Displaying publications 1 - 20 of 196 in total

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  1. Cheah WL, Ling NC, Chang KH
    Chin Clin Oncol, 2016 Feb;5(1):7.
    PMID: 26932431 DOI: 10.3978/j.issn.2304-3865.2016.02.01
    This cross-sectional study aimed to determine the prevalence of unmet supportive care needs among prostate cancer patients.
    Matched MeSH terms: Prostatic Neoplasms*
  2. Pu YS, Chiang HS, Lin CC, Huang CY, Huang KH, Chen J
    Aging Male, 2004 Jun;7(2):120-32.
    PMID: 15672937
    Although Asian people have the lowest incidence and mortality rates of prostate cancer in the world, these rates have risen rapidly in the past two decades in most Asian countries. Prostate cancer has become one of the leading male cancers in some Asian countries. In 2000, the age-adjusted incidence was over 10 per 100000 men in Japan, Taiwan, Singapore, Malaysia, the Philippines and Israel. Although some of the increases may result from enhanced detection, much of the increased incidence may be associated with westernization of the lifestyle, with increasing obesity and increased consumption of fat. The differences in incidences between native Americans and Asian immigrants are getting smaller, reflecting a possible improvement of diagnostic efforts and changes of environmental risk factors in Asian immigrants. Nevertheless, the huge variations in incidences among ethnic groups imply that there are important genetic risk factors. The stage distributions of prostate cancer in Asian populations are still unfavorable compared to those of Western developed countries. However, a trend towards diagnosing cancer with more favorable prognosis is seen in most Asian countries. Both genetic and environmental risk factors responsible for elevated risks in Asian people are being identified, which may help to reduce prostate cancer incidence in a chemopreventive setting.
    Matched MeSH terms: Prostatic Neoplasms/diagnosis; Prostatic Neoplasms/etiology; Prostatic Neoplasms/epidemiology*
  3. Raee P, Tan SC, Najafi S, Zandsalimi F, Low TY, Aghamiri S, et al.
    Reprod Biol Endocrinol, 2023 Sep 26;21(1):88.
    PMID: 37749573 DOI: 10.1186/s12958-023-01134-1
    Autophagy is a highly conserved, lysosome-dependent biological mechanism involved in the degradation and recycling of cellular components. There is growing evidence that autophagy is related to male reproductive biology, particularly spermatogenic and endocrinologic processes closely associated with male sexual and reproductive health. In recent decades, problems such as decreasing sperm count, erectile dysfunction, and infertility have worsened. In addition, reproductive health is closely related to overall health and comorbidity in aging men. In this review, we will outline the role of autophagy as a new player in aging male reproductive dysfunction and prostate cancer. We first provide an overview of the mechanisms of autophagy and its role in regulating male reproductive cells. We then focus on the link between autophagy and aging-related diseases. This is followed by a discussion of therapeutic strategies targeting autophagy before we end with limitations of current studies and suggestions for future developments in the field.
    Matched MeSH terms: Prostatic Neoplasms*
  4. Fahmy O, Khairul-Asri MG, Hadi SHSM, Gakis G, Stenzl A
    Urol Int, 2017;99(3):249-256.
    PMID: 28675891 DOI: 10.1159/000478789
    BACKGROUND: The role of radical prostatectomy (RP) is still controversial for locally advanced prostate cancer (PC). Radiotherapy (RT) and hormonal therapy (HT) are usually used as a primary treatment.

    MATERIAL AND METHODS: A systematic online search was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Eligible publications reporting the overall survival (OS) and/or disease-specific survival (DSS) were included. A total of 14 studies, including 17,869 patients, were considered for analysis. The impact of therapeutic modalities on survival was assessed, with a risk of bias assessment according to the Newcastle Ottawa Scale.

    RESULTS: For RP, RT, and HT, the mean 10-year OS was 70.7% (95% CI 61.3-80.2), 65.8% (95% CI 48.1-83.3), and 22.6% (95% CI 4.9-40.3; p = 0.001), respectively. The corresponding 10-year DSS was 84.1% (95% CI 75.1-93.2), 89.4% (95% CI 70.1-108.6), and 50.4% (95% CI 31.2-69.6; p = 0.0127), respectively. Among all treatment combinations, RP displayed significant improvement in OS when included in the treatment (Z = 4.01; p < 0.001). Adjuvant RT significantly improved DSS (Z = 2.7; p = 0.007). Combination of RT and HT favored better OS in comparison to monotherapy with RT or HT (Z = 3.61; p < 0.001).

    CONCLUSION: Improved outcomes in advanced PC were detected for RP plus adjuvant RT vs. RP alone and RT plus adjuvant HT vs. RT alone with comparable survival results between both regimens. RP with adjuvant RT may present the modality of choice when HT is contraindicated.

    Matched MeSH terms: Prostatic Neoplasms/mortality; Prostatic Neoplasms/pathology; Prostatic Neoplasms/radiotherapy*; Prostatic Neoplasms/surgery*
  5. Travis RC, Appleby PN, Martin RM, Holly JMP, Albanes D, Black A, et al.
    Cancer Res, 2016 04 15;76(8):2288-2300.
    PMID: 26921328 DOI: 10.1158/0008-5472.CAN-15-1551
    The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.
    Matched MeSH terms: Prostatic Neoplasms/blood; Prostatic Neoplasms/epidemiology*
  6. Mori A, Hashimoto K, Koroki Y, Wu DB, Masumori N
    Curr Med Res Opin, 2019 10;35(10):1745-1750.
    PMID: 31084438 DOI: 10.1080/03007995.2019.1619543
    Background and purpose: Several recent randomized controlled trials (RCTs) in non-metastatic castration resistant prostate cancer (nmCRPC) have demonstrated a significant improvement in metastasis-free survival (MFS); however, an improvement in overall survival (OS) is not reported yet. Since the surrogacy of MFS to OS has not been formally investigated in nmCRPC in Japan, this study evaluated the correlation between MFS and OS among a nmCRPC population in Japan. Methods: This is a retrospective longitudinal observational cohort study in patients with nmCRPC using the Japanese Medical Data Vision (MDV) database covering over 20 million patients. A total of 1236 patients with CRPC who had no prior medical history of cancer except prostate cancer and no distant metastasis, and who fulfilled PCWG2 criteria, were identified. Following the identification of nmCRPC, patients' medical records were investigated for subsequent events of metastasis and death. Results: The median follow-up time was 24 months. Median MFS was 28 months (95% CI: 24.0 to 33.0 months) and median OS could not be estimated (95% CI: not estimated). There was a statistically significant correlation between MFS and OS (Pearson's correlation coefficient = 0.62; 95% CI: 0.58-0.65; p 
    Matched MeSH terms: Prostatic Neoplasms, Castration-Resistant/mortality*; Prostatic Neoplasms, Castration-Resistant/pathology
  7. Kanesvaran R, Castro E, Wong A, Fizazi K, Chua MLK, Zhu Y, et al.
    ESMO Open, 2022 Aug;7(4):100518.
    PMID: 35797737 DOI: 10.1016/j.esmoop.2022.100518
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.
    Matched MeSH terms: Prostatic Neoplasms/diagnosis*; Prostatic Neoplasms/therapy*
  8. Szulkin R, Karlsson R, Whitington T, Aly M, Gronberg H, Eeles RA, et al.
    Cancer Epidemiol Biomarkers Prev, 2015 Nov;24(11):1796-800.
    PMID: 26307654 DOI: 10.1158/1055-9965.EPI-15-0543
    BACKGROUND: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical.

    METHODS: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR).

    RESULTS: We observed no significant association between genetic variants and prostate cancer survival.

    CONCLUSIONS: Common genetic variants with large impact on prostate cancer survival were not observed in this study.

    IMPACT: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes.

    Matched MeSH terms: Prostatic Neoplasms/genetics; Prostatic Neoplasms/mortality*
  9. Sahabudin RM, Arni T, Ashani N, Arumuga K, Rajenthran S, Murali S, et al.
    World J Urol, 2006 Jun;24(2):161-4.
    PMID: 16607550
    Robotic surgery was started in the Department of Urology, Hospital Kuala Lumpur, in April 2004. We present our experience in developing the program and report the results of our first 50 cases of robotic radical prostatectomy. A three-arm da Vinci robotic system was installed in our hospital in March 2004. Prior to installation, the surgeons underwent training at various centers in the United States and Paris. The operating theatre was renovated to house the system. Subsequently, the initial few cases were done with the help of proctors. Data were prospectively collected on all patients who underwent robot-assisted radical prostatectomy for localized carcinoma of the prostate. Fifty patients underwent robot assisted radical prostatectomy from March 2004 to June 2005. Their ages ranged from 52 to 75 years, (average age 60.2 years). PSA levels ranged from 2.5 to 35 ng/ml (mean 10.6 ng/ml). Prostate volume ranged from 18 to 130 cc (average 32.4 cc). Average operating time for the first 20 cases was 4 h and for the next 30 cases was 2.5 h. Patients were discharged 1-3 days post-operatively. Catheters were removed on the fifth day following a cystogram. The positive margin rate as defined by the presence of cancer cells at the inked margin was 30%. Twenty-one patients had T1c disease and one had T1b on clinical staging. Of these, two were apical margin positive. Twenty-six patients had T2 disease and eight of them were apical margin positive. Two patients had T3 disease, one of whom was apical margin positive. Five patients (10%) had PSA recurrence. Five patients had a poorly differentiated carcinoma and the rest had Gleason 6 or 7. Eighty percent of the patients were continent on follow-up at 3 months. Of those who were potent before the surgery, 50% were potent at 3-6 months. The robotic surgery program was successfully implemented at our center on the lines of a structured program, developed at Vattikuti Urology Institute (VUI). We succeeded in creating a team and safely implemented the robotic program in our system. Adequate funding and extensive training followed by a short term proctoring are essential for this implementation.
    Matched MeSH terms: Prostatic Neoplasms/surgery
  10. Sahran S, Albashish D, Abdullah A, Shukor NA, Hayati Md Pauzi S
    Artif Intell Med, 2018 05;87:78-90.
    PMID: 29680688 DOI: 10.1016/j.artmed.2018.04.002
    OBJECTIVE: Feature selection (FS) methods are widely used in grading and diagnosing prostate histopathological images. In this context, FS is based on the texture features obtained from the lumen, nuclei, cytoplasm and stroma, all of which are important tissue components. However, it is difficult to represent the high-dimensional textures of these tissue components. To solve this problem, we propose a new FS method that enables the selection of features with minimal redundancy in the tissue components.

    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.

    Matched MeSH terms: Prostatic Neoplasms/pathology*
  11. Cheong AT, Lee PY, Ng CJ, Lee YK, Ong TA, Abdullah KL, et al.
    Sains Malaysiana, 2016;45:941-947.
    There are many treatment options for localized prostate cancer, and there is clinical equipoise in relation to the treatment outcomes. This study aimed to explore doctors’ approaches to decision support in counseling patients with localized prostate cancer in a country with a less established system of support and care delivery for cancer treatment. Four in-depth
    interviews and three focus group discussions were conducted with seven government policy makers/consultant urologists, three oncologists, four private urologists and six urology trainees in Malaysia between 2012 and 2013. Doctors facilitated the treatment decision by explaining about the disease and the treatment options, which included monitoring,
    side effects and complications of each treatment option. Paper-based (charts and diagram drawings) or electronic (ipad apps and websites) illustrations and physical models were used as patient education aids. Further reading materials and websites links were often provided to patients. Patients were given time till subsequent follow up to decide on the
    treatment and family involvement was encouraged. Referral to other healthcare professionals (oncologist, radiotherapist or other urologist) for second opinion was offered to the patients. The doctors would recommend patients to speak to prostate cancer survivors for peer support but official support groups were not easily accessible. This study highlighted
    a multi-faceted approach to support patients with localized prostate cancer in making a treatment decision. It not only involved the doctors (urologist or oncologist) themselves, but also empowered the patients and their social network to support the decision making process.
    Matched MeSH terms: Prostatic Neoplasms*
  12. Citalingam K, Abas F, Lajis NH, Othman I, Naidu R
    Molecules, 2015 Feb 17;20(2):3406-30.
    PMID: 25690296 DOI: 10.3390/molecules20023406
    Curcumin has poor in vivo absorption and bioavailability, highlighting a need for new curcumin analogues with better characteristics in these aspects. The aim of this study is to determine the anti-cancer properties of four selected curcumin analogues, on the cytotoxicity, proliferative and apoptotic effects on androgen-independent human prostate cancer cells (PC-3 and DU 145). Initial cytotoxicity screening showed MS17 has the highest cell inhibitory effect, with EC50 values of 4.4 ± 0.3 and 4.1 ± 0.8 µM, followed by MS13 (7.5 ± 0.1 and 7.4 ± 2.6 µM), MS49 (14.5 ± 1.2 and 12.3 ± 2.3 µM) and MS40E (28.0 ± 7.8 and 30.3 ± 1.9 µM) for PC-3 and DU 145 cells, respectively. Time-dependent analysis also revealed that MS13 and MS17 displayed a greater anti-proliferative effect than the other compounds. MS17 was chosen based on the high selectivity index value for further analysis on the morphological and biochemical hallmarks of apoptosis. Fluorescence microscopy analysis revealed apoptotic changes in both treated prostate cancer cells. Relative caspase-3 activity increased significantly at 48 h in PC-3 and 12 h in DU 145 cells. Highest enrichment of free nucleosomes was noted at 48 h after treatment with MS17. In conclusion, MS17 demonstrated anti-proliferative effect and induces apoptosis in a time and dose-dependent manner suggesting its potential for development as an anti-cancer agent for androgen-independent prostate cancer.
    Matched MeSH terms: Prostatic Neoplasms/drug therapy*; Prostatic Neoplasms/metabolism; Prostatic Neoplasms/pathology
  13. Nabi G, Sadiq M
    Med J Malaysia, 2002 Mar;57(1):111-3.
    PMID: 14569728
    A 56-year-old man presented with lower urinary tract obstructive symptoms, hemoptysis and progressive dyspnoea. Digital rectal examination showed an enlarged nodular prostate and a tru-cut biopsy confirmed carcinoma prostate. Chest x-ray showed multiple bilateral cannon ball opacities suggestive of metastases. He underwent bilateral orchidectomy and follow up assessment showed significant clearing of the cannon-ball lesions in the lungs. He remained asymptomatic at follow up that has extended to 8 years.
    Matched MeSH terms: Prostatic Neoplasms/pathology*; Prostatic Neoplasms/radiography; Prostatic Neoplasms/surgery*
  14. Allen NE, Travis RC, Appleby PN, Albanes D, Barnett MJ, Black A, et al.
    J Natl Cancer Inst, 2016 11;108(11).
    PMID: 27385803 DOI: 10.1093/jnci/djw153
    BACKGROUND: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade.

    METHODS: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided.

    RESULTS: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08).

    CONCLUSIONS: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.

    Matched MeSH terms: Prostatic Neoplasms/blood*; Prostatic Neoplasms/etiology; Prostatic Neoplasms/pathology*
  15. Perez-Cornago A, Appleby PN, Pischon T, Tsilidis KK, Tjønneland A, Olsen A, et al.
    BMC Med, 2017 07 13;15(1):115.
    PMID: 28701188 DOI: 10.1186/s12916-017-0876-7
    BACKGROUND: The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    METHODS: Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average of 13.9 years of follow-up, there were 7024 incident prostate cancers and 934 prostate cancer deaths.

    RESULTS: Height was not associated with total prostate cancer risk. Subgroup analyses showed heterogeneity in the association with height by tumour grade (P heterogeneity = 0.002), with a positive association with risk for high-grade but not low-intermediate-grade disease (HR for high-grade disease tallest versus shortest fifth of height, 1.54; 95% CI, 1.18-2.03). Greater height was also associated with a higher risk for prostate cancer death (HR = 1.43, 1.14-1.80). Body mass index (BMI) was significantly inversely associated with total prostate cancer, but there was evidence of heterogeneity by tumour grade (P heterogeneity = 0.01; HR = 0.89, 0.79-0.99 for low-intermediate grade and HR = 1.32, 1.01-1.72 for high-grade prostate cancer) and stage (P heterogeneity = 0.01; HR = 0.86, 0.75-0.99 for localised stage and HR = 1.11, 0.92-1.33 for advanced stage). BMI was positively associated with prostate cancer death (HR = 1.35, 1.09-1.68). The results for waist circumference were generally similar to those for BMI, but the associations were slightly stronger for high-grade (HR = 1.43, 1.07-1.92) and fatal prostate cancer (HR = 1.55, 1.23-1.96).

    CONCLUSIONS: The findings from this large prospective study show that men who are taller and who have greater adiposity have an elevated risk of high-grade prostate cancer and prostate cancer death.

    Matched MeSH terms: Prostatic Neoplasms/complications; Prostatic Neoplasms/etiology*; Prostatic Neoplasms/epidemiology
  16. Hong GE, Kong CH, Singam P, Cheok LB, Zainuddin ZM, Azrif M
    Asian Pac J Cancer Prev, 2010;11(5):1351-3.
    PMID: 21198291
    INTRODUCTION: Analysis of epidemiological as well as survival differences among the multiethnic population of Malaysia with prostate cancer is important.

    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.

    Matched MeSH terms: Prostatic Neoplasms/blood; Prostatic Neoplasms/epidemiology; Prostatic Neoplasms/pathology*; Prostatic Neoplasms/therapy
  17. 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*
  18. 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
  19. Watts EL, Appleby PN, Perez-Cornago A, Bueno-de-Mesquita HB, Chan JM, Chen C, et al.
    Eur Urol, 2018 Nov;74(5):585-594.
    PMID: 30077399 DOI: 10.1016/j.eururo.2018.07.024
    BACKGROUND: Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.

    OBJECTIVE: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.

    DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.

    RESULTS AND LIMITATIONS: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p<0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (phet=0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation.

    CONCLUSIONS: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade.

    PATIENT SUMMARY: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.

    Matched MeSH terms: Prostatic Neoplasms/blood*; Prostatic Neoplasms/epidemiology; Prostatic Neoplasms/pathology; Prostatic Neoplasms/prevention & control
  20. Sapira MK, Obiorah CC
    Med J Malaysia, 2012 Aug;67(4):417-9.
    PMID: 23082453
    Prostate cancer is a common health problem world wide. Age is its strong risk factor.
    Matched MeSH terms: Prostatic Neoplasms/pathology*
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