myBeST-A Web-Based Survival Prognostic Tool for Women with Breast Cancer in Malaysia: Development Process and Preliminary Validation Study.

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.

Development of Predictive Models for Survival among Women with Breast Cancer in Malaysia.

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.

Association between c-Myc Expression with Clinicopathological Features in T And NK Cell Lymphomas.

BACKGROUND: c-Myc has become significantly involved in aggressive B-cell non Hodgkin lymphoma (NHL), but little is known about its importance in T and NK cell NHL (TNKcNHLs) in association with prognostic factors. The study is to investigate the significance of c-Myc expression with clinicopathological features of TNKcNHLs patients. METHODOLOGY: A cross-sectional study of 32 archived tissue blocks of TNKcNHLs were immunohistochemically stained with c-Myc. The results were microscopically evaluated and statistically analysed to examine the association between the clinicopathological data with the c-Myc expression. RESULTS: c-Myc protein expressions were detected in 25/32 (78.1%) cases. The median age was 38-years.  Malay ethnicity (92.0%) with 21 males and 11 females. c-Myc expressions were seen in T lymphoblastic lymphoma (20%), ALK-positive ALCL (16%) ,PTCL,NOS (16%), extra nodal NK/T-cell lymphoma, nasal type (12%), extra-nodal involvement (78.1%), elevated serum LDH (83.3%) and high ECOG performance status (82.4%). However, no statistical significant of c-Myc in association with the clinicopathological parameters (p > 0.05). CONCLUSION: There was no statistically significant association of clinicopathological parameters and histological subtypes of TNKcNHLs contributed by small samples tested. However, the attribution of c-Myc in this disease should be further explored.

Human umbilical cord mesenchymal stem cell-derived extracellular vesicles ameliorate airway inflammation in a rat model of chronic obstructive pulmonary disease (COPD).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin. METHODS: In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student's t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD). RESULTS: Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. CONCLUSIONS: In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.

ADAM9 Expression in Uterine Cervical Cancer and Its Associated Factors

Background: Cervical cancer is a preventable disease caused by human papillomaviruses. It is the third most common cancer to occur in women of reproductive age. The ADAM9 protein plays a role in basement membrane degradation and tumour metastasis in certain types of tumour. Thus, it has the potential to become a new targeted therapy. The objective of this study was to investigate ADAM9 expression in cervical cancer and to determine the factors associated with ADAM9-positive expression. Methods: This cross-sectional study was conducted in Hospital Universiti Sains Malaysia (HUSM) Kelantan, Malaysia from December 2010 to December 2012. Histological slides obtained from 95 cervical cancer cases diagnosed and/or treated in HUSM from 2000 to 2010 were analysed. The ADAM9 immunostain was then performed on the paraffin blocks. The statistical data entry and analysis were done using SPSS version 18.0. Multiple logistic regression analysis was performed to determine the factors associated with ADAM9-positive expression. Result: Of the 95 cervical cancer patients included in the study, 72 (75.8%) patients showed positive ADAM9 expression. The mean age of the patients was 53.89 (10.83) years old. Squamous cell carcinoma was the most common type of cervical cancer (n = 67, 70.5%). Factors that showed a statistically significant association with ADAM9-positive expression were tumour size (adjusted odds ratio [adj. OR]: 1.08; 95% confidence interval [CI]: 1.02, 1.13; p = 0.004), distant metastasis (adj. OR: 12.82; 95% CI: 1.91, 86.13; p = 0.009) and the histological type of cervical cancer (i.e. squamous cell carcinoma) (adj. OR: 7.39; 95% CI: 1.42, 38.51; p = 0.017). Conclusion: The ADAM9 immunostain was consistently positive in malignant cells. Thus, ADAM9 expression can be used as a prognostic/therapeutic indicator in aiding clinician decision-making regarding patient treatment (targeted therapy).