Materials and methods: 3D-mediated inhibition on cell viability was evaluated by MTT and real-time cell proliferation was measured by xCelligence RTDP instrument. Western blotting was used to measure pro-apoptotic, anti-apoptotic proteins and JAK2-STAT3 phosphorylation. Flow cytometry was used to measure ROS production and apoptosis.
Results: Our study revealed that 3D treatment significantly reduced the viability of human CRC cells HT-29 and SW620. Furthermore, 3D treatment induced the generation of reactive oxygen species (ROS) in human CRC cells. Confirming our observation, N-acetylcysteine significantly inhibited apoptosis. This is further evidenced by the induction of p53 and Bax; release of cytochrome c; activation of caspase-9, caspase-7 and caspase-3; and cleavage of PARP in 3D-treated cells. This compound was found to have a significant effect on the inhibition of antiapoptotic proteins Bcl2 and BclxL. The results further demonstrate that 3D inhibits JAK2-STAT3 pathway by decreasing the constitutive and IL-6-induced phosphorylation of STAT3. 3D also decreases STAT3 target genes such as cyclin D1 and survivin. Furthermore, a combination study of 3D with doxorubicin (Dox) also showed more potent effects than single treatment of Dox in the inhibition of cell viability.
Conclusion: Taken together, these findings indicate that 3D induces ROS-mediated apoptosis and inhibits JAK2-STAT3 signaling in CRC.
METHODS: Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to genotype all the aforementioned gene polymorphisms. Kaplan-Meier survival function, log-rank test and Cox regression were used to investigate the effect of gene polymorphisms on the all-cause survival of NPC.
RESULTS: NPC cases carrying T/T genotype of ITGA2 C807T have poorer all-cause survival compared to those with C/C genotypes, with an adjusted HR of 2.06 (95% CI = 1.14-3.72) in individual model. The 5-year survival rate of C/C carriers was 55% compared to those with C/T and T/T where the survival rates were 50% and 43%, respectively.
CONCLUSION: The finding from the present study showed that ITGA2 C807T polymorphism could be potentially useful as a prognostic biomarker for NPC. However, the prognostic value of ITGA2 C807T polymorphism has to be validated by well-designed further studies with larger patient numbers.
METHODS: Data from 585 eligible patients who received palliative radiotherapy between January 2012 and December 2014 were analysed. Median overall survival was calculated from the commencement of first fraction of the last course of radiotherapy to date of death or when censored. 30-DM was calculated as the proportion of patients who died within 30 days from treatment start date. Kaplan-Meier survival analysis was used to estimate survival. Chi-square test and logistic regression was used to assess the impact of potential prognostic factors on median survival and 30-DM.
RESULTS: The most common diagnoses were lung and breast cancers and most common irradiated sites were bone and brain. Median survival and 30-DM were 97 days and 22.7% respectively. Primary cancer, age, treatment course, performance status, systemic treatment post radiotherapy and intended radiotherapy treatment completed had an impact on median survival whereas mainly the latter three factors had an impact on 30-DM.
CONCLUSION: Median survival and factors affecting both survival and 30-DM in our study are comparable to others. However, a 30-DM rate of 22.7% is significantly higher compared to the literature. We need to better select patients who will benefit from palliative radiotherapy in our centre.
METHODS: This is a retrospective study examining CRC data for the period 2007 to 2017 retrieved from a population based cancer registry in Brunei Darussalam. A total of 728 patients were included in the analysis. Kaplan Meier method was used to estimate survival rates. Univariate analysis using log-rank test was used to examine the differences in survival between groups. Multivariate analysis using Cox PH regression was used to estimate hazard of death and obtain significant predictors that influence CRC patients' survival.
RESULTS: The median survival time for colorectal, colon and rectal cancer patients were 57.0, 85.8 and 40.0 months respectively. The overall 1-, 3- and 5- year survival rates for CRC patients were 78.0%, 57.7% and 49.6% respectively. In univariate analysis, age at diagnosis, ethnicity, cancer stage, tumour location and histology were found to have significant difference in CRC patients' survival. In the Cox PH analysis, older age (≥70 years), cancer stage, ethnicity and other histological type were determined as associated factors of CRC patients' survival.
CONCLUSION: This study found the overall 5-year survival rate of CRC in Brunei Darussalam is similar to that in some Asian countries such as Singapore and Malaysia. However, more efforts need to be carried out in order to raise awareness of CRC and improve the survival of CRC patients.
METHOD: Retrospective study of children with ANE seen at University of Malaya Medical Centre from 2014 to 2019. All clinical details including ANE-severity score (ANE-SS), immunomodulation treatment and neurodevelopmental long-term outcome were collected.
RESULTS: Thirteen patients had ANE and brainstem death occurred in 5. In 10 patients (77%) viruses were isolated contributing to ANE: 8 influenza virus, 1 acute dengue infection, and 1 acute varicella zoster infection. The ANE-SS ranged 2-7: 9 were high risk and 4 were medium risk. Among the 8 survivors; 1 was lost to follow-up. Follow-up duration was 1-6 years (median 2.2). At follow-up among the 4 high-risk ANE-SS: 2 who were in a vegetative state, 1 remained unchanged and 1 improved to severe disability; the other 2 with severe disability improved to moderate and mild disability respectively. At follow-up all 3 medium-risk ANE-SS improved: 2 with severe disability improved to moderate and mild disability respectively, while 1 in a vegetative state improved to severe disability. Early treatment with immunomodulation did not affect outcome.
CONCLUSION: Our ANE series reiterates that ANE is a serious cause of encephalopathy with mortality of 38.5%. All survivors were in a vegetative state or had severe disability at discharge. Most of the survivors made a degree of recovery but good recovery was seen in 2. Follow-up of at least 12 months is recommended for accurate prognostication. Dengue virus infection needs to be considered in dengue endemic areas.
METHODS: The designed nano- anticancer formulation was characterized thorough X-ray diffraction (XRD), Fourier transformed infrared (FTIR), transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) and Brunauer-Emmett-Teller (BET) methods. The nano- anticancer formulation (DTX- CaCO3NP) was evaluated for drug delivery properties thorough in vitro release study in human body simulated solution at pH 7.4 and intracellular lysosomal pH 4.8.
RESULTS: Characterization revealed the successful synthesis of DTX- CaCO3NP, which had a sustained release at pH 7.4. TEM showed uniformly distributed pleomorphic shaped pure aragonite particles. The highest entrapment efficiency (96%) and loading content (11.5%) were obtained at docetaxel to nanoparticles ratio of 1:4. The XRD patterns revealed strong crystallizations in all the nanoparticles formulation, while FTIR showed chemical interactions between the drug and nanoparticles with negligible positional shift in the peaks before and after DTX loading. BET analysis showed similar isotherms before and after DTX loading. The designed DTX- CaCO3NP had lower (p 0.05) effects at 48 h and 72 h. However, the DTX- CaCO3NP released less than 80% of bond DTX at 48 and 72 h but showed comparable effects with free DTX.
CONCLUSIONS: The results showed that the developed DTX- CaCO3NP released DTX slower at pH 7.4 and had comparable cytotoxicity with free DTX at 48 and 72 h in MCF-7 cells.