METHODS: In the present study, a prenylated flavone (isoglabratephrin) was isolated from aerial parts of Tephrosia apollinea using a bioassay-guided technique. Chemical structure of the isolated compound was elucidated using spectroscopic techniques (NMR, IR, and LC-MC), elemental analysis and confirmed by using single crystal X-ray analysis. The antiproliferative effect of isoglabratephrin was tested using three human cancer cell lines (prostate (PC3), pancreatic (PANC-1), and colon (HCT-116) and one normal cell line (human fibroblast).
RESULTS: Isoglabratephrin displayed selective inhibitory activity against proliferation of PC3 and PANC-1 cells with median inhibitory concentration values of 20.4 and 26.6 μg/ml, respectively. Isoglabratephrin demonstrated proapoptotic features, as it induced chromatin dissolution, nuclear condensation, and fragmentation. It also disrupted the mitochondrial membrane potential in the treated cancer cells.
CONCLUSION: Isoglabratephrin could be a new lead to treat human prostate (PC3) and pancreatic (PANC-1) malignancies.
METHODOLOGY: We categorise tissue images based on the texture of individual tissue components via the construction of a single classifier and also construct an ensemble learning model by merging the values obtained by each classifier. Another issue that arises is overfitting due to the high-dimensional texture of individual tissue components. We propose a new FS method, SVM-RFE(AC), that integrates a Support Vector Machine-Recursive Feature Elimination (SVM-RFE) embedded procedure with an absolute cosine (AC) filter method to prevent redundancy in the selected features of the SV-RFE and an unoptimised classifier in the AC.
RESULTS: We conducted experiments on H&E histopathological prostate and colon cancer images with respect to three prostate classifications, namely benign vs. grade 3, benign vs. grade 4 and grade 3 vs. grade 4. The colon benchmark dataset requires a distinction between grades 1 and 2, which are the most difficult cases to distinguish in the colon domain. The results obtained by both the single and ensemble classification models (which uses the product rule as its merging method) confirm that the proposed SVM-RFE(AC) is superior to the other SVM and SVM-RFE-based methods.
CONCLUSION: We developed an FS method based on SVM-RFE and AC and successfully showed that its use enabled the identification of the most crucial texture feature of each tissue component. Thus, it makes possible the distinction between multiple Gleason grades (e.g. grade 3 vs. grade 4) and its performance is far superior to other reported FS methods.
MATERIALS AND METHODS: This retrospective cross sectional study looked at prostate cancer patients seen in the Urology Departments in 2 tertiary centres over the 11 year period starting from January 2000 to May 2011. Patient demographic data, levels of PSA at diagnosis, Gleason score for the biopsy core, T-staging as well as the lymph node status were recorded and analysed.
RESULTS: 258 men were included. The mean age of those 90 men (34.9%) with bone metastasis was 69.2 ± 7.3 years. Logistic regression found that PSA level (P=0.000) at diagnosis and patient's nodal-stage (P=0.02) were the only two independent variables able to predict the probability of bone metastasis among the newly diagnosed prostate cancer patients. Among those with a low PSA level less than 20 ng/ml, and less than 10 ng/ml, bone metastasis were detected in 10.3% (12 out of 117) and 9.7% (7 out of 72), respectively. However, by combining PSA level of 10 ng/ml or lower, and nodal negative as the two criteria to predict negative bone scan, a relatively high negative predictive value of 93.8% was obtained. The probability of bone metastasis in prostate cancer can be calculated with this formula: -1.069+0.007(PSA value, ng/ml) +1.021(Nodal status, 0 or 1)=x Probability of bone metastasis=2.718 x/1+2.718 x.
CONCLUSION: Newly diagnosed prostate cancer patients with a PSA level of 10 ng/ml or lower and negative nodes have a very low risk of bone metastasis (negative predictive value 93.8%) and therefore bone scans may not be necessary.
METHODS: Patients confirmed by transrectal-ultrasonographic-guided-biopsy performed from 2002 to 2008 were enrolled and analysed according to ethnicity, age, PSA level, Gleason score, stage of disease and survival.
RESULTS: Among 83 patients, there were 38 Malay, 40 Chinese, 3 Indians and 2 others. Median age at diagnosis was 69.9 (range: 59-93), 43 patients (51.8%) being diagnosed before the age of 70. The median PSA level upon diagnosis was 574 ng/ml (range: 1-8632) and the median Gleason score was 7 (range: 2-10). Over half were already in Stage 4 when diagnosed. The most common site of metastasis was the bone. As a result the commonest prescribed treatment was hormonal manipulation. Five patients underwent radical prostatectomy and a further thirteen patients had radical radiotherapy (stage I: 1 patient, stage II: 7 patients and stage III: 5 patients). Ten patients defaulted follow-up. The median disease-specific survival was 21.9 months (range: 1-53).
CONCLUSIONS: Prostatic carcinoma is a disease of the elderly and it is frequently diagnosed late in Malaysia. Greater efforts should be made to educate Malaysians regarding prostate cancer.
METHODS: DNA samples from 92 patients and 156 healthy controls collected from two medical centers in Riyadh, Saudi Arabia were analyzed for four regions located at X-chromosome using the Investigator® Argus X-12 QS Kit.
RESULTS: The results demonstrated that microvariant alleles of (DXS7132, DXS10146, HPRTB, DXS10134, and DXS10135) are overrepresented in the BPH group (p < 0.00001). Allele 28 of DXS10135 and allele 15 of DXS7423 could have a protective effect, OR 0.229 (95%CI, 0.066-0.79); and OR 0.439 (95%CI, 0.208-0.925). On the other hand, patients carrying allele 23 of DXS10079 and allele 26 of DXS10148 presented an increased risk to PrCa OR 4.714 (95%CI, 3.604-6.166).
CONCLUSION: The results are in concordance with the involvement of the X chromosome in PrCa and BPH development. STR allele studies may add further information from the definition of a genetic profile of PrCa resistance or susceptibility. As TBL1, AR, LDOC1, and RPL10 genes are located at regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28, respectively, these genes could play an essential role in PrCa or BPH.
MATERIALS AND METHODS: MicroRNA software predicted that miR21 targets VCL while miR29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalinfixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels.
RESULTS: QPCR confirmed that VCL messenger RNA (mRNA) was significantly down regulated while CX3CL1 was upregulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly up regulated while CX3CL1 mRNA was significantly downregulated compared to the RWPE1 case.
CONCLUSIONS: The downregulation of VCL in FFPE specimens is most likely regulated by miR21 based on the in vitro evidence but the exact mechanism of how miR21 can regulate VCL is unclear. Upregulated in CaP, CX3CL1 was found not regulated by miR29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNAmRNA interactions may provide additional knowledge for individualized study of cancers.
METHODS: Study subjects included men with initial PSA between 4.0 and 10.0 ng/ml that have undergone 12-core TRUS-guided prostate biopsy between 2009 and 2016. The prostate cancer detection rate was calculated, while potential factors associated with detection were investigated via univariable and multivariable analysis.
RESULTS: A total of 617 men from a multi-ethnic background encompassing Chinese (63.5%), Malay (23.1%) and Indian (13.3%) were studied. The overall cancer detection rate was 14.3% (88/617), which included cancers detected at biopsy 1 (first biopsy), biopsy 2 (second biopsy with previous negative biopsy) and biopsy ≥ 3 (third or more biopsies with prior negative biopsies). Indian men displayed higher detection rate (23.2%) and increased risk of prostate cancer development (OR 1.85, 95% CI 1.03-3.32, p
FINDINGS: Differences in genetics, environment, lifestyle, diet and culture are all likely to influence the management of advanced prostate cancer in the APAC region when compared with the rest of the world. When considering the strong APCCC 2017 recommendation for the use of upfront docetaxel in metastatic castration-naïve prostate cancer, the panel noted possible increased toxicity in Asian men receiving docetaxel, which would affect this recommendation in the APAC region. Although androgen receptor-targeting agents appear to be well tolerated in Asian men with metastatic castration-resistant prostate cancer, access to these drugs is very limited for financial reasons across the region. The meeting highlighted that cost and access to contemporary treatments and technologies are key factors influencing therapeutic decision-making in the APAC region. Whilst lower cost/older treatments and technologies may be an option, issues of culture and patient or physician preference mean, these may not always be acceptable. Although generic products can reduce cost in some countries, costs may still be prohibitive for lower-income patients or communities. The panellists noted the opportunity for a coordinated approach across the APAC region to address issues of access and cost. Developments in technologies and treatments are presenting new opportunities for the diagnosis and treatment of advanced prostate cancer. Differences in genetics and epidemiology affect the side-effect profiles of some drugs and influence prescribing.
CONCLUSIONS: As the field continues to evolve, collaboration across the APAC region will be important to facilitate relevant research and collection and appraisal of data relevant to APAC populations. In the meantime, the APAC APCCC 2018 meeting highlighted the critical importance of a multidisciplinary team-based approach to treatment planning and care, delivery of best-practice care by clinicians with appropriate expertise, and the importance of patient information and support for informed patient choice.
METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV.
RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers.
CONCLUSIONS: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.
METHODS: Immunoblotting, immunofluorescence, quantitative real-time PCR and flow cytometry assays investigated the expression of E-cadherin and CXCR3 isoforms. Intrasplenic inoculation of human prostate cancer (PCa) cells with spontaneous metastasis to the liver analyzed E-cadherin and CXCR3-B expression during cancer progression in vivo.
RESULTS: We found reciprocal regulation of E-cadherin and CXCR3 isoforms. E-cadherin surface expression promoted CXCR3-B presentation on the cell membrane, and to a lesser extent increased its mRNA and total protein levels. In turn, forced expression of CXCR3-A reduced E-cadherin expression level, whereas CXCR3-B increased E-cadherin in PCa. Meanwhile, a positive correlation of E-cadherin and CXCR3-B expression was found both in experimental PCa liver micro-metastases and patients' tissue.
CONCLUSIONS: CXCR3-B and E-cadherin positively correlated in vitro and in vivo in PCa cells and liver metastases, whereas CXCR3-A negatively regulated E-cadherin expression. These results suggest that CXCR3 isoforms may play important roles in cancer progression and dissemination via diametrically regulating tumor's phenotype.
Materials and methods: The antiproliferative activity of koenimbin was examined using MTT, and the apoptotic detection was carried out by acridine orange/propidium iodide (AO/PI) double-staining and multiparametric high-content screening (HCS) assays. Caspase bioluminescence assay, reverse transcription polymerase chain reaction (RT-PCR), and immunoblotting were conducted to confirm the expression of apoptotic-associated proteins. Cell cycle analysis was investigated using flow cytometry. Involvement of nuclear factor-kappa B (NF-κB) was analyzed using HCS assay. Aldefluor™ and prostasphere formation examinations were used to evaluate the impact of koenimbin on PC-3 CSCs in vitro.
Results: Koenimbin remarkably inhibited cell proliferation in a dose-dependent manner. Koenimbin induced nuclear condensation, formation of apoptotic bodies, and G0/G1 phase arrest of PC-3 cells. Koenimbin triggered the activation of caspase-3/7 and caspase-9 and the release of cytochrome c, decreased anti-apoptotic Bcl-2 and HSP70 proteins, increased pro-apoptotic Bax proteins, and inhibited NF-κB translocation from the cytoplasm to the nucleus, leading to the activation of the intrinsic apoptotic pathway. Koenimbin significantly (P<0.05) reduced the aldehyde dehydrogenase-positive cell population of PC-3 CSCs and the size and number of PC-3 CSCs in primary, secondary, and tertiary prostaspheres in vitro.
Conclusion: Koenimbin has chemotherapeutic potential that may be employed for future treatment through decreasing the recurrence of cancer, resulting in the improvement of cancer management strategies and patient survival.