Introduction: Even though exclusive breastfeeding prevalence has increased from 19.3% in 2006 to 47.1% in 2016, this practice was slightly higher in urban areas (48.3%) compared to rural area (45.1%) in Malaysia. National Plan of Action for Nutrition of Malaysia III has set an indicator to achieve at least 70% exclusive breastfeeding by 2025. Therefore this study is to identify predictors that influenced exclusive breastfeeding practice in rural areas. Methods: This cross-sectional study was conducted in six rural health clinics in Hulu Langat District, Selangor among moth- ers with youngest child aged 6-48 months old. Respondents were selected through systematic random sampling. Validated self-administered questionnaire was used to assess sociodemographic factors, maternal factors, external factors and child’s factors. Mother’s height and weight was measured and body mass index was calculated. Data were analyzed using SPSS version 23. Multivariate logistic regression was used to determine the predictors for ex- clusive breastfeeding practice. Results: Response rate was 96% with a total of 311 mothers participated in this study. More than half of the mothers exclusively breastfed (52.4%). The predictors for exclusive breastfeeding were Malay ethnicity (AOR=3.951, 95% CI: 1.374-11.358), having tertiary education (AOR=2.401, 95% CI: 1.100-5.241) and positive attitude toward breastfeeding (AOR=7.755, 95% CI: 1.382-43.502). Conclusion: Prevalence of exclusive breastfeeding was higher in this study than the national level. Programme planners should pay special attention to Chinese and Indian ethnicities, mothers with lower level of education and negative attitude in order to improve breastfeeding practice among rural mothers.
Introduction: Sustained optimal adherence to antiretroviral therapy (ART) is required for long-term suppression of vi- ral replication. However, adherence level in Jos, Nigeria has been reported to be below optimal adherence, thus this study investigates the predictors of adherence to antiretroviral therapy among Human Immunodeficiency Virus (HIV) patients there. Methods: A validated and pretested questionnaire was used in this cross-sectional study to collect data on sociodemographic characteristics, duration of being on ART, alcohol consumption, presence of symptoms, drug type and disclosure status from 224 randomly selected adult HIV patients. Chi-square and binary logistics re- gression were used for data analysis. Level of significance was set at 0.05. Results: Only 14.3% of the respondents had optimal adherence. Adherence to ART is significantly associated with gender (p = 0.043), duration of ART use (p = 0.041), alcohol (p = 0.029), drug type (p = 0.001), and disclosure status (p = 0.004). Binary logistics regression reveals that females are 2.4 times more likely to have optimal adherence than males, patients on ART for over 10 years are 2.5 times more likely to have optimal adherence than those less than 10 years, and patients with disclosed HIV status are 3.3 times more likely to have optimal adherence than those who had not. Conclusion: Generally, the patients had suboptimal adherence. Being female, having longer duration on ART and disclosure status are predictors for optimal adherence. Intervention with emphasis on males and new patients on ART is recommended to educate on optimal adherence and motivate patients to disclose their status.
Introduction: Malaysia is known for its shy and prudent community that indirectly causing the stigma and taboos related to later life sexuality. This study aimed to explore the sexual desire and satisfaction in later life among the Malay ethnic elderly in Malaysia who were living in the urban area, where discussions about sexual issues are per- ceived less sensitive and stigmatized. Methods: A total of 234 eligible elderly were approached but only 160 older people completed the questionnaire, sampled using multistage cluster sampling method. Face-to-face interviews were conducted using questionnaires consisted of sociodemographic characteristics, cognitive function, perceived health status, presence of chronic illnesses, smoking history, disability, perceived sexual problems, sexual desire and satisfaction. Multiple logistic regression was conducted to determine the associated factors for sexual desire and satisfaction, respectively. All tests significant level was set at 0.05. Results: Majority of the respondents were having sexual desire (53.8%) and not satisfied with their sexual life (51.3%), with elderly women (55.7%) experienced more sexual problems compared to men. The results showed male, being married, good perceived health and absence of arthritis were the significant contributing factors of better sexual desire. Having good health perception, being mar- ried and absence of sexual problems were significantly predicting better sexual satisfaction. Conclusion: The study emphasized the multifactorial aspects contributed towards the sexual dissatisfaction among the respondents despite having desire for sexual activity. Focus should be given to elderly women who tend to have multiple chronic diseases and more likely a widow due to their longer life expectancy.
Introduction: The increasing prevalence of depression has been a major public health concern. Being a marginalized population put the inmates at risk of depression. The main objective of this study was to identify the determinants of depression among the inmates according to the biopsychosocial model. Methods: A cross sectional study involv- ing 460 male inmates was conducted at a medium security prison in Seremban. Only Malaysian adult prisoners who have been convicted and had spent a minimum of three months in the prison were eligible for the study. They were selected using the probability proportional to size using stratified random sampling. Data was collected using validated and pre-tested questionnaire by face-to-face interviews, with depression was measured using the Center for Epidemiologic Studies Depression (CES-D) Scale. The data were analyzed using IBM SPSS version 22 with a p-value less than 0.05 was considered statistically significant. Results: The results showed prevalence of depression were 40.70% (95% CI: 36.21-45.19) with its development being predicted by presence of communicable disease (AOR=2.145, 95% CI: 1.123-4.095), history of childhood abuse (AOR=1.762, 95% CI: 1.045-2.972), sentences of more than 5 years (AOR=3.801, 95% CI: 1.529-9.450), being non-Muslims (AOR=2.261, 95% CI: 1.461-3.497) and perceived stress (AOR=4.007, 95% CI= 2.610-6.151). Conclusions: This study revealed an alarmingly high preva- lence of depression among the male inmates, with stress being the strongest risk factor. Reintegration of the prisoners into the community should be considered as part of the rehabilitation program to ensure continuation of psychiatric care and reduce relapsing.
Introduction: Family planning allows couples to have their desired number of children and optimum birth spacing. While the contraceptive prevalence rate (CPR) in Malaysia was reported as 52.2% in 2014, little is known regard- ing the practice of family planning among marginalised groups such as the Orang Asli women. This study aims to determine family planning practice among married Orang Asli women in Sepang district and its associated factors. Methods: A cross sectional study using a pretested questionnaire was conducted in five Orang Asli settlements in Sepang using cluster sampling. Chi-square test and simple logistic regression were used in bivariate analysis, where- as binary logistic regression was used to determine the predictors of family planning practice. Results: 212 (58.4%) participants were current users of family planning, with 68.3% of the users reported using oral contraceptive pills. In the logistic regression models, family planning practice was significantly more common among women who had children (AOR= 43.659, 95% CI: 5.788, 329.323), being housewives (AOR=1.973, 95% CI: 1.205, 3.230) and had higher attitude score (AOR=1.113, 95% CI: 1.006, 1.232). Conclusion: The CPR of current study was about the same as the national CPR in 2014. The predictors of family planning practice among Orang Asli women were having chil- dren, being a housewife and having a better attitude towards family planning. Future intervention to increase the CPR should focus on improving women’s attitude regarding family planning.
Introduction: Mental problems have become increasingly important public health issue globally. This study aimed to determine the prevalence and factors associated with depression, anxiety, and stress among medical students in a public university in Malaysia. Methods: A total of 447 medical students were sampled by stratified proportion- ate to size sampling according to year of study. Validated self-administered questionnaire was used consisted of 5 sections namely, socio-demographic factors, social support received from family members and friends, presence of co-morbidity, previous history of resolved mental problem and Depression Anxiety Stress Scale DASS- 21. Data was analysed by using the statistical computer software ‘Statistical Package for Social Science (SPSS)’ version 22 involving three levels of analysis (descriptive, chi square and multiple logistic regression). Results: Only 31.1% of the respon- dents were found to be depressed with mainly within the moderately depressed category, 53.9% had anxiety and 26% were having stress. Perceived social support received from family members was a significant predicting factor for depression, anxiety and stress. Conclusion: High proportion of depression, anxiety and level of stress among medical students were found. The stressful medical program is putting medical students at risk of mental problems. Parents and family members should be encouraged to be more involved in any related programs to promote better mental health and well-being of medical students.
Introduction: Many studies have investigated the knowledge and attitude towards breastfeeding among fathers and mothers, however studies looking at working adults’ knowledge and attitude towards breastfeeding is limited. Work- ing adults with good knowledge and favourable attitude toward the practice of breastfeeding may increase the breast- feeding initiative among working mothers. Therefore, the objective of this study was to investigate the knowledge and attitude toward breastfeeding among staff from the Faculty of Medicine and Health Sciences of a public univer- sity and its associated factors. Methods: A cross sectional study was conducted among faculty staff members. The respondents were selected by simple random sampling and a self-administered questionnaire was used to investigate the knowledge and attitude towards breastfeeding among them. Multiple linear regression was used to determine the factors associated with knowledge and attitude respectively. Results: A total of 117 respondents were recruited to take part in this study. Of these, 83(70.9%) had good knowledge while 61(52.6%) respondents had favourable attitude toward breastfeeding. There was significant positive fair correlation between knowledge and attitude score (r=0.396,p
Introduction: To date, lung cancer has become increasingly prevalent and remains the leading cause of cancer-related death in both sexes, globally. Despite the advances of cancer treatment, systemic chemotherapy remains as the major treatment option for lung cancer. Nevertheless, the trend of chemotherapy resistance has restricted the efficacy of the chemotherapy treatment, thus leading the urge to develop an alternative chemotherapeutic agent which could give a promising treatment effect. Short peptides have acquired increasing interest as promising therapeutics due to its anticancer potential, rapid kinetics, high potency and low biocompatibility issue. In search of novel anti-cancer leads, the main objective of this study is to evaluate the in vitro antiproliferative properties of hybridized peptide analogues against human lung adenocarcinoma (A549) cell line. Methods: ND and DN analogues were designed based on two parent peptides, NDC1 and NDC2, through fragments hybridization approach. Modification of amino acid residues at specific positions of NDC1 and NDC2 was done at the C-terminal. Then, MTT assay was performed to examine the antiproliferative activities of NDC1, NDC2, NDs and DNs against A549 cells at concentrations ranging from 2-256μg/mL for 24 hours. Results: Findings obtained showed that the parental peptides, NDC1 and NDC2, exhibited IC50 values of 47.5±4.950μg/mL and 239±9.899μg/mL, respectively. All NDs showed excellent antiproliferative activities with IC50 values ranging from 22-71μg/mL. Nevertheless, all DNs did not display antiproliferative activity when tested up to 256μg/mL. We speculated that increased valine and isoleucine with decreased aspartic acid composition in NDs might be associated with their intermediate cytotoxicity strength, comparing with the parent peptides. However, the location of other amino acids in the peptide sequence should still be further investigated as it contributes to the peptide structure, hence leading to its selectivity and potency. Conclusion: As a conclusion, NDs could be further explored to develop a potent anti-cancer therapeutic drug.
Introduction: Cancer has become a major economic and societal burden. The National Cancer Registry of Malaysia (NCR) estimates that one in four Malaysian (1:4) will develop cancer by the age of 75. This project aims to develop a prototype named “Laser ablation needle” for tissue cauterization and percutaneous hyperthermia cancer therapy. Our ultimate goal is to develop a highly flexible, operator-friendly and cost-effective laser ablation needle for tissue cauterization and hyperthermia cancer therapy, hence to improve the overall cancer survival rate and quality of life among the cancer patient population. Methods: The laser ablation needle is a closed loop opto-electronic control system, consists of a 2 mm Fiber Bragg Grating (FBG) – optical fiber temperature sensor, a laser driven hot needle and a micro-controller. Based on real-time temperature input from the FBG sensor, the micro-controller can perform a dynamic PID control on laser intensity for a safe hyperthermia treatment. In the fabrication, a medical grade optical fiber with a diameter of 800 μm was used for laser delivery. The optical fiber was embedded inside a biocompatible resin-made needle and connected to a 450 nm high power blue laser diode. The FBG temperature sensor was incorporated in the needle for real-time temperature monitoring and control. Focal hyperthermia produced by the laser-driven hot needle was conducted on ex-vivo bovine liver. Results: The rise in temperature was recorded by increasing laser power. The temperature profile was obtained at each depth. Irreversible thermal denaturation during irradiation was captured. Conclusion: These preliminary results suggest that this technique can be applied safely and effectively for cancer treatment. The developed prototype comprised of the diode laser showed that it can deliver its energy via simple optical fiber. This laser is cheaper and much smaller than the conventional high power lasers used in other studies.
Introduction: Lipoprotein L21 (LipL21) has been used as a molecular marker for leptospirosis as it is highly expressed in pathogenic Leptospira species during infection. However, it lacks specificity due to the newly emerging pathogenic serovars. Therefore, interrogation of LipL21 in all serovars needed to understand the pathogenesis of leptospirosis to enable early diagnosis. This study was carried out to determine the suitability of LipL21 as a molecular marker for leptospirosis by identifying the conserved sequences of LipL21 mRNA and amino acids in different Leptospira strains. Methods: Location of LipL21 conserved regions in 15 pathogenic and 2 non-pathogenic strains of five Leptospira species, were identified using bioinformatics database and tools such as National Center of Biotechnology, Rapid Annotation Subsystem Technology blast search, Muscle program and Jalview software. Results: Multiple sequence alignment analysis revealed that two conserved regions were observed in 10 pathogenic Leptospira strains from nucleotide position 29 to 53 and 100 to 137, however conserved amino acid sequences (111-149 and 155-192) were found in all the pathogenic strains. The distinction between gene and amino acid results is due to the degenerate genetic code feature. Conclusion: In conclusion, this study suggests that LipL21 protein has a potential to be used as a diagnostic marker for detection of Leptospira pathogens compared to LipL21 mRNA.
Introduction: We aimed to investigate the moderating role of internal health locus of control, breast cancer worry and age in the relationship between fear of negative appearance evaluation and attitude towards mammography in women with no prior mammography screening experience. Methods: A descriptive and cross-sectional, questionnaire- based survey was conducted. Participants included 823 Iranian women aged 30 years and above. We used covariance- based structural equation modeling to test the research hypotheses. Results: The findings provided evidence for the negative association between fear of negative appearance evaluation and women’s attitudes towards mammography. Internal health locus of control, breast cancer worry, and age weakened the detrimental effect of fear of negative appearance evaluation on mammography screening. We found that fear of negative appearance evaluation could more likely act as a barrier towards mammography screening in women who were less likely to have a sense of control over their own health, who were less worried about developing breast cancer, and who were younger. Conclusion: Implications of the study are discussed with recommendations for future research.
Introduction: Gynura crepioides (G. crepioides) belongs to the Asteraceae family and native to Southeast Asia, especially Indonesia. Gynura genuses are well known for their antioxidant properties. Hence, the current study aimed to study the effect of temperature on polyphenololic content and antioxidant properties on G. crepioides leaves extract. Methods: The extraction of G. crepioides leaves was carried out by Ultrasound-assisted extraction (UAE) method for 60 minutes by using ethanol (70 %) at three different temperatures 25°C and 50°C and 75°C. The total polyphenolic content (TPC) was investigated by using Folin-Ciocalteu assay, whereas the antioxidant potential (AOP) was determined by using phosphomolybdenum assay, and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Results: The results from the study showed that TPC of G. crepioides extracted at 25°C was significantly (p < 0.05) lower than 50°C and 75°C with 8.45 ± 0.31 mg GAE/g, 35.83 ± 1.22 mg GAE/g, 35.90 ± 0.78 mg GAE/g respectively. However, the results from AOP has demonstrated lower value of 70.62 ± 0.74 mg AAE/g at 75°C compare to 77.67 ± 0.26 mg AAE/g at 25°C and 81.53 ± 0.68 mg AAE/g at 50°C. From DPPH assay results revealed that extraction temperature at 50°C has EC50 (p < 0.05) lowest value of 92.64 ± 0.56 µg/mL compared to G. crepioides extracted at 25°C (98.50 ± 1.18 µg/mL) and 75°C (101.72 ± 9.09 µg/mL). An excellent correlation exhibited between TAC and DPPH radical scavenging assays with r = 0.95 and r2 = 0.89. Present study reveals that UAE method with 70% ethanol, 60 minutes extraction time at 50°C temperature is an optimum to extract highest phenolic content and antioxidants from G. crepioides leaves. Conclusion: It was concluded from the study that extraction temperature would affect the extraction of phytochemicals from plants in turn it affects the biological activities.
Introduction: The mortality rate of glioma patients particularly with glioblastoma multiforme (GBM) remains high even with advancements in the multimodality treatment. This is partly due to chemoresistance of the glioma cells towards drug treatment which finally reduced the survival of GBM patients. In this study, we determined the chemosensitisation and oncogenic characteristics of ZFP36L2 in LN18 GBM cells using RNA interference (RNAi). Methods: Meta-analysis of microarray datasets was used to identify the druggable genes responsive to GBM chemosensitivity. Subsequently, the genes were validated using RNAi screening [pooled small interference RNA (siRNA)]. Temozolomide- resistant LN18 cells were used to evaluate the effects of gene silencing on chemosensitisation to the sub-lethal dose (1/10 of IC50) of temozolomide. Assays such as cell viability, proliferation, migration and invasion and apoptosis assays were carried out. The apoptosis pathway underlying chemosensitisation by ZFP36L2 siRNA was determined using a human apoptosis array kit. Statistical analyses were performed using one-way analysis of variance. Results: ZFP36L2 was identified as a potential marker of GBM based on the meta-analysis and RNAi screening. ZFP36L2 knockdown lead to 1) Apoptosis induction (p < 0.05) 2) Reduced cell migration (p < 0.05) 3) Reduced up to 82% of cell invasion (p < 0.01) and 4) Decreased cellular proliferation in siZFP36L2-treated LN18 cells. Downstream analysis showed that the sub-lethal dose of temozolomide caused major upregulation of BCL2-associated X, apoptosis regulator (BAX). Conclusion: ZFP36L2 is oncogenic and chemosensitive thus may contribute to gliomagenesis through cell proliferation, migration, invasion and apoptosis. RNAi therapy in combination with chemotherapy treatment such as temozolomide may serve as potential therapeutic approach in the future.
Introduction: In Malaysia, about 800 children are diagnosed with cancer, a globally a dreadful disease, each year, and osteosarcoma accounts for approximately 3% of such cancer. The early detection of the type and extent of bone cancer is important for effective management through surgery. But, the presence of soft tissue edema around a neoplasm can interfere with accurate local tumor staging and subsequent surgical planning. However very scanty research is done on this; none of the past studies focused specifically on the incidence and quantity of extraosseous edema and its impact. Our interdisciplinary retrospective study with objectives to study the presence of soft tissue edema adjacent to the tumors in the extremities, characterize their pattern and distribution involved 82 patients of wide range of age attending the Hospital Universiti Sains Malaysia with a histologically proven tumor or tumor-like lesion of bone. Methods: This paper emphasizes avoiding misinterpretation of such edema and subsequent over-staging of musculoskeletal tumor. We exclusively used 1T-Magnetic Resonance Imaging due to its excellent resolution. All cases were imaged (T1W, T2W, T1W fat suppressed Gadolinium enhanced, and STIR images) by using 1.5 Tesla MRI unit. STIR images permit study of larger volume of abnormal tissue than spin echo images. Results: Peritumoral edema in 5 cases, Paratumoral edema in 11 patients and mixed type in 45 cases were found including 10 benign tumors. Overall, 5 malignant lesions did not show any sift tissue edema! All the data were analyzed and interpretation and charecterisation of the edema was done by an experienced radiologist. The findings were correlated with histopathology examination results. Conclusion: In conclusion, accurate definition of the local extent of a bone tumor and exploration of soft tissue edema is required to maximize the success of diagnostic work-up and staging prior to biopsy and subsequent interventions while minimizing the amount of tissue removed.
Introduction: Short peptides have acquired increasing interest as promising therapeutics, particularly as anti-cancer alternatives during the recent years. They have been reported to demonstrate incredible anti-cancer potentials through targeting signalling transduction pathways, as well as modulation of cell cycle, tumour suppressor proteins and transcription factors. Peptides are primarily of interest due to its rapid kinetics, high potency and low biocompatibility issue. In search of novel anticancer leads, the main objective of this study is to evaluate the in-vitro antiproliferative properties of hybridized peptides against human hepatocellular carcinoma (HepG2) cells. Methods: Two series of hybridized peptides, ND and DN analogues were designed based on two parent peptides, NDC1 and NDC2, through fragments hybridization approach. Modification of amino acid residues at specific positions of NDC1 and NDC2 was done at the C-terminal. Then, MTT assay was performed to examine the antiproliferative ranging from 2-256µg/mL for 24 hours. Results: The parent peptide, NDC1 showed an IC50 value of 87±3.786 µg/mL at 24 hours while NDC2 did not display antiproliferative activity against HepG2 cells. ND1-4 showed higher toxicity against Vero cells compared to HepG2 cells while ND5 did not exhibit antiproliferative activities against both cell lines. In contrary, DN1 and DN4 was found to exhibit antiproliferative activity against HepG2 cells, with IC50 values 170±60.883µg/mL and 170±60.883µg/mL, respectively. Meanwhile, both these hybridized peptides showed minimal toxicity against Vero with IC50 values >256µg/mL. In contrast, DN2, DN3 and DN5 showed minimal antiproliferative activity against HepG2 with IC50 values >256µg/mL. Conclusion: Among the ND and DN hybridized peptides, two hybridized peptides, DN1 and DN5, showed potential anti-proliferative activities against HepG2 with minimal toxicity against Vero. Nevertheless, their activity has been diminished as compared to NDC1 and hence, can be further improved.
Introduction: In an on-going research, the endophyte Aspergillus sp. HAB10R12 have been selected for detailed chemical investigation after its crude ethyl acetate extract showed promising anticancer properties with high selectivity. Methods: The former was determined on two cancer cell lines namely, HCT116 and MCF-7 (IC50 = 0.05 and 0.04 μg/mL, respectively) and one non-tumor cell line HeLa (IC50 = 10.5 μg/mL). Results: The result indicates the secondary metabolites produced by the fungus are 200 folds more selective towards cancer cells over normal cells, calling for an immediate detailed investigation of their composition. Preliminary chemical analysis of the crude extract using LC-MS, NMR and UHPLC-UV showed the presence of an uncommon group of diterpene pyrones (NF00659 A1, B1 and A3), previously isolated once with only partial characterization reported. Consequently, large scale isolation of secondary metabolites was carried out and led to the identification of four of the previously isolated diterpene pyrones. Conclusion: The isolation, characterization, relative stereochemistry analysis, and a plausible biosynthesis of the diterpene pyrone compounds is presented herein.
Introduction: Copper complexes can be developed as targeted agent for cancer due to increased uptake of copper by cancer cells for angiogenesis. Our previous published data showed that copper complex Cu(SBCM)2 induced apoptosis towards triple-negative MDA-MB-231 breast cancer cells. However, its effect towards other breast cancer subtype remains unknown. Current study was performed to explore the cytotoxicity of Cu(SBCM)2 towards oestrogen- receptor positive MCF-7 breast cancer cells. Methods: MTT assay was employed to study the growth inhibition of Cu(SBCM)2 towards MCF-7 breast cancer cells and human non-cancerous MCF10A breast cells. Morphological changes of Cu(SBCM)2-treated MCF-7 cells was observed under inverted light microscope. Induction of cell cycle arrest and apoptosis were accessed by flow cytometry. The expression of wild-type p53 protein was evaluated by western blotanalysis. Intracellular reactive oxygen species of MCF-7 treated with Cu(SBCM)2 was detected using DCFHDA assay. The cells were then co-treated with Cu(SBCM)2 and antioxidants to evaluate the involvement of ROS in the cytotoxicity of Cu(SBCM)2. Molecular docking study was performed to determine the interaction of Cu(SBCM)2 with DNA, DNA topoisomerase I, and human ribonucleotide reductase. Results: Cu(SBCM)2 induced G2/M phase cell cycle arrest and apoptosis in MCF-7 cells possibly via upregulation of p53 wild-type protein. Cu(SBCM)2 was less toxic towards MCF10A cells. Increased level of intracellular ROS was not detected in MCF-7 cells after treatment with Cu(SBCM)2. However, N-acetylcysteine antioxidant enhance the cytotoxicity of Cu(SBCM)2 in MCF-7 cells. Cu(SBCM)2 showed the greatest affinity for DNA topoisomerase I in comparison to DNA and human ribonucleotide reductase. Conclusions: Cu(SBCM)2 has a potential to be developed as a targeted agent for breast cancer.
Introduction: Colorectal cancer is the second most common cause of death in women, and the third most common cause in men. The main treatments available following surgery are chemotherapy and radiotherapy which are not always effective and have side effects. Modern medicine aims to develop targeted cancer therapies that are efficient and cause less side effects to patients. However, this approach requires a thorough understanding of the molecular events that cause cancer cell to grow and divide in order to identify suitable targets. The process of translating the findings into clinical studies can be high cost and technically demanding. However, development of a tissue microarray (TMA), allows immunohistochemical (IHC) staining of multiple cases simultaneously, thereby greatly reducing costs and time. Methods: A TMA was produced from approximately 400 cases of colorectal cancer, along with collection of associated clinical and pathological data. Sections from the TMA were tested for quality by staining with haematoxylin and eosin (H & E), in addition to IHC markers to molecularly classify the colon cancers. Results: The cores from the 384 cases of cancer were successfully transferred to 18 recipient TMA blocks. H & E staining showed good morphological preservation of the cases, reflecting the tumour in the donor blocks. IHC testing was able to successfully classify cases into distinct molecular groupings. Conclusions: The development of a TMA of colorectal cancers provides a valuable tool for the efficient and subsequent molecular classification of colorectal cancer using immunohistochemistry.
Introduction: Hepatic radioembolization is a minimally invasive procedure involving intrarterial administration of radioembolic microspheres for the treatment of liver tumours. In this study, a biocompatible polystyrene (PS) microspheres formulation containing radioactive Samarium-153 (153Sm) was synthesized and tested. The 153Sm emits both diagnostic gamma energy and therapeutic beta radiation, renders the synthesized microspheres an ideal theranostic radioembolic agent for hepatic radioembolization. Methods: First, the 152Sm2O3 (20 – 50%, w/v) was encapsulated in PS microspheres using solid-in-oil-in-water solvent evaporation method. The 152Sm-labelled PS microspheres were then activated to 153Sm (Eβmax = 807.6 keV, half-life = 46.3 hours) via 152Sm (n,γ) 153Sm reaction in a nuclear reactor with a neutron flux of 2.0 x 1012 n.cm-2.s-1. Physicochemical characterization, gamma spectroscopy and in-vitro radiolabeling studies were carried out to study the properties and stability of the microspheres before and after neutron activation. Results: The 153Sm -labelled PS microspheres achieved a nominal activity of 4.0 GBq.g-1 after 6 hours of neutron activation. Scanning electron microscope (SEM) and particle size analysis show that the microspheres remained spherical with diameters within 15 – 60 μm after neutron activation. No long half-life radioimpurities were found in the samples as revealed by the gamma spectroscopy results. The 153Sm-labelled PS microspheres achieved radiolabeling efficiency of more than 95% in saline and blood plasma over 480 hours. Conclusion: A biocompatible 153Sm-radiolabelled PS microspheres formulation has been successfully developed. The formulation achieved desirable properties for theranostic treatment of liver tumours. The formulation is relatively cheaper, easier to be produced and more readily available.
Introduction: The Hedgehog (Hh) pathway serves as a major regulator in organ development, stem cell maintenance, cell proliferation, and cell differentiation. This pathway is highly regulated and aberrant activation will promote tumorigenesis. Hh pathway notably Sonic Hedgehog pathway was reported to be upregulated and promote tumorigenesis in various human malignancies including colorectal, gastric, lung, prostate, and breast. This review was aimed to discuss the current understanding of Hh pathway activation in different types of human cancers and discuss the development of the therapeutic applications targeting Hh pathway. Methods: A systematic review was conducted using the electronic research database PubMed Central (PMC) from 2014-2019. The search was limited to studies that are relevant to both Hh signalling pathway and human cancers. A total of 50 articles were selected and their references cited were searched and reviewed. Results: The results regarding the role of Hh signalling in pancreatic cancer and colorectal cancer are controversial with some reporting tumor promoting activities whereas others tumor suppressive activity. Besides, results from other studies suggesting that Hh signalling pathway plays an oncogenic role by inducing tumor cells proliferation, promoting metastasis and maintaining cancer stem cells in human cancers such as lung, stomach, and breast. To date, Glasdegib (PF-04449913) is the only Hh targeting small molecule inhibitor being studied at FDA Phase 3 clinical trial. Identification of the right tumors and minimization of the side effects remain as the main obstacles in the development of Hh signalling inhibitors. Conclusion: In conclusion, advancement in our understanding of Hh pathway has provided us opportunity to develop novel therapeutic strategies to fight human cancers with activated Hh pathway but more studies need to be conducted to solve the controversial regarding the role of Hh pathway in certain cancers.