Search results for: Roslan Hashim
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 102

Search results for: Roslan Hashim

12 Strategic Business Solutions for an Ageing SME

Authors: N. G. Teik Hiang, Fathyah Hashim

Abstract:

This is a case of how strategic management techniques can be used to help resolving problems faced by an ageing Small and Medium Enterprise (SME). Strategic way of resolving problems had been proven to be possible in this case despite general thought that strategic management is useful mostly for large corporations. Small and Medium Enterprises (SMEs) can also use strategic management in managing their business and determining their future cause of action and strategies in order to survive in this ever competent world. Strategic orientation is the key to survival and development of small and medium enterprises. In order to adapt to the fierce market competition, ageing SMEs should improve competitiveness and operational efficiency. They must therefore establish a sense of strategic management to improve the strategic management skills, combined with its own unique characteristics, and work out practical strategies to develop core competitiveness of enterprises in the fierce market competition in order to be sustainable. In this case, internal strengths and weaknesses of an SME had been identified. Strategic internal factors and external factors had been classified and further utilized to formulate potential strategies to encounter various problems faced by the SME. These strategies had been further match to take advantages of the opportunities and to overcome the weaknesses and minimize the threats it is facing. Tan, a consultant who was given the opportunity to formulate a plan for the business started with the environmental scanning (internal and external environmental analysis), assessing strengths and weaknesses for the company, strategies generation, analysis and evaluation. He had numerous discussions with the owner of the business and the senior management in order to match the key internal and external factors to formulate alternative strategies for solving the problems that the company facing. Some of the recommendations or solutions are generated from the inspiration of the owner of the business who is a very enterprising and experience businessman.

Keywords: strategic orientation, strategic management, SME, core competitiveness, sustainable

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11 Measurement and Monitoring of Graduate Attributes via iCGPA Implementation and ACADEMIA Programming: UNIMAS Case Study

Authors: Shanti Faridah Salleh, Azzahrah Anuar, Hamimah Ujir, Rohana Sapawi, Wan Hashim Wan Ibrahim, Noraziah Abdul Wahab, Majina Sulaiman, Raudhah Ahmadi, Al-Khalid Othman, Johari Abdullah

Abstract:

Integrated Cumulative Grade Point Average or iCGPA is an evaluation and reporting system that represents a comprehensive development of students’ achievement in their academic programs. Universiti Malaysia Sarawak, UNIMAS has started its implementation of iCGPA in 2016. iCGPA is driven by the Outcome-Based Education (OBE) system that has been long integrated into the higher education in Malaysia. iCGPA is not only a tool to enhance the OBE concept through constructive alignment but it is also an integrated mechanism to assist various stakeholders in making decisions or planning for program improvement. The outcome of this integrated system is the reporting of students’ academic performance in terms of cognitive (knowledge), psychomotor (skills), and affective (attitude) of which the students acquire throughout the duration of their study. The iCGPA reporting illustrates the attainment of student’s attribute in the eight domains of learning outcomes listed in the Malaysian Qualifications Framework (MQF). This paper discusses on the implementation of iCGPA in UNIMAS on the policy and strategy to direct the whole university to implement the iCGPA. The steps and challenges in integrating the exsting Outcome-Based Education and utilising iCGPA as a tool to quantify the students’ achievement are also highlighted in this paper. Finally, the ACADEMIA system, which is a dedicated centralised program ensure the implementation of iCGPA is a success has been developed. This paper discusses the structure and the analysis of ACADEMIA program and concludes the analysis made on the improvement made on the implementation of constructive alignment in all 40 programs involves in iCGPA implementation.

Keywords: constructive alignment, holistic graduates, mapping of assessment, programme outcome

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10 Satureja bachtiarica Bunge Induce Apoptosis via Mitochondrial Intrinsic Pathway and G1 Cell Cycle Arrest

Authors: Hamed Karimian, Noraziah Nordin, Mohamad Ibrahim Noordin, Syam Mohan, Mahboubeh Razavi, Najihah Mohd Hashim, Happipah Mohd Ali

Abstract:

Satureja bachtiarica Bunge is a perennial medicinal plant belonging to the Lamiaceae family and endemic species in Iran. Satureja bachtiarica Bunge with the local name of Marzeh koohi is edible vegetable use as flavoring agent, anti-bacterial and to relieve cough and indigestion. In this study, the anti-cancer effect of Satureja bachtiarica Bunge on the MDA-MB-231 cell line as an Breast cancer cell model has been analyzed for the first time. Satureja bachtiarica Bunge was extracted using different solvents in the order of increasing polarity. Cytotoxicity activity of hexane extract of Satureja bachtiarica Bunge (SBHE) was observed using MTT assay. Acridine orange/Propidium iodide staining was used to detect early apoptosis; Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS), with Annexin-Vserving as a marker for apoptotic cells. Caspase 3/7, 8 and-9 assays showed significantly activation of caspase-9 where lead intrinsic mitochondrial pathway. Bcl-2/Bax expressions and cell cycle arrest were also investigated. SBHE had exhibited significantly higher cytotoxicity against MDA-MB-231 Cell line compare to other cell lines. A significant increase in chromatin condensation in the cell nucleus was observed by fluorescence analysis. Treatment of MDA-MB-231 cells with SBHE encouraged apoptosis, by down-regulating Bcl-2 and up-regulating Bax, which lead the activation of caspase 9. Moreover, SBHE treatment significantly arrested MDA-MB-231 cells in the G1 phase. Together, the results presented in this study demonstrated that SBHE inhibited the proliferation of MDA-MB-231 cells, leading cell cycle arrest and programmed cell death, which was confirmed to be through the mitochondrial pathway.

Keywords: Satureja bachtiarica Bunge, MDA-MB-231, apoptosis, annexin-V, cell cycle

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9 Rectus Sheath Block to Extend the Effectiveness of Post Operative Epidural Analgesia

Authors: Sugam Kale, Arif Uzair Bin Mohammed Roslan, Cindy Lee, Syed Beevee Mohammed Ismail

Abstract:

Preemptive analgesia is an established concept in the modern practice of anaesthesia. To be most effective, it is best instituted earlier than the surgical stimulus and should last beyond the offset of surgically induced pain till healing is complete. Whereas the start of afferent pain blockade with regional anaesthesia is common, its effect often falls short to cover the entire period of pain impulses making their way to CNS in the post-operative period. We tried to use a combination of two regional anaesthetic techniques used sequentially to overcome this handicap. Madam S., a 56 year old lady, was scheduled for elective surgery for pancreatic cancer. She underwent laparotomy and distal pancreatectomy, splenectomy, bilateral salpingo oophorectomy, and sigmoid colectomy. Surgery was expected to be extensive, and it was presumed that the standard pain relief with PCA with opiates and oral analgesics would not be adequate. After counselling the patient pre-operative about the technique of regional anaesthesia techniques, including epidural catheterization and rectus sheath catheter placement, their benefits, and potential complications, informed consent was obtained. Epidural catheter was placed awake, and general anaesthesia was then induced. Epidural infusion of local anaesthetics was started prior to surgical incision and was continued till 60 hours into the postoperative period. Before skin closure, the surgeons inserted commercially available rectus sheath catheters bilaterally along the midline incision used for laparotomy. After 46 hours post-op, local anaesthetic infusion via these was started as bridging while the epidural infusion rate was tapered off. The epidural catheter was removed at 75 hours. Elastomeric pumps were used to provide local anaesthetic infusion with the ability to vary infusion rates. Acute pain service followed up the patient’s vital signs and effectiveness of pain relief twice daily or more frequently as required. Rectus sheath catheters were removed 137 hours post-op. The patient had good post-op analgesia with the minimal additional analgesic requirement. For the most part, the visual analog score (VAS) for pain remained at 1-3 on a scale of 1 to 10. Haemodynamics remained stable, and surgical recovery was as expected. Minimal opiate requirement after an extensive laparotomy also translates to the early return of intestinal motility. Our experience was encouraging, and we are hoping to extend this combination of two regional anaesthetic techniques to patients undergoing similar surgeries. Epidural analgesia is denser and offers excellent pain relief for both visceral and somatic pain in the first few days after surgery. As the pain intensity grows weaker, rectus sheath block and oral analgesics provide almost the same degree of pain relief after the epidural catheter is removed. We discovered that the background infusion of local anaesthetic down the rectus sheath catherter largely reduced the requirement for other classes of analgesics. We aim to study this further with a larger patient cohort and hope that it may become an established clinical practice that benefits patients everywhere.

Keywords: rectus sheath, epidural infusion, post operative analgesia, elastomeric

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8 Pattern Recognition Approach Based on Metabolite Profiling Using In vitro Cancer Cell Line

Authors: Amanina Iymia Jeffree, Reena Thriumani, Mohammad Iqbal Omar, Ammar Zakaria, Yumi Zuhanis Has-Yun Hashim, Ali Yeon Md Shakaff

Abstract:

Metabolite profiling is a strategy to be approached in the pattern recognition method focused on three types of cancer cell line that driving the most to death specifically lung, breast, and colon cancer. The purpose of this study was to discriminate the VOCs pattern among cancerous and control group based on metabolite profiling. The sampling was executed utilizing the cell culture technique. All culture flasks were incubated till 72 hours and data collection started after 24 hours. Every running sample took 24 minutes to be completed accordingly. The comparative metabolite patterns were identified by the implementation of headspace-solid phase micro-extraction (HS-SPME) sampling coupled with gas chromatography-mass spectrometry (GCMS). The optimizations of the main experimental variables such as oven temperature and time were evaluated by response surface methodology (RSM) to get the optimal condition. Volatiles were acknowledged through the National Institute of Standards and Technology (NIST) mass spectral database and retention time libraries. To improve the reliability of significance, it is of crucial importance to eliminate background noise which data from 3rd minutes to 17th minutes were selected for statistical analysis. Targeted metabolites, of which were annotated as known compounds with the peak area greater than 0.5 percent were highlighted and subsequently treated statistically. Volatiles produced contain hundreds to thousands of compounds; therefore, it will be optimized by chemometric analysis, such as principal component analysis (PCA) as a preliminary analysis before subjected to a pattern classifier for identification of VOC samples. The volatile organic compound profiling has shown to be significantly distinguished among cancerous and control group based on metabolite profiling.

Keywords: in vitro cancer cell line, metabolite profiling, pattern recognition, volatile organic compounds

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7 Spectral Mapping of Hydrothermal Alteration Minerals for Geothermal Exploration Using Advanced Spaceborne Thermal Emission and Reflection Radiometer Short Wave Infrared Data

Authors: Aliyu J. Abubakar, Mazlan Hashim, Amin B. Pour

Abstract:

Exploiting geothermal resources for either power, home heating, Spa, greenhouses, industrial or tourism requires an initial identification of suitable areas. This can be done cost-effectively using remote sensing satellite imagery which has synoptic capabilities of covering large areas in real time and by identifying possible areas of hydrothermal alteration and minerals related to Geothermal systems. Earth features and minerals are known to have unique diagnostic spectral reflectance characteristics that can be used to discriminate them. The focus of this paper is to investigate the applicability of mapping hydrothermal alteration in relation to geothermal systems (thermal springs) at Yankari Park Northeastern Nigeria, using Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) satellite data for resource exploration. The ASTER Short Wave Infrared (SWIR) bands are used to highlight and discriminate alteration areas by employing sophisticated digital image processing techniques including image transformations and spectral mapping methods. Field verifications are conducted at the Yankari Park using hand held Global Positioning System (GPS) monterra to identify locations of hydrothermal alteration and rock samples obtained at the vicinity and surrounding areas of the ‘Mawulgo’ and ‘Wikki’ thermal springs. X-Ray Diffraction (XRD) results of rock samples obtained from the field validated hydrothermal alteration by the presence of indicator minerals including; Dickite, Kaolinite, Hematite and Quart. The study indicated the applicability of mapping geothermal anomalies for resource exploration in unmapped sparsely vegetated savanna environment characterized by subtle surface manifestations such as thermal springs. The results could have implication for geothermal resource exploration especially at the prefeasibility stages by narrowing targets for comprehensive surveys and in unexplored savanna regions where expensive airborne surveys are unaffordable.

Keywords: geothermal exploration, image enhancement, minerals, spectral mapping

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6 Is Maternity Discrimination Pushing Women out of Work? A Case Study of Maternity Experiences of Working Women in Malaysia

Authors: Nor Hafizah Selamat, Intan Hashima Mohd Hashim, Noraida Endut, Shariffah Suraya Syed Jamaludin, Sharifah Zahhura Syed Abdullah, Suziana Mat Yasin, Nurul Jannah Ambak

Abstract:

In Malaysia, report on discrimination against pregnant women at work does exist, and this issue should be taken seriously as large proportion of women in the workforce in Malaysia are of reproductive age. It has been well established that women tend to leave the workforce because of their responsibility in raising the family, to care for family members and, also due to lack of work-life balance. In this case, women find themselves disadvantaged in career and job advancements due to gender roles and expectations connected with maternity. This maternity discrimination have pushed women out of work although The Convention on the Elimination of All Forms of Discrimination Against Women (CEDAW), to which Malaysia is a party, considers discrimination on the ground of maternity is a form of gender discrimination because it hinders women of their effective right to work and requires that special protection be provided for women during maternity to ensure their ability to enjoy the right to work (Article 11(2). What factors prevent women from returning to work and at the same time performing their gender roles expectations? Using semi-structured in-depth interviews this paper explores the experiences of maternity discrimination and their perspectives towards their work employment. 15 women employees who were pregnant or had given birth during her employment period in public and private organizations in Malaysia were participated in this study. While data were analyzed using narrative analysis, respondents were asked on issues related to managing pregnancy, maternity leave and returning to work. The findings revealed that several respondents from private companies stated that they were either dismissed or forced to take unpaid leave due to the company policies. In some cases, respondents also shared how they were treated poorly that they felt that they had to leave their jobs. However, in public organization, the maternity policy implemented showed the support that the employees received from their employer. Study shows that supportive family and employers will encourage employees to return to work. Reasonable adjustments in terms of maternity policies at workplace such as allowing sufficient time in postnatal appointments, offering clear explanation on maternity issues at workplace are something that employees expected from their employers.

Keywords: maternity discrimination, women and work, gender, maternity protection, Malaysia

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5 The Yield of Neuroimaging in Patients Presenting to the Emergency Department with Isolated Neuro-Ophthalmological Conditions

Authors: Dalia El Hadi, Alaa Bou Ghannam, Hala Mostafa, Hana Mansour, Ibrahim Hashim, Soubhi Tahhan, Tharwat El Zahran

Abstract:

Introduction: Neuro-ophthalmological emergencies require prompt assessment and management to avoid vision or life-threatening sequelae. Some would require neuroimaging. Most commonly used are the CT and MRI of the Brain. They can be over-used when not indicated. Their yield remains dependent on multiple factors relating to the clinical scenario. Methods: A retrospective cross-sectional study was conducted by reviewing the electronic medical records of patients presenting to the Emergency Department (ED) with isolated neuro-ophthalmologic complaints. For each patient, data were collected on the clinical presentation, whether neuroimaging was performed (and which type), and the result of neuroimaging. Analysis of the performed neuroimaging was made, and its yield was determined. Results: A total of 211 patients were reviewed. The complaints or symptoms at presentation were: blurry vision, change in the visual field, transient vision loss, floaters, double vision, eye pain, eyelid droop, headache, dizziness and others such as nausea or vomiting. In the ED, a total of 126 neuroimaging procedures were performed. Ninety-four imagings (74.6%) were normal, while 32 (25.4%) had relevant abnormal findings. Only 2 symptoms were significant for abnormal imaging: blurry vision (p-value= 0.038) and visual field change (p-value= 0.014). While 4 physical exam findings had significant abnormal imaging: visual field defect (p-value= 0.016), abnormal pupil reactivity (p-value= 0.028), afferent pupillary defect (p-value= 0.018), and abnormal optic disc exam (p-value= 0.009). Conclusion: Risk indicators for abnormal neuroimaging in the setting of neuro-ophthalmological emergencies are blurred vision or changes in the visual field on history taking. While visual field irregularities, abnormal pupil reactivity with or without afferent pupillary defect, or abnormal optic discs, are risk factors related to physical testing. These findings, when present, should sway the ED physician towards neuroimaging but still individualizing each case is of utmost importance to prevent time-consuming, resource-draining, and sometimes unnecessary workup. In the end, it suggests a well-structured patient-centered algorithm to be followed by ED physicians.

Keywords: emergency department, neuro-ophthalmology, neuroimaging, risk indicators

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4 High-Performance Thin-layer Chromatography (HPTLC) Analysis of Multi-Ingredient Traditional Chinese Medicine Supplement

Authors: Martin Cai, Khadijah B. Hashim, Leng Leo, Edmund F. Tian

Abstract:

Analysis of traditional Chinese medicinal (TCM) supplements has always been a laborious task, particularly in the case of multi‐ingredient formulations. Traditionally, herbal extracts are analysed using one or few markers compounds. In the recent years, however, pharmaceutical companies are introducing health supplements of TCM active ingredients to cater to the needs of consumers in the fast-paced society in this age. As such, new problems arise in the aspects of composition identification as well as quality analysis. In most cases of products or supplements formulated with multiple TCM herbs, the chemical composition, and nature of each raw material differs greatly from the others in the formulation. This results in a requirement for individual analytical processes in order to identify the marker compounds in the various botanicals. Thin-layer Chromatography (TLC) is a simple, cost effective, yet well-regarded method for the analysis of natural products, both as a Pharmacopeia-approved method for identification and authentication of herbs, and a great analytical tool for the discovery of chemical compositions in herbal extracts. Recent technical advances introduced High-Performance TLC (HPTLC) where, with the help of automated equipment and improvements on the chromatographic materials, both the quality and reproducibility are greatly improved, allowing for highly standardised analysis with greater details. Here we report an industrial consultancy project with ONI Global Pte Ltd for the analysis of LAC Liver Protector, a TCM formulation aimed at improving liver health. The aim of this study was to identify 4 key components of the supplement using HPTLC, following protocols derived from Chinese Pharmacopeia standards. By comparing the TLC profiles of the supplement to the extracts of the herbs reported in the label, this project proposes a simple and cost-effective analysis of the presence of the 4 marker compounds in the multi‐ingredient formulation by using 4 different HPTLC methods. With the increasing trend of small and medium-sized enterprises (SMEs) bringing natural products and health supplements into the market, it is crucial that the qualities of both raw materials and end products be well-assured for the protection of consumers. With the technology of HPTLC, science can be incorporated to help SMEs with their quality control, thereby ensuring product quality.

Keywords: traditional Chinese medicine supplement, high performance thin layer chromatography, active ingredients, product quality

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3 The Environmental Impact Assessment of Land Use Planning (Case Study: Tannery Industry in Al-Garma District)

Authors: Husam Abdulmuttaleb Hashim

Abstract:

The environmental pollution problems represent a great challenge to the world, threatening to destroy all the evolution that mankind has reached, the organizations and associations that cares about environment are trying to warn the world from the forthcoming danger resulted from excessive use of nature resources and consuming it without looking to the damage happened as a result of unfair use of it. Most of the urban centers suffers from the environmental pollution problems and health, economic, and social dangers resulted from this pollution, and while the land use planning is responsible for distributing different uses in urban centers and controlling the interactions between these uses to reach a homogeneous and perfect state for the different activities in cities, the occurrence of environmental problems in the shade of existing land use planning operation refers to the disorder or insufficiency in this operation which leads to presence of such problems, and this disorder lays in lack of sufficient importance to the environmental considerations during the land use planning operations and setting up the master plan, so the research start to study this problem and finding solutions for it, the research assumes that using accurate and scientific methods in early stages of land use planning operation will prevent occurring of environmental pollution problems in the future, the research aims to study and show the importance of the environmental impact assessment method (EIA) as an important planning tool to investigate and predict the pollution ranges of the land use that has a polluting pattern in land use planning operation. This research encompasses the concept of environmental assessment and its kinds and clarifies environmental impact assessment and its contents, the research also dealt with urban planning concept and land use planning, it also dealt with the current situation of the case study (Al-Garma district) and the land use planning in it and explain the most polluting use on the environment which is the industrial land use represented in the tannery industries and then there was a stating of current situation of this land use and explaining its contents and environmental impacts resulted from it, and then we analyzed the tests applied by the researcher for water and soil, and perform environmental evaluation through applying environmental impact assessment matrix using the direct method to reveal the pollution ranges on the ambient environment of industrial land use, and we also applied the environmental and site limits and standards by using (GIS) and (AUTOCAD) to select the site of the best alternative of the industrial region in Al-Garma district after the research approved the unsuitability of its current site location for the environmental and site limitations, the research conducted some conclusions and recommendations regard clarifying the concluded facts and to set the proper solutions.

Keywords: EIA, pollution, tannery industry, land use planning

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2 A Lightweight Interlock Block from Foamed Concrete with Construction and Agriculture Waste in Malaysia

Authors: Nor Azian Binti Aziz, Muhammad Afiq Bin Tambichik, Zamri Bin Hashim

Abstract:

The rapid development of the construction industry has contributed to increased construction waste, with concrete waste being among the most abundant. This waste is generated from ready-mix batching plants after the concrete cube testing process is completed and disposed of in landfills, leading to increased solid waste management costs. This study aims to evaluate the engineering characteristics of foamed concrete with waste mixtures construction and agricultural waste to determine the usability of recycled materials in the construction of non-load-bearing walls. This study involves the collection of construction wastes, such as recycled aggregates (RCA) obtained from the remains of finished concrete cubes, which are then tested in the laboratory. Additionally, agricultural waste, such as rice husk ash, is mixed into foamed concrete interlock blocks to enhance their strength. The optimal density of foamed concrete for this study was determined by mixing mortar and foam-backed agents to achieve the minimum targeted compressive strength required for non-load-bearing walls. The tests conducted in this study involved two phases. In Phase 1, elemental analysis using an X-ray fluorescence spectrometer (XRF) was conducted on the materials used in the production of interlock blocks such as sand, recycled aggregate/recycled concrete aggregate (RCA), and husk ash paddy/rice husk ash (RHA), Phase 2 involved physical and thermal tests, such as compressive strength test, heat conductivity test, and fire resistance test, on foamed concrete mixtures. The results showed that foamed concrete can produce lightweight interlock blocks. X-ray fluorescence spectrometry plays a crucial role in the characterization, quality control, and optimization of foamed concrete mixes containing construction and agriculture waste. The unique composition mixer of foamed concrete and the resulting chemical and physical properties, as well as the nature of replacement (either as cement or fine aggregate replacement), the waste contributes differently to the performance of foamed concrete. Interlocking blocks made from foamed concrete can be advantageous due to their reduced weight, which makes them easier to handle and transport compared to traditional concrete blocks. Additionally, foamed concrete typically offers good thermal and acoustic insulation properties, making it suitable for a variety of building projects. Using foamed concrete to produce lightweight interlock blocks could contribute to more efficient and sustainable construction practices. Additionally, RCA derived from concrete cube waste can serve as a substitute for sand in producing lightweight interlock blocks.

Keywords: construction waste, recycled aggregates (RCA), sustainable concrete, structure material

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1 Exploiting the Tumour Microenvironment in Order to Optimise Sonodynamic Therapy for Cancer

Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

Abstract:

Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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