Displaying publications 21 - 40 of 197 in total

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  1. Brandão A, Paulo P, Maia S, Pinheiro M, Peixoto A, Cardoso M, et al.
    Cancers (Basel), 2020 Nov 04;12(11).
    PMID: 33158149 DOI: 10.3390/cancers12113254
    The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
    Matched MeSH terms: Prostatic Neoplasms
  2. Ibau C, Arshad MKM, Gopinath SCB, Nuzaihan M N M, Fathil MFM, Shamsuddin SA
    Int J Biol Macromol, 2020 Nov 01;162:1924-1936.
    PMID: 32822729 DOI: 10.1016/j.ijbiomac.2020.08.125
    This work explores Electrochemical Impedance Spectroscopy (EIS) detection for a highly-sensitive quantification of prostate-specific antigen (PSA) in Faradaic (f-EIS) and non-Faradaic modes (nf-EIS). Immobilization of monoclonal antibody specific to PSA (anti-PSA) was performed using 1-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride and N-hydroxysuccinimide crosslinking agents in order to conjugate carboxylic (-COOH) terminated group of 16-Mercaptoundecanoic acid with amine (-NH3+) on anti-PSA epitope. This approach offers simple and efficient approach to form a strong, covalently bound thiol-gold (SAu) for a reliable SAM layer formation. Studies on the topographic of pristine Au-IDE surface were performed by Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy techniques, meanwhile a 3-dimensional optical surface profiler, Atomic Force Microscopy and X-ray Photoelectron Spectroscopy techniques were used to validate the successful functionalization steps on the sensor transducer surface. Detection of PSA in f-EIS mode was carried out by measuring the response in charge transfer resistance (Rct) and impedance change (Z), meanwhile in nf-EIS mode, the changes in device capacitance was monitored. In f-EIS mode, the sensor reveals a logarithmic detection of PSA in a range of 100 ng/ml down to 0.01 ng/ml in Phosphate Buffered Saline with a recorded sensitivity of 2.412 kΩ/log10 ([PSA] ng/ml) and the limit of detection (LOD) down to 0.01 ng/ml. The nf-EIS detection mode yields a logarithmic detection range of 5000 ng/ml down to 0.5 ng/ml, with a sensitivity of 8.570 nF/log10 ([PSA] ng/ml) and an LOD of 0.5 ng/ml. The developed bio-assay yields great device stability, specificity to PSA and repeatability of detection that would pave its way for the future development into portable lab-on-chip bio-sensing system.
    Matched MeSH terms: Prostatic Neoplasms/diagnosis
  3. Nalairndran G, Hassan Abdul Razack A, Mai CW, Fei-Lei Chung F, Chan KK, Hii LW, et al.
    J Cell Mol Med, 2020 Oct;24(20):12188-12198.
    PMID: 32926495 DOI: 10.1111/jcmm.15876
    Prostate cancer (PCa) is the most common malignancy and is the second leading cause of cancer among men globally. Using a kinome-wide lentiviral small-hairpin RNA (shRNA) library screen, we identified phosphoinositide-dependent kinase-1 (PDPK1) as a potential mediator of cell survival in PCa cells. We showed that knock-down of endogenous human PDPK1 induced significant tumour-specific cell death in PCa cells (DU145 and PC3) but not in the normal prostate epithelial cells (RWPE-1). Further analyses revealed that PDPK1 mediates cancer cell survival predominantly via activation of serum/glucocorticoid-regulated kinase 3 (SGK3). Knock-down of endogenous PDPK1 in DU145 and PC3 cells significantly reduced SGK3 phosphorylation while ectopic expression of a constitutively active SGK3 completely abrogated the apoptosis induced by PDPK1. In contrast, no such effect was observed in SGK1 and AKT phosphorylation following PDPK1 knock-down. Importantly, PDPK1 inhibitors (GSK2334470 and BX-795) significantly reduced tumour-specific cell growth and synergized docetaxel sensitivity in PCa cells. In summary, our results demonstrated that PDPK1 mediates PCa cells' survival through SGK3 signalling and suggest that inactivation of this PDPK1-SGK3 axis may potentially serve as a novel therapeutic intervention for future treatment of PCa.
    Matched MeSH terms: Prostatic Neoplasms/drug therapy; Prostatic Neoplasms/enzymology*; Prostatic Neoplasms/pathology*
  4. Albujja MH, Messaudi SA, Vasudevan R, Al Ghamdi S, Chong PP, Ghani KA, et al.
    Asian Pac J Cancer Prev, 2020 08 01;21(8):2271-2280.
    PMID: 32856855 DOI: 10.31557/APJCP.2020.21.8.2271
    BACKGROUND: The X-chromosome has been suggested to play a role in prostate cancer (PrCa) since epidemiological studies have provided evidence for an X-linked mode of inheritance for PrCa based on the higher relative risk among men who report an affected brother(s) as compared to those reporting an affected father. The aim of this study was to examine the potential association between the forensic STR markers located at four regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28 and the risk of BPH and PrCa to confirm the impact of ChrX in the PrCa incidence. This may be helpful in the incorporation of STRs genetic variation in the early detection of men population at risk of developing PrCa.

    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.

    Matched MeSH terms: Prostatic Neoplasms/genetics; Prostatic Neoplasms/epidemiology; Prostatic Neoplasms/pathology*
  5. Othman H, Abu Yamin AH, Md Isa N, Bahadzor B, Syed Zakaria SZ
    Malays J Pathol, 2020 Aug;42(2):209-214.
    PMID: 32860373
    INTRODUCTION: Prostate health index (PHI) has been shown to have better diagnostic accuracy in predicting prostate cancer (PCa) in men with total prostate-specific antigen (PSA) levels between 4-10ng/ml. However, little is known of its value in men with elevated PSA beyond this range. This study aimed to evaluate the diagnostic performance of PHI in Malaysian men with elevated PSA values ≤ 20ng/ml.

    MATERIALS AND METHODS: From March 2015 to August 2016, all men consecutively undergoing transrectal ultrasound (TRUS)-guided prostate biopsy with total PSA values ≤ 20ng/ ml were recruited. Blood samples were taken immediately before undergoing prostate biopsy. The performance of total PSA, %fPSA, %p2PSA and PHI in determining the presence of PCa on prostate biopsy were compared.

    RESULTS: PCa was diagnosed in 25 of 84 patients (29.7%). %p2PSA and PHI values were significantly higher (p<0.05) in patients with PCa than those without PCa. The areas under the receiver operating characteristic curves for total PSA, %fPSA, %p2PSA and PHI were 0.558, 0.560, 0.734 and 0.746, respectively. At 90% sensitivity, the specificity of PHI (42.4%) was five times better than total PSA (8.5%) and two times better than %fPSA (20.3%). By utilising PHI cut-off >22.52, 27 of 84 (32.1%) patients could have avoided undergoing biopsy.

    CONCLUSION: Findings of our study support the potential clinical effectiveness of PHI in predicting PCa in a wider concentration range of total PSA up to 20ng/ml.

    Matched MeSH terms: Prostatic Neoplasms/diagnosis*; Prostatic Neoplasms/pathology
  6. Lim LY, Tan GH, Zainuddin ZM, Fam XI, Goh EH, Syaris OS, et al.
    Urol Ann, 2020 07 17;12(3):276-282.
    PMID: 33100755 DOI: 10.4103/UA.UA_98_19
    Purpose: There is mounting evidence to suggest that multiparametric magnetic resonance imaging (mpMRI)-guided biopsy is better than systematic biopsy for the diagnosis of prostate cancer (PCa). Cognitive fusion biopsy (CFB) involves targeted biopsies of areas of suspicious lesions noted on the mpMRI by transrectal ultrasound (TRUS) operator. This study was undertaken to determine the accuracy of mpMRI of the prostate with Prostate Imaging-Reporting and Data System (PI-RADS) version 2 in detecting PCa. We also compare the cancer detection rates between systematic 12-core TRUS biopsy and CFB.

    Materials and Methods: Sixty-nine men underwent mpMRI of the prostate followed by TRUS biopsy. In addition to 12-core biopsy, CFB was performed on abnormal lesions detected on MRI.

    Results: Abnormal lesions were identified in 98.6% of the patients, and 59.4% had the highest PI-RADS score of 3 or more. With the use of PI-RADS 3 as cutoff, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI for the detection of PCa were 91.7%, 57.8%, 53.7%, and 92.8%, respectively. With the use of PI-RADS 4 as cutoff, the sensitivity, specificity, PPV, and NPV of mpMRI were 66.7%, 91.1%, 80%, and 83.7%, respectively. Systematic biopsy detected more PCa compared to CFB (29% vs. 26.1%), but CFB detected more significant (Gleason grade ≥7) PCa (17.4% vs. 14.5%) (P < 0.01). CFB cores have a higher PCa detection rate as compared to systematic cores (P < 0.01).

    Conclusions: mpMRI has a good predictive ability for PCa. CFB is superior to systematic biopsy in the detection of the significant PCa.

    Matched MeSH terms: Prostatic Neoplasms
  7. Soopramanien M, Khan NA, Ghimire A, Sagathevan K, Siddiqui R
    Biology (Basel), 2020 Jul 02;9(7).
    PMID: 32630812 DOI: 10.3390/biology9070150
    Despite intensive research, cancer incidence and mortality continue to rise. Consequently, the necessity to develop effective anti-cancer therapy is apparent. We have recently shown that the gut bacteria of animals living in polluted environments, such as crocodiles, are a potential source of novel anti-tumor molecules. To extend this work to other resilient species, we investigated the anti-tumor effects of gut bacteria of Heterometrus spinifer (a scorpion). Bacteria from the feces and gut were isolated, identified and evaluated for their anti-tumor effects. Bacterial-conditioned media was prepared in Roswell Park Memorial Institute (RPMI) 1640 media, and cytotoxicity and growth inhibitory properties were examined against cervical (HeLa) cancer cells. Liquid chromatography-mass spectrometry (LC-MS) was conducted to establish the identity of the molecules. Eighteen bacteria species from the gut (HSG01-18) and ten bacteria species from feces (HSF01-10) were tested for anti-tumor effects. Bacterial-conditioned media from scorpion gut and feces exhibited significant growth inhibitory effects against HeLa cells of 66.9% and 83.8%, respectively. Microscopic analysis of cancer cells treated with conditioned media HSG12 and HSG16 revealed apoptosis-like effects. HSG12 was identified as Pseudomonas aeruginosa and HSG16 was identified as Bacillus subtilis. Both conditioned media exhibited 100% growth inhibitory effects versus a selection of cancer cells, comprising cervical, breast and prostate cancer cells. LC-MS indicated the presence of 72 and 38 compounds, detected from HSG12 and HSG16, respectively. Out of these compounds, 47 were successfully identified while the remainder were unidentified and are possibly novel. This study suggests that the fecal and gut microbiota of scorpions might possess molecules with anti-cancer properties, however, further intensive research is needed to assess these expectations.
    Matched MeSH terms: Prostatic Neoplasms
  8. Heng MP, Sim KS, Tan KW
    J Inorg Biochem, 2020 07;208:111097.
    PMID: 32438269 DOI: 10.1016/j.jinorgbio.2020.111097
    Two new Schiff base ligands (TE and TF) were prepared from conjugation of testosterone with 4-(4-ethylphenyl)-3-thiosemicarbazide and 4-(4-fluorophenyl)-3-thiosemicarbazide, respectively. Their nickel (NE and NF) and zinc (ZE and ZF) complexes were reported. X-ray crystallography revealed a distorted square planar geometry was adopted by NE. The compounds demonstrated excellent selectivity towards the colorectal carcinoma cell line HCT 116 despite their weak preferences towards the prostate cancer cell lines (PC-3 and LNCaP). Against HCT 116, all these compounds were able to arrest cell cycle at G0/G1 phase and induce apoptosis via mitochondria-dependent (TE, NE, and TF) and extrinsic apoptotic pathway (ZE, NF, and ZF). Moreover, only ZE was able to act as topoisomease I poison and halt its enzymatic reactions although all compounds presented excellent affinity towards DNA.
    Matched MeSH terms: Prostatic Neoplasms
  9. Ting CY, Teh GC, Yu KL, Alias H, Tan HM, Wong LP
    Eur J Cancer Care (Engl), 2020 Jul;29(4):e13248.
    PMID: 32495472 DOI: 10.1111/ecc.13248
    OBJECTIVE: This study examined the prevalence of self-perceived burden (SPB) and its association with health-related quality of life (HRQoL) among urologic cancer patients.

    METHODS: This was a prospective, cross-sectional study. A total of 429 respondents diagnosed with urologic cancers (prostate, bladder and renal cancer) from Sarawak General Hospital and Subang Jaya Medical Centre in Malaysia were interviewed by using a structured questionnaire. SPB and HRQoL were measured by the Self-perceived Burden Scale and the Functional Assessment of Cancer Therapy-General 7 Item Scale respectively.

    RESULTS AND CONCLUSION: Self-perceived burden was experienced by 73.2% of the respondents. Respondents who had a lower education level, a monthly household income

    Matched MeSH terms: Prostatic Neoplasms/physiopathology; Prostatic Neoplasms/psychology*
  10. Lim J, Amantakul A, Shariff N, Lojanapiwat B, Alip A, Ong TA, et al.
    Cancer Med, 2020 Jul;9(13):4613-4621.
    PMID: 32374087 DOI: 10.1002/cam4.3101
    It is of much interest to understand the efficacy of abiraterone acetate (AA) in routine clinical practice. We assessed the clinical outcome of AA in patients with metastatic castration-resistant prostate cancer (mCRPC) and determined clinical factors associated with AA treatment duration in real-world setting. This real-world cohort consisted of 93 patients with mCRPC treated with AA in Thailand (58.1%) and Malaysia (41.9%). Primary endpoints were overall survival (OS) and biochemical progression-free survival (bPFS). Secondary endpoints were predictors associated with AA treatment duration evaluated with Cox proportional hazards regression. Around 74% were chemotherapy-naïve. The median AA treatment duration was 10 months (IQR 5.6-17.1). Malaysians had a relatively lower median OS and bPFS (OS 17.8 months; 95% CI 6.4-29.1, bPFS 10.4 months; 95% CI 8.8-12.0) compared to Thais (OS 27.0 months; 95% CI 11.3-42.7, bPFS 14.0 months; 95% CI 5.8-22.2), although it did not achieve statistical significance (P > .05). Patients with longer AA treatment duration (>10 months) had lower risk of death and longer bPFS, compared to those with shorter AA treatment duration (≤10 months) (hazard ratio [HR] 0.10, 95% CI 0.05-0.22 and HR 0.13, 95% CI 0.06-0.25, respectively). Multivariable analysis showed that PSA at AA initiation, presence of PSA response and chemotherapy-naive were independently associated with AA duration (P 
    Matched MeSH terms: Prostatic Neoplasms, Castration-Resistant/blood; Prostatic Neoplasms, Castration-Resistant/drug therapy*; Prostatic Neoplasms, Castration-Resistant/mortality; Prostatic Neoplasms, Castration-Resistant/pathology
  11. Jayaraj R, Raymond G, Krishnan S, Tzou KS, Baxi S, Ram MR, et al.
    Cancers (Basel), 2020 May 09;12(5).
    PMID: 32397507 DOI: 10.3390/cancers12051199
    Background: Prostate cancer (PrC) is the second-most frequent cancer in men, its incidence is emerging globally and is the fifth leading cause of death worldwide. While diagnosis and prognosis of PrC have been studied well, the associated therapeutic biomarkers have not yet been investigated comprehensively. This systematic review and meta-analysis aim to evaluate the theragnostic effects of microRNA expressions on chemoresistance in prostate cancer and to analyse the utility of miRNAs as clinical theragnostic biomarkers. Methods: A systematic literature search for studies reporting miRNA expressions and their role in chemoresistance in PrC published until 2018 was collected from bibliographic databases. The evaluation of data was performed as per PRISMA guidelines for systematic review and meta-analysis. Meta-analysis was performed using a random-effects model using Comprehensive Meta-Analysis (CMA) software. Heterogeneity between studies was analysed using Cochran's Q test, I2 and the Tau statistic. Quality assessment of the studies was performed using the Newcastle-Ottawa Scale (NOS) for the methodological assessment of cohort studies. Publication bias was assessed using Egger's bias indicator test, Orwin and classic fail-safe N test, Begg and Mazumdar rank collection test, and Duval and Tweedie's trim and fill methods. Findings: Out of 2909 studies retrieved, 79 studies were shortlisted and reviewed. A total of 17 studies met our eligibility criteria, from which 779 PrC patients and 17 chemotherapy drugs were examined, including docetaxel and paclitaxel. The majority of the drug regulatory genes reported were involved in cell survival, angiogenesis and cell proliferation pathways. We studied 42 miRNAs across all studies, out of which two miRNAs were found to be influencing chemosensitivity, while 21 were involved in chemoresistance. However, the remaining 19 miRNAs did not appear to have any theragnostic effects. Besides, the prognostic impact of the miRNAs was evaluated and had a pooled HR value of 1.960 with 95% CI (1.377-2.791). Interpretation: The observation of the current study depicts the significance of miRNA expression as a theragnostic biomarker in medical oncology. This review suggests the involvement of specific miRNAs as predictors of chemoresistance and sensitivity in PrC. Hence, the current systematic review and meta-analysis provide insight on the use of miRNA as PrC biomarkers, which can be harnessed as molecular candidates for therapeutic targeting.
    Matched MeSH terms: Prostatic Neoplasms
  12. Ting CY, Teh GC, Yu KL, Alias H, Tan HM, Wong LP
    Support Care Cancer, 2020 Apr;28(4):1703-1715.
    PMID: 31292755 DOI: 10.1007/s00520-019-04975-y
    PURPOSE: This study examined the prevalence of financial toxicity (FT) and associated factors among urologic cancer patients. The association between FT and health-related quality of life (HRQoL) was also investigated.

    METHODS: A total of 429 respondents diagnosed with urologic cancers (prostate cancer, bladder and renal cancer) from Sarawak General Hospital and Subang Jaya Medical Centre in Malaysia were interviewed using a structured questionnaire. Objective and subjective FT were measured by catastrophic health expenditure (healthcare-cost-to-income ratio greater than 40%) and the Personal Financial Well-being Scale, respectively. HRQoL was measured with the Functional Assessment of Cancer Therapy - General 7 Items scale.

    RESULTS: Objective and subjective FT were experienced by 16.1 and 47.3% of the respondents, respectively. Respondents who sought treatment at a private hospital and had out-of-pocket health expenditures were more likely to experience objective FT, after adjustment for covariates. Respondents who were female and had a monthly household income less than MYR 5000 were more likely to experience average to high subjective FT. Greater objective FT (OR = 2.75, 95% CI 1.09-6.95) and subjective FT (OR = 4.68, 95% CI 2.63-8.30) were associated with poor HRQoL.

    CONCLUSIONS: The significant association between both objective and subjective FT and HRQoL highlights the importance of reducing FT among urologic cancer patients. Subjective FT was found to have a greater negative impact on HRQoL.

    Matched MeSH terms: Prostatic Neoplasms/drug therapy; Prostatic Neoplasms/economics*
  13. Uemura H, Ye D, Kanesvaran R, Chiong E, Lojanapiwat B, Pu YS, et al.
    BJU Int, 2020 04;125(4):541-552.
    PMID: 31868997 DOI: 10.1111/bju.14980
    OBJECTIVES: To document the management of advanced prostate cancer including diagnosis, prognosis, treatment, and care, in real-world practice in Asia using the United in Fight against prOstate cancer (UFO) registry.

    PATIENTS AND METHODS: We established a multi-national, longitudinal, observational registry of patients with prostate cancer presenting to participating tertiary care hospitals in eight Asian countries. A total of 3636 eligible patients with existing or newly diagnosed high-risk localised prostate cancer (HRL), non-metastatic biochemically recurrent prostate cancer (M0), or metastatic prostate cancer (M1), were consecutively enrolled and are being followed-up for 5 years. Patient history, demographic and disease characteristics, treatment and treatment decisions, were collected at first prostate cancer diagnosis and at enrolment. Patient-reported quality of life was prospectively assessed using the European Quality of Life-five Dimensions, five Levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy for Prostate Cancer questionnaires. In the present study, we report the first interim analysis of 2063 patients enrolled from study start (15 September 2015) until 18 May 2017.

    RESULTS: Of the 2063 enrolled patients, 357 (17%), 378 (19%), and 1328 (64%) had HRL, M0 or M1 prostate cancer, respectively. The mean age at first diagnosis was similar in each group, 56% of all patients had extracapsular extension of their tumour, 28% had regional lymph node metastasis, and 53% had distant metastases. At enrolment, 62% of patients had at least one co-morbidity (mainly cardiovascular disease or diabetes), 91.8% of M1 patients had an Eastern Cooperative Oncology Group performance score of <2 and the mean EQ-5D-5L visual analogue score was 74.6-79.6 across cohorts. Treatment of M1 patients was primarily with combined androgen blockade (58%) or androgen-deprivation therapy (either orchidectomy or luteinising hormone-releasing hormone analogues) (32%). Decisions to start therapy were mainly driven by treatment guidelines and disease progression. Decision to discontinue therapy was most often due to disease progression (hormonal drug therapy) or completion of therapy (chemotherapy).

    CONCLUSION: In the UFO registry of advanced prostate cancer in Asia, regional differences exist in prostate cancer treatment patterns that will be explored more deeply during the follow-up period; prospective follow-up is ongoing. The UFO registry will provide valuable descriptive data on current disease characteristics and treatment landscape amongst patients with prostate cancer in Asia.

    Matched MeSH terms: Prostatic Neoplasms/diagnosis*; Prostatic Neoplasms/therapy*
  14. Abd Wahab NA, Lajis NH, Abas F, Othman I, Naidu R
    Nutrients, 2020 Mar 02;12(3).
    PMID: 32131560 DOI: 10.3390/nu12030679
    Prostate cancer (PCa) is a heterogeneous disease and ranked as the second leading cause of cancer-related deaths in males worldwide. The global burden of PCa keeps rising regardless of the emerging cutting-edge technologies for treatment and drug designation. There are a number of treatment options which are effectively treating localised and androgen-dependent PCa (ADPC) through hormonal and surgery treatments. However, over time, these cancerous cells progress to androgen-independent PCa (AIPC) which continuously grow despite hormone depletion. At this particular stage, androgen depletion therapy (ADT) is no longer effective as these cancerous cells are rendered hormone-insensitive and capable of growing in the absence of androgen. AIPC is a lethal type of disease which leads to poor prognosis and is a major contributor to PCa death rates. A natural product-derived compound, curcumin has been identified as a pleiotropic compound which capable of influencing and modulating a diverse range of molecular targets and signalling pathways in order to exhibit its medicinal properties. Due to such multi-targeted behaviour, its benefits are paramount in combating a wide range of diseases including inflammation and cancer disease. Curcumin exhibits anti-cancer properties by suppressing cancer cells growth and survival, inflammation, invasion, cell proliferation as well as possesses the ability to induce apoptosis in malignant cells. In this review, we investigate the mechanism of curcumin by modulating multiple signalling pathways such as androgen receptor (AR) signalling, activating protein-1 (AP-1), phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), wingless (Wnt)/ß-catenin signalling, and molecular targets including nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and cyclin D1 which are implicated in the development and progression of both types of PCa, ADPC and AIPC. In addition, the role of microRNAs and clinical trials on the anti-cancer effects of curcumin in PCa patients were also reviewed.
    Matched MeSH terms: Prostatic Neoplasms/drug therapy*; Prostatic Neoplasms/metabolism; Prostatic Neoplasms/mortality; Prostatic Neoplasms/pathology
  15. Loveridge CJ, Slater S, Campbell KJ, Nam NA, Knight J, Ahmad I, et al.
    Oncogene, 2020 02;39(8):1797-1806.
    PMID: 31740786 DOI: 10.1038/s41388-019-1106-x
    BRF1 is a rate-limiting factor for RNA Polymerase III-mediated transcription and is elevated in numerous cancers. Here, we report that elevated levels of BRF1 associate with poor prognosis in human prostate cancer. In vitro studies in human prostate cancer cell lines demonstrated that transient overexpression of BRF1 increased cell proliferation whereas the transient downregulation of BRF1 reduced proliferation and mediated cell cycle arrest. Consistent with our clinical observations, BRF1 overexpression in a Pten-deficient mouse (PtenΔ/Δ BRF1Tg) prostate cancer model accelerated prostate carcinogenesis and shortened survival. In PtenΔ/Δ BRF1Tg tumours, immune and inflammatory processes were altered, with reduced tumoral infiltration of neutrophils and CD4 positive T cells, which can be explained by decreased levels of complement factor D (CFD) and C7 components of the complement cascade, an innate immune pathway that influences the adaptive immune response. We tested if the secretome was involved in BRF1-driven tumorigenesis. Unbiased proteomic analysis on BRF1-overexpresing PC3 cells confirmed reduced levels of CFD in the secretome, implicating the complement system in prostate carcinogenesis. We further identify that expression of C7 significantly correlates with expression of CD4 and has the potential to alter clinical outcome in human prostate cancer, where low levels of C7 associate with poorer prognosis.
    Matched MeSH terms: Prostatic Neoplasms/diagnosis; Prostatic Neoplasms/immunology*; Prostatic Neoplasms/metabolism; Prostatic Neoplasms/pathology*
  16. Patel VL, Busch EL, Friebel TM, Cronin A, Leslie G, McGuffog L, et al.
    Cancer Res, 2020 Feb 01;80(3):624-638.
    PMID: 31723001 DOI: 10.1158/0008-5472.CAN-19-1840
    Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
    Matched MeSH terms: Prostatic Neoplasms/genetics*; Prostatic Neoplasms/pathology*
  17. Schmidt JA, Fensom GK, Rinaldi S, Scalbert A, Appleby PN, Achaintre D, et al.
    Int J Cancer, 2020 Feb 01;146(3):720-730.
    PMID: 30951192 DOI: 10.1002/ijc.32314
    Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD ) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD  = 0.77, 95% confidence interval 0.66-0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD  = 0.72, 0.57-0.90), or lysophosphatidylcholines (OR1SD  = 0.81, 0.69-0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD  = 0.77, 0.61-0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.
    Matched MeSH terms: Prostatic Neoplasms/blood; Prostatic Neoplasms/metabolism; Prostatic Neoplasms/pathology*
  18. Sapili H, Ho CS, Malagobadan S, Arshad NM, Nagoor NH
    Sci Rep, 2020 01 22;10(1):986.
    PMID: 31969640 DOI: 10.1038/s41598-020-57781-6
    Geranylated 4-phenylcoumarins DMDP-1 and DMDP-2 isolated from Mesua elegans were elucidated for their role in inducing caspase-independent programmed cell death (CI-PCD) in prostate cancer cell lines, PC-3 and DU 145, respectively. Cell homeostasis disruption was demonstrated upon treatment, as shown by the increase in calcium ion through colourimetric assay and endoplasmic reticulum (ER) stress markers GRP 78 and p-eIF2α through western blot. Subsequently, cytoplasmic death protease calpain-2 also showed increased activity during DMDP-1 & -2 treatments, while lysosomic death protease cathepsin B activity was significantly increased in PC-3 treated with DMDP-1. Flow cytometry showed a reduction in mitochondrial membrane potential in both cell lines, while western blotting showed translocation of mitochondrial death protease AIF into the cytoplasm in its truncated form. Furthermore, DMDP-1 & -2 treatments caused significant increase in superoxide level and oxidative DNA damage. Concurrent inhibition of calpain-2 and cathepsin B during the treatment showed an attenuation of cell death in both cell lines. Hence, DMDP-1 & -2 induce CI-PCD in prostate cancer cell lines through calpain-2 and cathepsin B.
    Matched MeSH terms: Prostatic Neoplasms/metabolism; Prostatic Neoplasms/pathology
  19. Yii RSL, Lim J, Sothilingam S, Yeoh WS, Fadzli AN, Ong TA, et al.
    Asian J Surg, 2020 Jan;43(1):87-94.
    PMID: 30962017 DOI: 10.1016/j.asjsur.2019.02.014
    OBJECTIVES: To identify the associated factors determining prostate cancer detection using transrectal ultrasound (TRUS)-guided prostate biopsy, within a multi-ethnic Malaysian population with prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml.

    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 

    Matched MeSH terms: Prostatic Neoplasms/diagnosis*; Prostatic Neoplasms/pathology
  20. Guo W, Wu X, Li Y, Gao J, Wang F, Jin Y, et al.
    J Drug Target, 2020 01;28(1):41-45.
    PMID: 30943812 DOI: 10.1080/1061186X.2019.1601199
    Purpose: The present study evaluated biochemical as well as biophysical mechanisms behind the synergistic effects of curcumin and resveratrol during prostate carcinogenesis.Methods: The rats were segregated into five groups that included normal control, 3,2'-dimethyl-4-aminobiphenyl (DMAB)treated, DMAB + curcumin treated, DMAB + resveratrol-treated and DMAB + curcumin + resveratrol-treated.Results: The DMAB treatment resulted in a significant increase in the levels of lipid peroxidation (LPO) in DMAB treated rats. Also, significant changes were recorded in the enzyme activities of both drug metabolising enzyme and antioxidant enzymes after DMAB treatment. Further, radiorespirometric studies showed a significant increase in the 14C-glucose turnover as well as 14C-glucose uptake in the prostate slices of DMAB treated rats. Moreover, a significant rise in cell proliferation was confirmed indirectly by enhanced uptake of 3H-thymidine in the prostate slices of DMAB treated rats. Interestingly, combined treatment of curcumin and resveratrol to DMAB treated animals resulted in a significant decrease in lipid peroxidation, 14C glucose uptakes/turnover and 3H-thymidine uptake in the DMAB treated rats. Besides this, curcumin and resveratrol in combination significantly modulated biochemical indices including drug-metabolising enzymes; antioxidant enzymes in DMBA treated rats.Conclusion: The study, therefore, concludes that the combination of curcumin and resveratrol holds strong modulatory potential against prostate carcinogenesis.
    Matched MeSH terms: Prostatic Neoplasms/drug therapy*
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