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A Comparison between the Online Prognostic Tool PREDICT and myBeST for Women with Breast Cancer in Malaysia

Nik Ab Kadir MN, Mohd Hairon S, Ab Hadi IS, Yusof SN, Muhamat SM, Yaacob NM

Cancers (Basel), 2023 Mar 30;15(7).
PMID: 37046725 DOI: 10.3390/cancers15072064

The PREDICT breast cancer is a well-known online calculator to estimate survival probability. We developed a new prognostic model, myBeST, due to the PREDICT tool's limitations when applied to our patients. This study aims to compare the performance of the two models for women with breast cancer in Malaysia. A total of 532 stage I to III patient records who underwent surgical treatment were analysed. They were diagnosed between 2012 and 2016 in seven centres. We obtained baseline predictors and survival outcomes by reviewing patients' medical records. We compare PREDICT and myBeST tools' discriminant performance using receiver-operating characteristic (ROC) analysis. The five-year observed survival was 80.3% (95% CI: 77.0, 83.7). For this cohort, the median five-year survival probabilities estimated by PREDICT and myBeST were 85.8% and 82.6%, respectively. The area under the ROC curve for five-year survival by myBeST was 0.78 (95% CI: 0.73, 0.82) and for PREDICT was 0.75 (95% CI: 0.70, 0.80). Both tools show good performance, with myBeST marginally outperforms PREDICT discriminant performance. Thus, the new prognostic model is perhaps more suitable for women with breast cancer in Malaysia.
The role of Candida albicans candidalysin ECE1 gene in oral carcinogenesis

Engku Nasrullah Satiman EAF, Ahmad H, Ramzi AB, Abdul Wahab R, Kaderi MA, Wan Harun WHA, et al.

J Oral Pathol Med, 2020 Oct;49(9):835-841.
PMID: 32170981 DOI: 10.1111/jop.13014

Oral squamous cell carcinoma is associated with many known risk factors including tobacco smoking, chronic alcoholism, poor oral hygiene, unhealthy dietary habits and microbial infection. Previous studies have highlighted Candida albicans host tissue infection as a risk factor in the initiation and progression of oral cancer. C albicans invasion induces several cancerous hallmarks, such as activation of proto-oncogenes, induction of DNA damage and overexpression of inflammatory signalling pathways. However, the molecular mechanisms behind these responses remain unclear. A recently discovered fungal toxin peptide, candidalysin, has been reported as an essential molecule in epithelial damage and host recognition of C albicans infection. Candidalysin has a clear role in inflammasome activation and induction of cell damage. Several inflammatory molecules such as IL-6, IL-17, NLRP3 and GM-CSF have been linked to carcinogenesis. Candidalysin is encoded by the ECE1 gene, which has been linked to virulence factors of C albicans such as adhesion, biofilm formation and filamentation properties. This review discusses the recent epidemiological burden of oral cancer and highlights the significance of the ECE1 gene and the ECE1 protein breakdown product, candidalysin in oral malignancy. The immunological and molecular mechanisms behind oral malignancy induced by inflammation and the role of the toxic fungal peptide candidalysin in oral carcinogenesis are explored. With increasing evidence associating C albicans with oral carcinoma, identifying the possible fungal pathogenicity factors including the role of candidalysin can assist in efforts to understand the link between C albicans infection and carcinogenesis, and pave the way for research into therapeutic potentials.
Enhanced Mechanical and Thermal Properties of Modified Oil Palm Fiber-Reinforced Polypropylene Composite via Multi-Objective Optimization of In Situ Silica Sol-Gel Synthesis

Mat Rozi N, Hamid HA, Hossain MS, Khalil NA, Ahmad Yahaya AN, Syimir Fizal AN, et al.

Polymers (Basel), 2021 Sep 29;13(19).
PMID: 34641152 DOI: 10.3390/polym13193338

A multi-objective optimization of in situ sol-gel process was conducted in preparing oil palm fiber-reinforced polypropylene (OPF-PP) composite for an enhancement of mechanical and thermal properties. Tetraethyl orthosilicate (TEOS) and butylamine were used as precursors and catalysts for the sol-gel process. The face-centered central composite design (FCCD) experiments coupled with response surface methodology (RSM) has been utilized to optimize in situ silica sol-gel process. The optimization process showed that the drying time after the in-situ silica sol-gel process was the most influential factor on silica content, while the molar ratio of TEOS to water gave the most significant effect on silica residue. The maximum silica content of 34.1% and the silica residue of 35.9% were achieved under optimum conditions of 21.3 h soaking time, 50 min drying time, pH value of 9.26, and 1:4 molar ratio of TEOS to water. The untreated oil palm fiber (OPF) and silica sol-gel modified OPF (SiO2-OPF) were used as the reinforcing fibers, with PP as a matrix and maleic anhydride grafted polypropylene (MAgPP) as a compatibilizer for the fiber-reinforced PP matrix (SiO2-OPF-PP-MAgPP) composites preparation. The mechanical and thermal properties of OPF-PP, SiO2-OPF-PP, SiO2-OPF-PP-MAgPP composites, and pure PP were determined. It was found that the OPF-S-PP-MAgPP composite had the highest toughness and stiffness with values of tensile strength, Young's modulus, and elongation at break of 30.9 MPa, 881.8 MPa, and 15.1%, respectively. The thermal properties analyses revealed that the OPF-S-PP-MAgPP exhibited the highest thermally stable inflection point at 477 °C as compared to pure PP and other composites formulations. The finding of the present study showed that the SiO2-OPF had the potential to use as a reinforcing agent to enhance the thermal-mechanical properties of the composites.
Cell membrane cloaked nanomedicines for bio-imaging and immunotherapy of cancer: Improved pharmacokinetics, cell internalization and anticancer efficacy

Hussain Z, Rahim MA, Jan N, Shah H, Rawas-Qalaji M, Khan S, et al.

J Control Release, 2021 07 10;335:130-157.
PMID: 34015400 DOI: 10.1016/j.jconrel.2021.05.018

Despite enormous advancements in the field of oncology, the innocuous and effectual treatment of various types of malignancies remained a colossal challenge. The conventional modalities such as chemotherapy, radiotherapy, and surgery have been remained the most viable options for cancer treatment, but lacking of target-specificity, optimum safety and efficacy, and pharmacokinetic disparities are their impliable shortcomings. Though, in recent decades, numerous encroachments in the field of onco-targeted drug delivery have been adapted but several limitations (i.e., short plasma half-life, early clearance by reticuloendothelial system, immunogenicity, inadequate internalization and localization into the onco-tissues, chemoresistance, and deficient therapeutic efficacy) associated with these onco-targeted delivery systems limits their clinical viability. To abolish the aforementioned inadequacies, a promising approach has been emerged in which stealthing of synthetic nanocarriers has been attained by cloaking them into the natural cell membranes. These biomimetic nanomedicines not only retain characteristics features of the synthetic nanocarriers but also inherit the cell-membrane intrinsic functionalities. In this review, we have summarized preparation methods, mechanism of cloaking, and pharmaceutical and therapeutic superiority of cell-membrane camouflaged nanomedicines in improving the bio-imaging and immunotherapy against various types of malignancies. These pliable adaptations have revolutionized the current drug delivery strategies by optimizing the plasma circulation time, improving the permeation into the cancerous microenvironment, escaping the immune evasion and rapid clearance from the systemic circulation, minimizing the immunogenicity, and enabling the cell-cell communication via cell membrane markers of biomimetic nanomedicines. Moreover, the preeminence of cell-membrane cloaked nanomedicines in improving the bio-imaging and theranostic applications, alone or in combination with phototherapy or radiotherapy, have also been pondered.
Fulltext myBeST-A Web-Based Survival Prognostic Tool for Women with Breast Cancer in Malaysia: Development Process and Preliminary Validation Study

Nik Ab Kadir MN, Mohd Hairon S, Yaacob NM, Yusof SN, Musa KI, Yahya MM, et al.

Int J Environ Res Public Health, 2023 Feb 08;20(4).
PMID: 36833678 DOI: 10.3390/ijerph20042985

Women with breast cancer are keen to know their predicted survival. We developed a new prognostic model for women with breast cancer in Malaysia. Using the model, this study aimed to design the user interface and develop the contents of a web-based prognostic tool for the care provider to convey survival estimates. We employed an iterative website development process which includes: (1) an initial development stage informed by reviewing existing tools and deliberation among breast surgeons and epidemiologists, (2) content validation and feedback by medical specialists, and (3) face validation and end-user feedback among medical officers. Several iterative prototypes were produced and improved based on the feedback. The experts (n = 8) highly agreed on the website content and predictors for survival with content validity indices ≥ 0.88. Users (n = 20) scored face validity indices of more than 0.90. They expressed favourable responses. The tool, named Malaysian Breast cancer Survival prognostic Tool (myBeST), is accessible online. The tool estimates an individualised five-year survival prediction probability. Accompanying contents were included to explain the tool's aim, target user, and development process. The tool could act as an additional tool to provide evidence-based and personalised breast cancer outcomes.
Fulltext Development of Predictive Models for Survival among Women with Breast Cancer in Malaysia

Nik Ab Kadir MN, Yaacob NM, Yusof SN, Ab Hadi IS, Musa KI, Mohd Isa SA, et al.

Int J Environ Res Public Health, 2022 Nov 20;19(22).
PMID: 36430052 DOI: 10.3390/ijerph192215335

Prediction of survival probabilities based on models developed by other countries has shown inconsistent findings among Malaysian patients. This study aimed to develop predictive models for survival among women with breast cancer in Malaysia. A retrospective cohort study was conducted involving patients who were diagnosed between 2012 and 2016 in seven breast cancer centres, where their survival status was followed until 31 December 2021. A total of 13 predictors were selected to model five-year survival probabilities by applying Cox proportional hazards (PH), artificial neural networks (ANN), and decision tree (DT) classification analysis. The random-split dataset strategy was used to develop and measure the models' performance. Among 1006 patients, the majority were Malay, with ductal carcinoma, hormone-sensitive, HER2-negative, at T2-, N1-stage, without metastasis, received surgery and chemotherapy. The estimated five-year survival rate was 60.5% (95% CI: 57.6, 63.6). For Cox PH, the c-index was 0.82 for model derivation and 0.81 for validation. The model was well-calibrated. The Cox PH model outperformed the DT and ANN models in most performance indices, with the Cox PH model having the highest accuracy of 0.841. The accuracies of the DT and ANN models were 0.811 and 0.821, respectively. The Cox PH model is more useful for survival prediction in this study's setting.
Fulltext Recent Advancements in Stimuli Responsive Drug Delivery Platforms for Active and Passive Cancer Targeting

Rahim MA, Jan N, Khan S, Shah H, Madni A, Khan A, et al.

Cancers (Basel), 2021 Feb 07;13(4).
PMID: 33562376 DOI: 10.3390/cancers13040670

The tumor-specific targeting of chemotherapeutic agents for specific necrosis of cancer cells without affecting the normal cells poses a great challenge for researchers and scientists. Though extensive research has been carried out to investigate chemotherapy-based targeted drug delivery, the identification of the most promising strategy capable of bypassing non-specific cytotoxicity is still a major concern. Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis. This review focuses on the physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems for triggered cancer chemotherapy through active and/or passive targeting. Moreover, the review also provided a brief insight into the molecular dynamic simulations associated with stimuli-based tumor targeting.
Fulltext Comparing Low Volume Versus Conventional Volume of Polyethylene Glycol for Bowel Preparation during Colonoscopy: A Randomised Controlled Trial

Othman MF, Zakaria AD, Yahya MM, Md Hashim MN, Wan Mokhter WM, Wan Zain WZ, et al.

Malays J Med Sci, 2023 Oct;30(5):106-115.
PMID: 37928791 DOI: 10.21315/mjms2023.30.5.9

BACKGROUND: Polyethylene glycol (PEG) solution is widely used as a colonoscopic bowel cleaning agent, although some patients are intolerant due to the need for ingesting large solution volumes and unpleasant taste. A low-volume solution may enhance patient tolerability and compliance in bowel preparation. Accordingly, this study compared the effectiveness of two difference PEG volumes for bowel preparation before colonoscopy in terms of bowel cleanliness, completeness of colonoscopy, patient tolerability and colonoscopy duration.
METHODS: Using a prospective randomised controlled single-blinded study design, 164 patients scheduled for colonoscopy were allocated to two groups (n = 82 patients in each) to receive either the conventional PEG volume (3 L, control group) or the low volume (2 L, intervention group). The Boston Bowel Preparation Scale (BBPS), a validated scale for assessing bowel cleanliness during colonoscopy, was used to score bowel cleanliness in three colon segments. Secondarily, colonoscopy completeness, tolerability to drinking PEG and the duration of colonoscopy were compared between the groups.
RESULTS: There were no statistically significant differences between the two intervention groups in terms of bowel cleanliness (P = 0.119), colonoscopy completion (P = 0.535), tolerability (P = 0.190) or the amount of sedation/analgesia required (midazolam, P = 0.162; pethidine, P = 0.708). Only the duration of colonoscopy differed between the two groups (longer duration in the control group, P = 0.039).
CONCLUSION: Low-volume (2 L) PEG is as effective as the standard 3 L solution in bowel cleaning before colonoscopy; however, the superiority of either solution could not be established.