METHODS: Smaller micro tissues (˂150 μm in diameter) mixed with Matrigel were engrafted subcutaneously into NSG mice to generate the passage 1 (P1) patient-derived xenograft. The micro tumours from P1 patient-derived xenograft were then excised and orthotopically xenografted into another batch of NSG mice to generate a metastatic colorectal cancer patient-derived xenograft, P2. Haematoxylin and eosin and immunohistochemistry staining were performed to compare the characters between patient-derived xenograft tumours and primary tumours.
RESULTS: About 16 out of 18 P1 xenograft models successfully grew a tumour for 50.8 ± 5.1 days (success rate 89.9%). Six out of eight P1 xenograft models originating from metastatic patients successfully grew tumours in the colon and metastasized to liver or lung in the NSG recipients for 60.9 ± 4.5 days (success rate 75%). Histological examination of both P1 and P2 xenografts closely resembled the histological architecture of the original patients' tumours. Immunohistochemical analysis revealed similar biomarker expression levels, including CDH17, Ki-67, active β-catenin, Ki-67 and α smooth muscle actin when compared with the original patients' tumours. The stromal components that support the growth of patient-derived xenograft tumours were of murine origin.
CONCLUSIONS: Metastatic patient-derived xenograft mouse model could be established with shorter time and higher success rate. Although the patient-derived xenograft tumours were supported by the stromal cells of murine origin, they retained the dominant characters of the original patient tumours.
METHOD: Relevant studies detecting the expression or SNP of CYP24A1 in cancer patients up till May 2022 were systematically searched in four common scientific databases including PubMed, EMBASE, Cochrane library and ISI Web of Science. The pooled hazard ratios (HRs) indicating the ratio of hazard rate of survival time between CYP24A1high population vs CYP24A1low population were calculated. The pooled HRs and odds ratios (ORs) with 95% confidence intervals (CIs) were used to explore the association between CYP24A1's expression or SNP with survival, metastasis, recurrence, and drug resistance in cancer patients.
RESULT: Fifteen studies were included in the meta-analysis after an initial screening according to the inclusion and exclusion criteria. There was a total of 3784 patients pooled from all the included studies. Results indicated that higher expression or SNP of CYP24A1 was significantly correlated with shorter survival time with pooled HRs (95% CI) of 1.21 (1.12, 1.31), metastasis with pooled ORs (95% CI) of 1.81 (1.11, 2.96), recurrence with pooled ORs (95% CI) of 2.14 (1.45, 3.18) and drug resistance with pooled HRs (95% CI) of 1.42 (1.17, 1.68). In the subgroup analysis, cancer type, treatment, ethnicity, and detection approach for CYP24A1 did not affect the significance of the association between CYP24A1 expression and poor prognosis.
CONCLUSION: Findings from our meta-analysis demonstrated that CYP24A1's expression or SNP was correlated with cancer progression and drug resistance. Therefore, CYP24A1 could be a potential molecular marker for cancer resistance.
OBJECTIVE: Ternary copper (II) complex incorporated with 1-10-phenanthroline and L-tyrosine was investigated for its anti-cancer effects in HT-29 colorectal cancer cells.
METHODS: Cytotoxic effects of ternary copper (II) complex in HT-29 cells were evaluated using MTT assay, Real-Time Cell Analysis (RTCA), and lactate dehydrogenase (LDH) assay. Cell cycle analysis was performed using flow cytometry. Apoptosis induction was studied by Annexin V-FITC/propidium iodide (PI) staining and mitochondrial membrane potential analysis (JC-10 staining) using flow cytometry. Intracellular reactive oxygen species (ROS) were detected by DCFH-DA assay. The expression of proteins involved in the apoptotic signalling pathway (p53, caspases, and PARP-1) was evaluated by western blot analysis.
RESULTS: Ternary copper (II) complex reduced the cell viability of HT-29 cells in a time- and dose-dependent manner, with IC50 of 2.4 ± 0.4 and 0.8 ± 0.04 µM at 24 and 48 hours, respectively. Cell cycle analysis demonstrated induction of S-phase cell cycle arrest. Morphological evaluation and Annexin V-FITC/PI flow cytometry analysis confirmed induction of apoptosis that was further supported by cleavage and activation of caspase-8, caspase-9, caspase-3, and PARP-1. Mutant p53 was also downregulated in a dose-dependent manner. No LDH release, mitochondrial membrane potential disruption, and ROS production were observed.
CONCLUSION: Ternary copper (II) complex holds great potential to be developed for colorectal cancer treatment.
METHODS: Nine full-text articles in English that reported the clinical and radiological outcomes of KA TKA were included. Five studies had a control group of patients who underwent MA TKA. Data on patient demographics, clinical scores, and radiological results were extracted. There were two level I, one level II, three level III, and three level IV studies. Six of the nine studies used patient-specific instrumentation, one study used computer navigation, and two studies used manual instrumentation.
RESULTS: The clinical outcomes of KA TKA were comparable or superior to those of MA TKA with a minimum 2-year follow-up. Limb and knee alignment in KA TKA was similar to those in MA TKA, and component alignment showed slightly more varus in the tibial component and slightly more valgus in the femoral component. The JLOA in KA TKA was relatively parallel to the floor compared to that in the native knee and not oblique (medial side up and lateral side down) compared to that in MA TKA. The implant survivorship and complication rate of the KA TKA were similar to those of the MA TKA.
CONCLUSION: Similar or better clinical outcomes were produced by using a KA TKA at early-term follow-up and the component alignment differed from that of MA TKA. KA TKA seemed to restore function without catastrophic failure regardless of the alignment category up to midterm follow-up. The JLOA in KA TKA was relatively parallel to the floor similar to the native knee compared to that in MA TKA. The present review of nine published studies suggests that relatively new kinematic alignment is an acceptable and alternative alignment to mechanical alignment, which is better understood. Further validation of these findings requires more randomized clinical trials with longer follow-up.
LEVEL OF EVIDENCE: Level II.
METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases).
RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk.
CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry.
METHODS: Data were retrospectively extracted from all the Chemotherapy Return Forms in 2016, which is a compulsory documentation accompanying each return of parenteral chemotherapy regimen. The following data were extracted: patient's diagnosis, gender, location of treatment (i.e. ward/daycare clinic), start date of chemotherapy regimen, type of cytotoxic drug returned, dose of cytotoxic drug returned, number of cytotoxic drug preparations returned and reason for return as well as whether the returned cytotoxic drug preparations could be re-dispensed. The cost of wastage was calculated based on the cost per mg (or per unit) of the particular returned cytotoxic drug.
RESULTS: One hundred and fifty-nine cases of returned chemotherapy regimen comprising of 231 parenteral cytotoxic drug preparations were analysed. The total cost of returned chemotherapy regimen for 2016 was €3632, with €756 (20.8%) worth of chemotherapy regimens returned due to preventable reasons and €2876 (79.2%) worth of chemotherapy regimens returned due to non-preventable reasons. Approximately 50% of cases returned chemotherapy regimen were due to deterioration of patient's clinical condition and another 24.5% of cases of returned chemotherapy regimen were attributed to adverse drug reactions.
CONCLUSION: Wastage associated to non-preventable reasons such as adverse drug reactions and preventable causes like refusal of patients can be further reduced by using newer healthcare innovations and establishment of written institutional protocols or standard operating procedures as references for in-charge healthcare personnel when cytotoxic drug-related issues occur. Adoption of cost-saving strategies that have been proven by studies could further improve current cost containment strategies.
METHODS: Cancer 10-pathway reporter array was performed to screen the pathways affected by Phyllanthus in lung carcinoma cell line (A549) to exert its antimetastatic effects. Results from this array were then confirmed with western blotting, cell cycle analysis, zymography technique, and cell based ELISA assay for human total iNOS. Two-dimensional gel electrophoresis was subsequently carried out to study the differential protein expressions in A549 after treatment with Phyllanthus.
RESULTS: Phyllanthus was observed to cause antimetastatic activities by inhibiting ERK1/2 pathway via suppression of Raf protein. Inhibition of this pathway resulted in the suppression of MMP2, MMP7, and MMP9 expression to stop A549 metastasis. Phyllanthus also inhibits hypoxia pathway via inhibition of HIF-1α that led to reduced VEGF and iNOS expressions. Proteomic analysis revealed a number of proteins downregulated by Phyllanthus that were involved in metastatic processes, including invasion and mobility proteins (cytoskeletal proteins), transcriptional proteins (proliferating cell nuclear antigen; zinc finger protein), antiapoptotic protein (Bcl2) and various glycolytic enzymes. Among the four Phyllanthus species tested, P. urinaria showed the greatest antimetastatic activity.
CONCLUSIONS: Phyllanthus inhibits A549 metastasis by suppressing ERK1/2 and hypoxia pathways that led to suppression of various critical proteins for A549 invasion and migration.
METHOD: An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection.
RESULTS: Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells.
CONCLUSION: This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.