Displaying publications 41 - 60 of 197 in total

Abstract:
Sort:
  1. Yahya N, Ebert MA, House MJ, Kennedy A, Matthews J, Joseph DJ, et al.
    Int J Radiat Oncol Biol Phys, 2017 02 01;97(2):420-426.
    PMID: 28068247 DOI: 10.1016/j.ijrobp.2016.10.024
    PURPOSE: We assessed the association of the spatial distribution of dose to the bladder surface, described using dose-surface maps, with the risk of urinary dysfunction.

    METHODS AND MATERIALS: The bladder dose-surface maps of 754 participants from the TROG 03.04-RADAR trial were generated from the volumetric data by virtually cutting the bladder at the sagittal slice, intersecting the bladder center-of-mass through to the bladder posterior and projecting the dose information on a 2-dimensional plane. Pixelwise dose comparisons were performed between patients with and without symptoms (dysuria, hematuria, incontinence, and an International Prostate Symptom Score increase of ≥10 [ΔIPSS10]). The results with and without permutation-based multiple-comparison adjustments are reported. The pixelwise multivariate analysis findings (peak-event model for dysuria, hematuria, and ΔIPSS10; event-count model for incontinence), with adjustments for clinical factors, are also reported.

    RESULTS: The associations of the spatially specific dose measures to urinary dysfunction were dependent on the presence of specific symptoms. The doses received by the anteroinferior and, to lesser extent, posterosuperior surface of the bladder had the strongest relationship with the incidence of dysuria, hematuria, and ΔIPSS10, both with and without adjustment for clinical factors. For the doses to the posteroinferior region corresponding to the area of the trigone, the only symptom with significance was incontinence.

    CONCLUSIONS: A spatially variable response of the bladder surface to the dose was found for symptoms of urinary dysfunction. Limiting the dose extending anteriorly might help reduce the risk of urinary dysfunction.

    Matched MeSH terms: Prostatic Neoplasms/radiotherapy*
  2. Nalairndran G, Chung I, Abdul Razack AH, Chung FF, Hii LW, Lim WM, et al.
    J Cell Mol Med, 2021 Sep;25(17):8187-8200.
    PMID: 34322995 DOI: 10.1111/jcmm.16684
    Prostate cancer (PCa) is the second most common malignancy and is the fifth leading cause of cancer mortality among men globally. Docetaxel-based therapy remains the first-line treatment for metastatic castration-resistant prostate cancer. However, dose-limiting toxicity including neutropenia, myelosuppression and neurotoxicity is the major reason for docetaxel dose reductions and fewer cycles administered, despite a recent study showing a clear survival benefit with increased total number of docetaxel cycles in PCa patients. Although previous studies have attempted to improve the efficacy and reduce docetaxel toxicity through drug combination, no drug has yet demonstrated improved overall survival in clinical trial, highlighting the challenges of improving the activity of docetaxel monotherapy in PCa. Herein, we identified 15 lethality hits for which inhibition could enhance docetaxel sensitivity in PCa cells via a high-throughput kinome-wide loss-of-function screen. Further drug-gene interactions analyses identified Janus kinase 1 (JAK1) as a viable druggable target with existing experimental inhibitors and FDA-approved drugs. We demonstrated that depletion of endogenous JAK1 enhanced docetaxel-induced apoptosis in PCa cells. Furthermore, inhibition of JAK1/2 by baricitinib and ruxolitinib synergizes docetaxel sensitivity in both androgen receptor (AR)-negative DU145 and PC3 cells, but not in the AR-positive LNCaP cells. In contrast, no synergistic effects were observed in cells treated with JAK2-specific inhibitor, fedratinib, suggesting that the synergistic effects are mainly mediated through JAK1 inhibition. In conclusion, the combination therapy with JAK1 inhibitors and docetaxel could be a useful therapeutic strategy in the treatment of prostate cancers.
    Matched MeSH terms: Prostatic Neoplasms/drug therapy*
  3. Qi Qi C, Ajit Singh V
    BMJ Case Rep, 2012;2012.
    PMID: 22892228 DOI: 10.1136/bcr.01.2012.5518
    The authors present an interesting case under our follow-up who has had five different forms of tumours with different pathologies throughout his lifetime. He started off with hepatoma, followed by pleomorphic sarcoma of the thigh, adenocarcinoma of the prostate, meningioma and finally schwanoma. He is still alive to this date.
    Matched MeSH terms: Prostatic Neoplasms/diagnosis; Prostatic Neoplasms/pathology*; Prostatic Neoplasms/therapy
  4. Lee ST, Wong PF, Cheah SC, Mustafa MR
    PLoS One, 2011;6(4):e18915.
    PMID: 21541327 DOI: 10.1371/journal.pone.0018915
    Alpha-tomatine (α-tomatine) is the major saponin in tomato (Lycopersicon esculentum). This study investigates the chemopreventive potential of α-tomatine on androgen-independent human prostatic adenocarcinoma PC-3 cells.
    Matched MeSH terms: Prostatic Neoplasms/enzymology; Prostatic Neoplasms/metabolism*; Prostatic Neoplasms/pathology*
  5. Lee YK, Lee PY, Cheong AT, Ng CJ, Abdullah KL, Ong TA, et al.
    PLoS One, 2015;10(11):e0142812.
    PMID: 26559947 DOI: 10.1371/journal.pone.0142812
    AIM: To explore the views of Malaysian healthcare professionals (HCPs) on stakeholders' decision making roles in localized prostate cancer (PCa) treatment.
    METHODS: Qualitative interviews and focus groups were conducted with HCPs treating PCa. Data was analysed using a thematic approach. Four in-depth interviews and three focus group discussions were conducted between December 2012 and March 2013 using a topic guide. Interviews were audio-recorded, transcribed verbatim, and analysed thematically.
    FINDINGS: The participants comprised private urologists (n = 4), government urologists (n = 6), urology trainees (n = 6), government policy maker (n = 1) and oncologists (n = 3). HCP perceptions of the roles of the three parties involved (HCPs, patients, family) included: HCP as the main decision maker, HCP as a guide to patients' decision making, HCP as a facilitator to family involvement, patients as main decision maker and patient prefers HCP to decide. HCPs preferred to share the decision with patients due to equipoise between prostate treatment options. Family culture was important as family members often decided on the patient's treatment due to Malaysia's close-knit family culture.
    CONCLUSIONS: A range of decision making roles were reported by HCPs. It is thus important that stakeholder roles are clarified during PCa treatment decisions. HCPs need to cultivate an awareness of sociocultural norms and family dynamics when supporting non-Western patients in making decisions about PCa.
    Matched MeSH terms: Prostatic Neoplasms
  6. Heng SP, Low SH, Sivamany K
    Indian J Cancer, 2015 Oct-Dec;52(4):639-44.
    PMID: 26960504 DOI: 10.4103/0019-509X.178386
    The purpose of this study is to determine the influence of bladder and bowel preparation protocols on the dose-volume histograms (DVHs) of these organs using the cone beam computed tomography (CBCT)-based intensity modulated radiotherapy (IMRT) treatment planning for prostate cancer patients. The pelvic DVHs of 12 prostate cancer patients were studied using CBCT images obtained immediately before each treatment. Six patients had bladder and bowel preparation protocol whilst the other six patients were the control group. Contoured bladder and rectal volumes on CBCT images were compared with planning computed tomography. All patients were treated with IMRT with 7800 cGy in 39 fractions over 8 weeks. Compared with the patient with bladder preparation protocol, patients without bladder preparation instruction had higher bladder volume and dose variation. The maximum variation in bladder volume was as high as 98% in the control group. Without bowel preparation protocol, the rectal volumes were more variability. Owing to changes in rectal filling on the day of treatment, the maximum variation in rectal volume was as high as + 96%. With bowel preparation protocol, the maximum rectum volume variations were less than 25%. The changes in prostate target dose compared with planning dose were minimal as would be expected from positioning with daily image guidance and gold seed implanted.
    Matched MeSH terms: Prostatic Neoplasms
  7. Liu Y, Uemura H, Ye D, Lee JY, Chiong E, Pu YS, et al.
    Prostate Int, 2019 Sep;7(3):108-113.
    PMID: 31485435 DOI: 10.1016/j.prnil.2018.12.001
    Background: The incidence of prostate cancer (PC) in Asian countries is increasing for reasons that are not clear. Data describing how PC is diagnosed and treated are fragmented across Asia, with marked intercountry and intracountry differences in outcome and knowledge gaps in clinical diagnostic and treatment practices. To address these knowledge gaps, we have established a PC disease registry with the aim of providing a comprehensive picture of PC diagnosis, prognosis, treatment and outcome, population characteristics, and comorbidities in real-world clinical practice in Asia.

    Methods: This is a multinational, multicenter, longitudinal, and observational registry of PC patients presenting to participating tertiary-care hospitals in eight Asian countries (www.clinicaltrials.gov NCT02546908. Registry Identifier: NOPRODPCR4001). Approximately 3500-4000 eligible patients with existing or newly diagnosed high-risk localized PC (cohort 1), nonmetastatic biochemically recurrent PC (cohort 2), or metastatic PC (cohort 3) will be consecutively enrolled and followed-up for 5 years. An enrollment cap of 600 patients each will be applied to cohorts 1 and 2. Disease status is collected at enrollment, and outcome variables captured at 3-monthly intervals include diagnostic/staging, treatments including reason for change, laboratory results, comorbidities, and concomitant medications. Treatments and survival outcomes will be captured real time until study end. Patient-reported quality-of-life will be measured every 6 months, and medical resource utilization summarized at study end. Data analysis will include exploratory analyses of potential associations between multiple risk factors and socioeconomic variables with disease progression and evaluation of various treatments for PC including novel therapies on clinical outcome and health-related quality-of-life outcomes.

    Results: 3636 men with PC were enrolled until July 2018; 416 in cohort 1, 399 in cohort 2 and 2821 in cohort 3.

    Discussion: A total of 3636 patients were enrolled until July 2018. The prospective disease registry will provide comprehensive and wide-ranging real-world information on how PC is diagnosed and treated in Asia. Such information can be used to inform policy development for best practice and direct clinical study design evaluating new treatments.

    Matched MeSH terms: Prostatic Neoplasms
  8. 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
  9. Yahya N, Manan HA
    Support Care Cancer, 2021 Jun;29(6):3035-3047.
    PMID: 33040284 DOI: 10.1007/s00520-020-05808-z
    BACKGROUND: Proton therapy (PT), frequently utilised to treat paediatric brain tumour (PBT) patients, eliminates exit dose and minimises dose to healthy tissues that theoretically can mitigate treatment-related effects including cognitive deficits. As clinical outcome data are emerging, we aimed to systematically review current evidence of cognitive changes following PT of PBT.

    MATERIALS AND METHODS: We searched PubMed and Scopus electronic databases to identify eligible reports on cognitive changes following PT of PBT according to PRISMA guidelines. Reports were extracted for information on demographics and cognitive outcomes. Then, they were systematically reviewed based on three themes: (1) comparison with photon therapy, (2) comparison with baseline cognitive measures, to population normative mean or radiotherapy-naïve PBT patients and (3) effects of dose distribution to cognition.

    RESULTS: Thirteen reports (median size (range): 70 (12-144)) were included. Four reports compared the cognitive outcome between PBT patients treated with proton to photon therapy and nine compared with baseline/normative mean/radiotherapy naïve from which two reported the effects of dose distribution. Reports found significantly poorer cognitive outcome among patients treated with photon therapy compared with proton therapy especially in general cognition and working memory. Craniospinal irradiation (CSI) was consistently associated with poorer cognitive outcome while focal therapy was associated with minor cognitive change/difference. In limited reports available, higher doses to the hippocampus and temporal lobes were implicated to larger cognitive change.

    CONCLUSION: Available evidence suggests that PT causes less cognitive deficits compared with photon therapy. Children who underwent focal therapy with proton were consistently shown to have low risk of cognitive deficit suggesting the need for future studies to separate them from CSI. Evidence on the effect of dose distribution to cognition in PT is yet to mature.

    Matched MeSH terms: Prostatic Neoplasms
  10. Xue J, Chen K, Hu H, Gopinath SCB
    PMID: 33988271 DOI: 10.1002/bab.2193
    Prostate cancer is one of the predominant cancers affecting men and has been widely reported. In the past, various therapies and drugs have been proposed to treat prostate cancer. Among these treatments, gene therapy has been considered to be an optimal and widely applicable treatment. Furthermore, due to the increased specificity of gene sequence complementation, the targeted delivery of complementary gene sequences may represent a useful treatment in certain instances. Various gene therapies, including tumor-suppressor gene therapy, suicide gene therapy, immunomodulation gene therapy and anti-oncogene therapies, have been established to treat a wide range of diseases, such as cardiac disease, cystic fibrosis, HIV/AIDS, diabetes, hemophilia, and cancers. To this end, several gene therapy clinical trials at various phases are underway. This overview describes the developments and progress in gene therapy, with a special focus being placed on prostate cancer.
    Matched MeSH terms: Prostatic Neoplasms
  11. Mohammed Faez Baobaid, Mohammed A. Abdalqader, Hasanain Faisal Ghazi, Hesham Shebl, Haitham Assem Abdalrazak
    MyJurnal
    Introduction: Prostate cancer is one of the most common causes of cancer deaths among men worldwide. In Ma- laysia however, it is the fifth leading cause of cancer among men. The increases of prostate cancer among men in Malaysia due to its close association with lack of awareness, poor knowledge and attitude. Therefore, this study is to obtain information on the prostate in terms of the level of awareness, perception, and the practice of prevention of prostate cancer among Malaysians, particularly residents of PPR Lembah Subang 1. Methods: A cross-sectional survey was collected among 200 respondents aged 18 years and above in PPR Lembah Subang 1 consisting of 37 questions comprised of socio-demographic data, source of information, risk factors, knowledge on prostate cancers, attitude on prostate cancer and practice of prevention. Likert scale scoring system used in this research. Results: Men in PPR Lembah Subang 1, show a significant association between knowledge on prostate cancer with age group, level of education, and family history showing (p value:
    Matched MeSH terms: Prostatic Neoplasms
  12. Bradley, Sani SFA, Shafiqah ASS, Collins SM, Hugtenburg RP, Rashid HAA, et al.
    Appl Radiat Isot, 2018 Aug;138:65-72.
    PMID: 28427834 DOI: 10.1016/j.apradiso.2017.04.019
    Using tailor-made sub-mm dimension doped-silica fibres, thermoluminescent dosimetric studies have been performed for α-emitting sources of 223RaCl2 (the basis of the Bayer Healthcare product Xofigo®). The use of 223RaCl2 in the palliative treatment of bone metastases resulting from late-stage castration-resistant prostate cancer focuses on its favourable uptake in metabolically active bone metastases. Such treatment benefits from the high linear energy transfer (LET) and associated short path length (<100µm) of the α-particles emitted by 223Ra and its decay progeny. In seeking to provide for in vitro dosimetry of the α-particles originating from the 223Ra decay series, investigation has been made of the TL yield of various forms of Ge-doped SiO2 fibres, including photonic crystal fibre (PCF) collapsed, PCF uncollapsed, flat and single-mode fibres. Irradiations of the fibres were performed at the UK National Physical Laboratory (NPL). Notable features are the considerable sensitivity of the dosimeters and an effective atomic number Zeff approaching that of bone, the glass fibres offering the added advantage of being able to be placed directly into liquid. The outcome of present research is expected to inform development of doped fibre dosimeters of versatile utility, including for applications as detailed herein.
    Matched MeSH terms: Prostatic Neoplasms, Castration-Resistant
  13. Ellyda, M.N., Mohd Shafie, A.
    MyJurnal
    Metastatic spread of tumors to the skull is quite unusual and often represents diagnostic and therapeutic issues. Skull involvement can be observed in various neoplasms of epithelial origin and are most often due to lung, breast, thyroid, kidney and prostate cancers. However, skull metastases from hepatocellular carcinoma (HCC) have been rarely reported. The prognosis for patients with hepatocellular carcinoma is so poor that treatment of such distant metastatic lesion cannot be achieved before death occurs due to the primary malignancy. Therefore, the clinical manifestations of cranial metastasis prior to that of primary hepatocellular carcinoma have rarely been reported. This case illustrates a rare case of skull metastasis as an initial manifestation of hepatocellular carcinoma. Although a solitary skull metastasis prior to the diagnosis of HCC demonstrates rare metastatic behavior for HCC, especially in Asia, skull metastases from HCC should be included in the differential diagnosis of skull tumors, even if the patient is asymptomatic of liver cirrhosis.
    Matched MeSH terms: Prostatic Neoplasms
  14. Hamzah AB, Choo YM, Hassali MA, Saleem F, Verma AK
    J Clin Diagn Res, 2017 Jan;11(1):XD01-XD02.
    PMID: 28274032 DOI: 10.7860/JCDR/2017/22582.9313
    Disseminated Intravascular Coagulation (DIC) develops in patient with prostate cancer, which is manifested by systemic, intracranial, intracavitary or intracutaneous bleeding indicating uncompensated or excessive fibrinolysis (XFL). This case report is a description of a 61-year-old male with metastatic prostate cancer that progressed to manifest DIC. The condition is rare in clinical practice, and even rarer when is coupled with XFL. Treatment was mainly replenishing coagulation factors, platelets and controlling the disease progression with aggressive hormonal therapy. The patient progressed to coagulopathy further with fibrinolysis, hence leading to mortality. This case study discusses the pathophysiology of this complication and various methods to monitor the disease progression are discussed.
    Matched MeSH terms: Prostatic Neoplasms
  15. Nenny Noorina Saaid, Reena Rahayu Md Zin, Siti Aishah Md Ali, Sharifah Noor Akmal Syed Hussain, Zulkifli Zainuddin, Zubaidah Zakaria
    Sains Malaysiana, 2014;43:1317-1326.
    The identification of chromosomal aberrations in prostate cancer has been widely studied with several known oncogenes and tumor suppressor genes have successfully been discovered. The most frequent aberrations detected in western population were losses in chromosome 5q, 6q, 8p, 13q, 16q, 17p, 18q and gains of 7p/q and 8q. The purpose of this study was to determine the chromosomal aberrations among Malaysian men of Southeast Asia population and discover those potential genes within that chromosomal aberrant region. Thirty-six formalin-fixed paraffin embedded specimens consist of eight organ-confined prostate cancer cases, five with capsular invasion, 14 showed metastasis and nine cases had no tumor stage recorded, were analyzed by array CGH technique. Chromosomal losses were frequently detected at 4q, 6q, 8p, 13q, 18q while gains at 7q, 11q, 12p, 16q and 17q. Gain of 16q24.3 was statistically significant with tumor size. Gains of 6q25.1 and Xq12 as well as losses of 3p13-p1.2 and 13q33.1-q33.3 were significantly correlated with Gleason grade whereas 12p13.31 gain was associated with bone metastasis. Several potential genes have also been found within that aberrant region which is myopodin (4q26-q27), ROBO1 (3p13-p11.2), ERCC5 (13q33.1-q33.3) and CD9 (12p13.31), suggesting that these genes may play a role in prostate cancer progression. The chromosomal aberrations identified by array CGH analysis could provide important clues to discover potential genes associated with prostate tumorigenesis of Malaysian men.
    Matched MeSH terms: Prostatic Neoplasms
  16. Mohd Rohaizad Md Roduan, Norhafizah Mohtarrudin, Chong PP, Malina Osman, Noraini Mohd Dusa
    Sains Malaysiana, 2015;44:727-733.
    Inflammation plays an important role to the process of prostate carcinogenesis by increasing the rate of cell proliferation,
    which contributes to an aggressive tumour phenotype. Cyclooxygenase-2 (COX-2) has been found overexpressed in
    various types of cancer cells including prostate. The aim of this study was to investigate the COX-2 expressions in different
    types of human prostate tissues. Paraffin-embedded prostate tissues from 263 samples were examined for the expression
    of COX-2 marker by immunohistochemistry method. COX-2 was found highly expressed in prostate adenocarcinoma
    (p=0.001) as compared to benign and normal tissues. The score of COX-2 expressions in most of normal prostate was
    weak 49 (77.8%), while only 16 (16%) of BPH showed strong expression. 56 cases (56%) prostate cancer showed strong
    COX-2 expression. Prostate cancer cases showed significant differences in staining patterns as tumour grade increased.
    In addition, COX-2 expression was significantly correlated with Gleason score in cancerous tissues. This study suggests
    that COX-2 overexpression is associated with prostate cancer and higher grade tumour.
    Matched MeSH terms: Prostatic Neoplasms
  17. 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*
  18. Suparji NS, Chan G, Sapili H, Arshad NM, In LL, Awang K, et al.
    PLoS One, 2016;11(3):e0151472.
    PMID: 26974436 DOI: 10.1371/journal.pone.0151472
    Geranylated 4-phenylcoumarins, DMDP-1 & -2 isolated from Mesua elegans were investigated for anticancer potential against human prostate cancer cells. Treatment with DMDP-1 & -2 resulted in cell death in a time and dose dependent manner in an MTT assay on all cancer cell lines tested with the exception of lung adenocarcinoma cells. DMDP-1 showed highest cytotoxic efficacy in PC-3 cells while DMDP-2 was most potent in DU 145 cells. Flow cytometry indicated that both coumarins were successful to induce programmed cell death after 24 h treatment. Elucidation on the mode-of-action via protein arrays and western blotting demonstrated death induced without any significant expressions of caspases, Bcl-2 family proteins and cleaved PARP, thus suggesting the involvement of caspase-independent pathways. In identifying autophagy, analysis of GFP-LC3 showed increased punctate in PC-3 cells pre-treated with CQ and treated with DMDP-1. In these cells decreased expression of autophagosome protein, p62 and cathepsin B further confirmed autophagy. In contrary, the DU 145 cells pre-treated with CQ and treated with DMDP-2 has reduced GFP-LC3 punctate although the number of cells with obvious GFP-LC3 puncta was significantly increased in the inhibitor-treated cells. The increase level of p62 suggested leakage of cathepsin B into the cytosol to trigger potential downstream death mediators. This correlated with increased expression of cathepsin B and reduced expression after treatment with its inhibitor, CA074. Also auto-degradation of calpain-2 upon treatment with DMDP-1 &-2 and its inhibitor alone, calpeptin compared with the combination treatment, further confirmed involvement of calpain-2 in PC-3 and DU 145 cells. Treatment with DMDP-1 & -2 also showed up-regulation of total and phosphorylated p53 levels in a time dependent manner. Hence, DMDP-1 & -2 showed ability to activate multiple death pathways involving autophagy, lysosomal and endoplasmic reticulum death proteins which could potentially be manipulated to develop anti-cancer therapy in apoptosis resistant cells.
    Matched MeSH terms: Prostatic Neoplasms/enzymology*; Prostatic Neoplasms/pathology*
  19. Yahya N, Ebert MA, Bulsara M, House MJ, Kennedy A, Joseph DJ, et al.
    Med Phys, 2016 May;43(5):2040.
    PMID: 27147316 DOI: 10.1118/1.4944738
    Given the paucity of available data concerning radiotherapy-induced urinary toxicity, it is important to ensure derivation of the most robust models with superior predictive performance. This work explores multiple statistical-learning strategies for prediction of urinary symptoms following external beam radiotherapy of the prostate.
    Matched MeSH terms: Prostatic Neoplasms/complications; Prostatic Neoplasms/radiotherapy*
  20. Wong PF, Abubakar S
    Oncol Rep, 2010 Jun;23(6):1501-16.
    PMID: 20428803
    The normally high concentration of zinc in normal prostate gland is significantly reduced in malignant prostate tissues, but its precise role in prostate tumorigenesis remains unclear. The present study investigates the growth and transcriptional responses of LNCaP prostate cancer cells to prolonged high Zn2+ treatment. Restoration of high intracellular Zn2+ to LNCaP cells significantly reduced the cell proliferation rate by 42.2+/-7.4% at the exponential growth phase and the efficiency of colony formation on soft agar by 87.2+/-2.5% at week 5 post-treatment. At least 161 LNCaP cell genes responded to the high intracellular Zn2+, including approximately 10.6% genes that negatively regulate cell growth and approximately 16.1% genes that promote cancer cell proliferation. Inhibition of cell growth was transient as normal proliferation rate and colony formation efficiency were restored later even in the continuous presence of high intracellular Zn2+. RT-qPCR showed constitutively higher expression levels of FBL, CD164 and STEAP1 in LNCaP cells. FBL and CD164 were responsive to the treatment with Zn2+ in PNT2 prostate normal cells and were further overexpressed in the prolonged Zn2+-treated LNCaP cells. These observations suggest that in general high Zn2+ has suppressive effects on prostate cancer cell growth but continuous exposure to an environment of high Zn2+ can lead to the overexpression of cancer promoting genes such as FBL and CD164. This could be the antagonistic mechanism used to overcome the initial cell growth inhibitory effects of high Zn2+. These findings support a potential detrimental role of Zn2+ in prostate cancer.
    Matched MeSH terms: Prostatic Neoplasms/drug therapy; Prostatic Neoplasms/metabolism*
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links