and help people create positive mental images in order to reduce stress.It is relatively inexpensive and can even be practised by bed bound people. Studies have shown visualization to be an effective tool to improve cancer patients’ anxiety, depression and quality of life. The common images used with cancer patients in the developed world are those involving the individual’s body and its strengths. Since breast cancer patients in India are more family oriented and often their main concerns are the stigma of having cancer and subsequent isolation of their families, including their children, we figured that positive images involving acceptance and integration within family and society would be more effective for them. Method: Data was collected from 119 breast cancer patients on chemotherapy willing to undergo psychotherapy, with no history of past psychiatric illness. Their baseline stress, anxiety, depression and quality of life were assessed using validated tools. The participants were then randomly divided into three groups: a) those who received visualization therapy with standard imageries involving the body and its strengths (sVT), b) those who received visualization therapy using indigenous family oriented imageries (mVT) and c) a control group who received supportive therapy. There were six sessions spread over two months for each group. The psychological outcome variables were measured post intervention. Appropriate statistical analyses were done. Results:Both forms of visualization therapy were more effective than supportive therapy alone in reducing patients’ depression, anxiety and quality of life.Modified VT proved to be significantly more effective in improving patients’ anxiety and quality of life. Conclusion: Visualization is a valuable therapeutic option for reduction of psychological distress and improving quality of life of breast cancer patients.In order to be more effective, the images used need to be modified according to the sociocultural background and individual needs of the patients.

Keywords: breast cancer, visualization therapy, quality of life, anxiety, depression

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Authors: Tedman Cheuk-Yiu Chau, Xavier Harvey, Hung Nguyen

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Defunctioning ileostomies are frequently used as an adjunct to low anterior resection in the surgical treatment of rectal cancer. Despite reducing the rate of clinically relevant anastomotic leak, the burden of defunctioning ileostomy is significant, with up to two-thirds of patients reporting stoma-related morbidity. International data have demonstrated an increased risk of bowel dysfunction and lower quality of life in patients with delayed closure (greater than six months post-surgery). While timely reversal is safe and cost-effective, the time to the reversal in Australian and New Zealand public hospitals is not described in the published literature. Thus, it is important to assess the current timeliness of ileostomy closure in the Australian regional context and examine the reasons for the delay. A retrospective analysis of ileostomy closure in Launceston General Hospital (LGH) patients treated with low/ultra low anterior resection for rectal cancer between 2012 and 2019 was undertaken. 94 cases of rectal adenocarcinoma undergoing ultralow anterior resection were examined over the years between 2012-2019. Amongst these, 21 cases (22.3%) were not reversed due to disease progress, death prior to reversal, or surgical complication. Demographics, disease status, surgical technique, and hospital inpatient events of these cases were examined. An average waiting time of 213.2 days was noted. Reasons for the delay include non-specified/prolonged hospital waiting time (54%), delayed or complicated chemotherapy course (13%), surgical complication (11%), advanced age, and frailty(5%). Complication of a delayed ileostomy reversal includes post-operation ileus and the development of an incisional hernia. We conclude that a delayed reversal of ileostomy can contribute to a higher incidence of stoma-related co-morbidities and contribute to a longer hospital stay and therefore use of public hospital resources.

Keywords: anterior resection, colorectal surgery, ileostomy reversal, rectal cancer

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Authors: Aamna Tufail, Kajal Kotecha, Iordanis Toursounidis, Ravinder Pabla

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Introduction/Aims: Acute Myeloid Leukaemia (AML) is a part of leukaemic group of hematopoietic disorders with a varying range of presentations, including oro-facial manifestations. Early recognition and management are essential for favourable outcomes. Materials and Methods: We present our experience, clinical presentation, and clinical photographs of a patient with previously undiagnosed AML who presented with oral symptoms to the emergency department of our hospital. An analysis of clinical characteristics, diagnostic investigations, and management modalities was performed. Results/Statistics: A 58-year-old man presented to A&E reporting an 11-day history of right sided facial swelling, acute TMJ symptoms, and oral discomfort. A dentist ruled out acute dental causes one day post onset of symptoms. Initial assessment was anatomically inconsistent and did not reveal a routine oral or maxillofacial etiology. Detailed clinical examination demonstrated fever, generalised pallor, swelling and erythema of right nasolabial region, bilateral masseteric tenderness, intraoral palatal ecchymosis, palatal ulceration, buccal and labial petechiae, cervical lymphadenopathy, and haematoma on dorsum of right hand overlying right 2nd metacarpal joint. Suspecting a systemic medical cause, we requested haematological investigations, which revealed neutropenia, thrombocytopenia, and anaemia. Flow cytometry confirmed CD34 + AML. Oral discomfort was managed symptomatically. The patient was referred to a tertiary care centre for acute haematologic care, where he was treated with IV antibiotics and continuing cycles of chemotherapy. Conclusions/Clinical Relevance: Oro-facial manifestations may be the first clinical sign of AML. Awareness of its features is vital in early diagnosis. In this context, dentists and oral medicine specialists can play an important role in detecting clinical signs of haematological disorders such as AML.

Keywords: acute myeloid leukaemia, oral symptoms, ulceration, diagnosis, management

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