MATERIALS AND METHODS: Silver nanoparticles (dAgNps) were synthesized by reacting phytochemicals of D. microcarpum leaves with silver nitrate for 12 hours. Cell viability assay was carried out to investigate the cytotoxic effect of dAgNps on HeLa and PANC-1 cells.

RESULTS: Scanning electron microscopy (SEM) and transmission electron microscopy(TEM) results revealed the average sizes of dAgNps are 81 nm and 84 nm respectively. The x-ray diffraction (XRD) pattern of dAgNps was similar to that of face centered cubic(fcc) structure of silver as reported by joint committee on powder diffraction standards (JCPDS) and fourier-transform infrared spectroscopy (FTIR) analysis showed that some phytochemicals of D. microcarpum such as polyphenols and flavonoids were likely involved in the reduction of Ag+ to form nanoparticles. Finally, cell viability assay revealed dAgNps inhibited PANC-1 and HeLa cell proliferations with IC50 values of 84 and 31.5 µg/ml respectively.

METHODS: A single-centre retrospective study investigating the feasibility, safety and outcomes of both linear EBUS-inserted FMs and subsequent FM-guided SBRT for UC-oligometastatic disease. Motion analyses of FMs were also performed.

RESULTS: Thirty outpatients underwent 32 EBUS-FM insertion procedures with 100 % success, and no major procedural mortality or morbidity. Minor complications were 4.8 % incidence of delayed FM-displacement. UC FM-guided SBRT was completed in 20 patients with 99.9 % fractions delivered. Median SBRT dose delivered was 40 Gy over a median of 8 fractions. Majority of adverse events were Grade 1 and there was no SBRT-related mortality. Local control with SBRT was 95 %, with overall survival at 1-year and 3-years of 90 % and 56.3 % respectively. Median overall survival after SBRT was 43.6 months. FM movements in UC areas were recorded being greatest in the superior-inferior axis.

MATERIALS AND METHOD: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed.

RESULTS: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells.

METHODS: We integrated genetic knockout (KO) of golgin-97, animal models (zebrafish and xenograft mice), multi-omics analysis (next-generation sequencing and proteomics), bioinformatics analysis, and kinase inhibitor treatment to evaluate the effects of golgin-97 KO in triple-negative breast cancer cells. Gene knockdown and kinase inhibitor treatment followed by qRT‒PCR, Western blotting, cell viability, migration, and cytotoxicity assays were performed to elucidate the mechanisms of golgin-97 KO-mediated cancer invasion. A xenograft mouse model was used to investigate cancer progression and drug therapy.

RESULTS: We demonstrated that golgin-97 KO promoted breast cell metastasis in zebrafish and xenograft mouse models. Multi-omics analysis revealed that the Wnt signaling pathway, MAPK kinase cascades, and inflammatory cytokines are involved in golgin-97 KO-induced breast cancer progression. Targeting the ERK1/2 and p38 MAPK pathways effectively attenuated golgin-97-induced cancer cell migration, reduced the expression of inflammatory mediators, and enhanced the chemotherapeutic effect of paclitaxel in vitro and in vivo. Specifically, compared with the paclitaxel regimen, the combination of ERK1/2 and p38 MAPK inhibitors significantly prevented lung metastasis and lung injury. We further demonstrated that hypoxia is a physiological condition that reduces golgin-97 expression in cancer, revealing a novel and potential feedback loop between ERK/MAPK signaling and golgin-97.

METHODS: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).

RESULTS: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09).

AIM OF STUDY: Although anticancer activity has been reported for the plant, the goal of the study was designed to isolate and characterize the active metabolites from G. mangostana and measure their cytotoxic properties. In this research, the mechanism of antiproliferative/cytotoxic effects of the tested compounds was investigated.

MATERIALS AND METHODS: The CHCl3 fraction of the air-dried fruit hulls was repeatedly chromatographed on SiO2, RP18, Diaion HP-20, and polyamide columns to furnish fourteen compounds. The structures of these metabolites were proven by UV, IR, 1D, and 2D NMR measurements and HRESIMS. Additionally, the cytotoxic potential of all compounds was assessed against MCF-7, HCT-116, and HepG2 cell lines using SRB-U assay. Antiproliferative and cell cycle interference effects of potentially potent compounds were tested using DNA content flow cytometry. The mechanism of cell death induction was also studied using annexin-V/PI differential staining coupled with flow cytometry.

RESULTS: The CHCl3 soluble fraction afforded two new xanthones: mangostanaxanthones V (1) and VI (2), along with twelve known compounds: mangostanaxanthone IV (3), β-mangostin (4), garcinone E (5), α-mangostin (6), nor-mangostin (7), garcimangosone D (8), aromadendrin-8-C-β-D-glucopyranoside (9), 1,2,4,5-tetrahydroxybenzene (10), 2,4,3`-trihydroxybenzophenone-6-O-β-glucopyranoside (11), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (12), epicatechin (13), and 2,4,6,3`,5`-pentahydroxybenzophenone (14). Only compound 5 showed considerable antiproliferative/cytotoxic effects with IC50's ranging from 15.8 to 16.7µM. Compounds 3, 4, and 6 showed moderate to weak cytotoxic effects (IC50's ranged from 45.7 to 116.4µM). Using DNA content flow cytometry, it was found that only 5 induced significant cell cycle arrest at G0/G1-phase which is indicative of its antiproliferative properties. Additionally, by using annexin V-FITC/PI differential staining, 5 induced cells killing effect via the induction of apoptosis and necrosis in both HepG2 and HCT116 cells. Compound 3 produce necrosis and apoptosis only in HCT116 cells. On contrary, 6 induced apoptosis and necrosis in HepG2 cells and moderate necrosis in HCT116 cells.

METHODS: Patients who underwent major ablative surgery of the head and neck region with neck dissection were identified and clinical records were assessed. Inclusion criteria were stage I-IV oral and oropharyngeal malignancies necessitating resection with or without radiotherapy from 2004 to 2009. All individuals had a pre-operative assessment prior to the surgery. The post operative assessment period ranged from 1 year to 5 years. Survival distributions were analyzed using Kaplan-Meier curves.

RESULTS: 87 patients (males:38%; females:62%) were included in this study, with an age range of 21-85 years. Some 78% underwent neck dissections while 63% had surgery and radiotherapy. Nodal recurrence was detected in 5.7% while 20.5% had primary site recurrence within the study period. Kaplan-Meier survival analysis revealed that the median survival time was 57 months. One year overall survival (OS) rate was 72.7% and three year overall survival rate dropped to 61.5%. On OS analysis, the log-rank test showed a significant difference of survival between Malay and Chinese patients (Bonferroni correction p=0.033). Recurrence-free survival (RFS) analysis revealed that 25% of the patients have reached the event of recurrence at 46 months. One year RFS rate was 85.2% and the three year survival rate was 76.1%. In the RFS analysis, the log-rank test showed a significant difference in the event of recurrence and nodal metastasis (p<0.001).

OBJECTIVE: To explore the feasibility of using cyclin D1 as a prognostic marker in tongue and cheek SCC by the fluorescent-in-situ hybridization (FISH) method.

METHODS: Fifty paraffin-embedded samples (25 each of cheek and tongue SCCs) were obtained from the archives of the Oral Pathology Diagnostic Laboratory. Sociodemographic data, histopathologic diagnoses, lymph node status and survival data were obtained from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS)coordinated by the Oral Cancer Research and Coordinating Centre (OCRCC), University of Malaya. The FISH technique was used to detect the amplification of cyclin D1 using the Vysis protocol. Statistical correlations of cyclin D1 with site and lymph node status were analyzed using the Fisher exact test. Kaplan-Meier and Log Rank (Mantel-Cox) test were used to analyze cyclin D1 amplification and median survival time.

RESULTS: Positive amplification of cyclin D1 was detected in 72% (36) of OSCCs. Detection of positive amplification for cyclin D1 was observed in 88% (22) and 56% (14) of the tongue and cheek tumors, respectively, where the difference was statistically significant (P=0.012). Lymph node metastasis of cheek SCCs showed a trend towards a significant association (P= 0.098) with cyclin D1 amplification whereas the lymph node metastasis of tongue SCC was clearly not significant (P=0.593).There was a statistically significant correlation between cyclin D1 positivity and survival rate (P=0.009) for overall SCC cases and (P<0.001) for cheek SCC cases.