Head to Head Comparison of the Chun Nomogram, Percentage Free PSA and Primary Circulating Prostate Cells to Predict the Presence of Prostate Cancer at Repeat Biopsy

Murray, Nigel P,Reyes, Eduardo,Orellana, Nelson,Fuentealba, Cynthia,Jacob, Omar Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.6

Background: The limitations of total serum PSA values remain problematic, especially after an initial negative prostate biopsy. In this prospective study of Chilean men with a continued suspicion of prostate cancer due to a persistently elevated total serum PSA, abnormal digital rectal examination and initial negative prostate biopsy were compared with the use of the on-line Chun nomagram, detection of primary malignant circulating prostate cells (CPCs) and free percent PSA to predict a positive second prostate biopsy. We hypothesized that men negative for circulating prostate cells have a small risk of clinically significant prostate cancer and thus may be conservatively observed. Men positive for circulating prostate cells should undergo biopsy to confirm prostate cancer. Materials and Methods: Consecutive men with a continued suspicion of prostate cancer underwent 12 core TRUS prostate biopsy; age, total serum PSA and percentage free PSA and Chun nomagram scores were registered. Immediately before biopsy an 8ml blood simple was taken to detect primary mCPCs. Mononuclear cells were obtained by differential gel centrifugation and identified using double immunostaining with anti-PSA and anti-P504S. Biopsies were classifed as cancer/no-cancer, mCPC detecton test as negative/positive and the total number of cells/8ml registered. Areas under the curve (AUC) for percentage free PSA, Chun score and CPCs were calculated and compared. Diagnostic yields were calculated with reference to the number of possible biopsies that could be avoided and the number of clinically significant cancers that would be missed. Results: A total of 164 men underwent a second biopsy; 41 (25%) had cancer; the AUCs were 0.65 for free PSA, 0.76 for the Chun score and 0.87 for CPC detection, the last having a significantly superior prediction value (p=0.01). Using cut off values of free PSA <10%, Chun score >50% and ${\geq}1$ CPC detected, CPC detection had a higher diagnostic yield. Some 4/41 cancers complied with the criteria for active surveillance, free PSA and the Chun score missed a higher number of significant cancers when compared with CPC detection. Conclusions: Primary CPC detection outperformed the use of free PSA and the Chun nomagram in predicting clinically significant prostate cancer at repeat prostate biopsy.

p63 Cytoplasmic Aberrance is Associated with High Prostate Cancer Stem Cell Expression

Ferronika, Paranita,Triningsih, F.X. Ediati,Ghozali, Ahmad,Moeljono, Abraham,Rahmayanti, Siti,Shadrina, Arifah Nur,Naim, Awang Emir,Wudexi, Ivan,Arnurisa, Alfa Monica,Nanwani, Sandeep Tarman,Harijadi, Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Introduction: Prostate cancer in Indonesia is the $3^{rd}$ ranking cancer among males and the $5^{th}$ rank for their cancer mortality. Prognostic markers that can identify aggressive prostate cancer in early stages and help select appropriate therapy to finally reduce the mortality are therefore urgently needed. It has been suggested that stem cells in the prostate gland have a role in initiation, progression, and metastasis of cancer, although controversy continues to exist. Maintenance of normal stem cell or reserve cell populations in several epithelia including prostate has been shown to be regulated by p63 and alteration of p63 expression is considered to have an oncogenic role in prostate cancer. We hypothesize that the expression of cytoplasmic aberrance of p63 is associated with high ALDH1A1 expression as a cancer stem cell marker, thus leading to progression of prostate cancer. Methods: Using a cross-sectional study during two years (2009-2010), a total of 79 paraffin embedded tissues of benign prostatic hyperplasia, PIN prostatic intraepithelial neoplasia, low and high Gleason score prostate cancer were investigated using immunohistochemistry. Associations between cytoplasmic p63 and ALDH1A1, as well as with pathological diagnosis, were analyzed by Chi-Square test using SPSS 15.0. Links of both markers with cell proliferation rate (KI-67) and apoptotic rate (cleaved caspase 3) were also analyzed by Kruskal-Wallis test. Results: The mean age of patient at the diagnosis is 70.0 years. Cytoplasmic aberrance of p63 was associated with ALDH1A1 expression (p<0.001) and both were found to have significant relationships with pathological diagnosis (including Gleason score), (p=0.006 and p<0.001 respectively). Moreover, it was also found that higher levels of cytoplasmic p63 were significantly associated with the frequency of proliferating cells and cells undergoing apoptosis in prostate cancers (p=0.001 and p=0.016 respectively). Conclusion: p63 cytoplasmic aberrance is associated with high ALDH1A1 expression. These components are suggested to have an important role in prostate cancer progression and may be used as molecular markers.

Functional Expression of Choline Transporter-Like Protein 1 in LNCaP Prostate Cancer Cells: A Novel Molecular Target

( Iwao Saiki ),( Miki Yara ),( Tsuyoshi Yamanaka ),( Hiroyuki Uchino ),( Masato Inazu ) 한국응용약물학회 2020 Biomolecules & Therapeutics(구 응용약물학회지) Vol.28 No.2

Prostate cancer is one of the most common cancers in men. Choline PET or PET/CT has been used to visualize prostate cancer, and high levels of choline accumulation have been observed in tumors. However, the uptake system for choline and the functional expression of choline transporters in prostate cancer are not completely understood. In this study, the molecular and functional aspects of choline uptake were investigated in the LNCaP prostate cancer cell line along with the correlations between choline uptake and cell viability in drug-treated cells. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA were highly expressed in LNCaP cells. CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. [³H]Choline uptake was mediated by a single Na+-independent, intermediate-affinity transport system in the LNCaP cells. The anticancer drugs, flutamide and bicalutamide, inhibited cell viability and [3H]choline uptake in a concentration-dependent manner. The correlations between the effects of these drugs on cell viability and [3H]choline uptake were significant. Caspase-3/7 activity was significantly increased by both flutamide and bicalutamide. Furthermore, these drugs decreased CTL1 expression in the prostate cancer cell line. These results suggest that CTL1 is functionally expressed in prostate cancer cells and are also involved in abnormal proliferation. Identification of this CTL1-mediated choline transport system in prostate cancer cells provides a potential new therapeutic target for the treatment of this disease.

Comparison of the Formula of PSA, Age, Prostate Volume and Race Versus PSA Density and the Detection of Primary Malignant Circulating Prostate Cells in Predicting a Positive Initial Prostate Biopsy in Chilean Men with Suspicion of Prostate Cancer

Murray, Nigel P,Reyes, Eduardo,Fuentealba, Cynthia,Orellana, Nelson,Morales, Francisca,Jacob, Omar Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.13

Background: Combining risk factors for prostate cancer into a predictive tool may improve the detection of prostate cancer while decreasing the number of benign biopsies. We compare one such tool, age multiplied by prostate volume divided by total serum PSA (PSA-AV) with PSA density and detection of primary malignant circulating prostate cells (CPCs) in a Chilean prostate cancer screening program. The objectives were not only to determine the predictive values of each, but to determine the number of clinically significant cancers that would have been detected or missed. Materials and Methods: A prospective study was conducted of all men undergoing 12 core ultrasound guided prostate biopsy for suspicion of cancer attending the Hospital DIPRECA and Hospital de Carabineros de Chile. Total serum PSA was registered, prostate volumecalculated at the moment of biopsy, and an 8ml blood simple taken immediately before the biopsy procedure. Mononuclear cells were obtained from the blood simple using differential gel centrifugation and CPCs identified using immunocytchemistry with anti-PSA and anti-P504S. Biopsy results were classed as positive or negative for cancer and if positive the Gleason score, number of positive cores and percent infiltration recorded. Results: A total of 664 men participated, of whom 234 (35.2%) had cancer detected. They were older, had higher mean PSA, PSA density and lower PSA-AV. Detection of CPCs had high predictive score, sensitivity, sensibility and positive and negative predictive values, PSA-AV was not significantly different from PSA density in this population. The use of CPC detection avoided more biopsies and missed fewer significant cancers.Conclusions: In this screening population the use of CPC detection predicted the presence of clinically significant prostate cancer better than the other parameters. The high negative predictive value would allow men CPC negative to avoid biopsy but remain in follow up. The formula PSA-AV did not add to the predictive performance using PSA density.

울금(鬱金)이 폐암(肺癌), 자궁암(子宮癌), 신경교종(神經膠腫) 및 전립선암(前立腺癌)에 대한 세포자살유도(細胞自殺誘導)에 미치는 영향(影響)

박상현,김진성,윤상협,류봉하,Park, Sang-Hyun,Kim, Jin-Sung,Yoon, Sang-Hyub,Ryu, Bong-Ha 대한한방내과학회 2006 大韓韓方內科學會誌 Vol.27 No.2

Objectives: We are aimed to identify anti-tumor effects of Curcuma aromatics on some kinds of cancer cells through molecular biologic methods. Materials & Methods: We used 4 kinds of cancer cell lines such as lung cancer cells(AS49), cervical cancer cells(HeLa), glioma cancer cells(A172) and prostate cancer cells(PC3). We treated the boiled extract of Curcuma aromatica $5{\mu}g,\;10{\mu}g$ to cultural media(ml) for 24 hours. We measured the cytotoxicitv on 4 kinds of cancer cells through tryphan blue exclusion test and the suppressive effect on viability of 4 kinds of cancer cells via MTT assay. We measured change of mitochondria membrane potential via flow cytometry. The quantitative RT-PCR was used to examine the effect on the revelation of Bcl-2 and Bax which are genes related to apoptosis. We examined the effect on the revelation of Bcl-2 Protein and Bar protein by western blot analysis. Results : In the experiment of tryphan blue exclusion test, the extract of Curcuma aromatica showed more significant killing effect on AS49, HeLa than the control group with density dependent manner, which was statistically significant. In the experiment of MTT assay the extract of Curcuma aromatica showed more suppressive effect on viability of A549, HeLa than the control group with density dependent manner, which was statistically significant. Curcuma aromatica induced apoptosis by decreasing the membrane potential of mitochondria in A549, HeLa. In the experiment of the revelation of genes related to apoptosis, the revelation of Bcl-2 decreased and the revelation of Bax increased in A549, HeLa treated with Curcuma aromatica with dose dependent manner. In the experiment of the revelation of protein related to apoptosis, the protein levels of Bcl-2 decreased and the protein levels of Bax increased in AS49, HeLa treated with Curcuma aromatica with dose dependent manner. Conclusions: From this study, we can infer that Curcuma aromatica has anti-tumor effect on lung cancer cells and uterine carcinoma cells but not on glioma cells and prostate cancer cells.

Red Cell Distribution Width as a Predictor of Prostate Cancer Progression

Albayrak, Sebahattin,Zengin, Kursad,Tanik, Serhat,Bakirtas, Hasan,Imamoglu, Abdurrahim,Gurdal, Mesut Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.18

Background: The aims of this study were to investigate the utility of red blood cell distribution width (RDW) as a simple and readily available marker in prostate cancer, as well as to evaluate RDW as a predictor of progression in prostate cancer patients. Materials and Methods: We evaluated 62 newly diagnosed prostate cancer patients who underwent transrectal ultrasound (TRUS)-guided biopsy and 62 healthy controls of mean age 64 (range, 45-75) years at the Urology Clinic of Bozok University Hospital. Data collection was performed using our laboratory information system database to retrieve findings regarding RDW, hemoglobin, prostatespecific antigen (PSA), and age. The RDW values were compared between the healthy control group and prostate cancer patients. A high risk of progression as defined as a Gleason score (GS) >6, total number of cores positive for cancer >33%, each core containing >50% cancer cells, and a prostate-specific antigen (PSA) level >10 ng/mL. Patients were classified according to risk of progression, as well as divided into subgroups according to the RDW quartile. Results: The mean RDW value of prostate cancer patients was 14.6, compared with 13.7 in the healthy control group (p=0.001). A higher RDW was associated with an increased risk of progression, whereas a lower RDW value was correlated with a low risk of progression. Conclusions: RDW is an easily derived measure that might, in combination with other markers, help predict prostate cancer risk and progression. We suggest that RDW may be used in combination with other parameters in the assessment of prostate cancer.

Expression of Prostate Specific Antigen(PSA) by Etoposide and Androgen in Human Prostate Cancer Cells

Myeong-Seon Lee 한국엔터테인먼트산업학회 2015 한국엔터테인먼트산업학회논문지 Vol.9 No.1s

Prostate cancer(PrCa) is a leading cause of cancer-related death in man. Prostate specific antigen(PSA) is widely utilized as a marker for the diagnosis and monitoring of prostate cancer. This study examined effects of androgen 5α-dihydrotestosterone(DHT) vs DHEA and/or anticancer agent etoposide on proliferation and PSA expression of the prostate cancer LNCaP cells. A progressive increase in PSA secretion was observed at higher DHT concentration in case of 48 h treatment. compared to DHEA. Androgen played a significant role in the regulation of cellular proliferation and production of PSA in human prostate cancer LNCaP cells. In contrast with DHT, DHEA administration stimulated LNCaP cell proliferation in a time and dose-response manner, etoposide had a strong cytotoxic and apoptotic effect on LNCaP cells. Moreover, etoposide reduced cell growth and PSA expression induced by DHT and DHEA. These results demonstrate that etoposide could be a potential agent for the treatment of hormone refractory prostate cancer. Further studies of the mechanisms of DHEA will be required to discern the implication of DHEA supplementation on prostatic health because supplemental DHEA use may pose a cancer risk in patients with nascent or occult prostate cancer

Extended use of P504S Positive Primary Circulating Prostate Cell Detection to Determine the Need for Initial Prostate Biopsy in a Prostate Cancer Screening Program in Chile

Murray, Nigel P.,Reyes, Eduardo,Fuentealba, Cynthia,Jacob, Omar,Orellana, Nelson Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Background: To determine the frequency of primary circulating prostate cells (CPC) detection according to age and serum PSA levels in a cohort of men undergoing screening for prostate cancer and to determine the diagnostic yield in those men complying with the criteria for prostate biopsy. Materials and Methods: A prospective study was carried out to analyze all men evaluated in a hospital prostate cancer screening program. Primary CPCs were obtained by differential gel centrifugation and detected using standard immunocytochemistry using anti-PSA, positive samples undergoing a second process with anti-P504S. A malignant primary CPC was defined as PSA+ P504S+, and a test positive if 1 cell/4ml was detected. The frequency of primary CPC detection was compared with age and serum PSA levels. Men with a PSA >4.0ng/ml and/or abnormal rectal examination underwent 12 core prostate biopsy, and the results were registered as cancer/no-cancer and compared with the presence/absence of primary CPCs to calculate the diagnostic yield. Results: A total of 1,117 men participated; there was an association of primary CPC detection with increasing age and increasing serum PSA. Some 559 men underwent initial prostate biopsy of whom 207/559 (37.0%) were positive for primary CPCs and 183/559 (32.0%) had prostate cancer detected. The diagnostic yield of primary CPCs had a sensitivity of 88.5%, a specificity of 88.0%, and positive and negative predictive values of 78.3% and 94.9%, respectively. Conclusions: The use of primary CPCs for testing is recommended, since its high negative predictive value could be used to avoid prostate biopsy in men with an elevated PSA and/or abnormal DRE. Men positive for primary CPCs should undergo prostate biopsy. It is a test that could be implemented in the routine immunocytochemical laboratory.

Cytosine deaminase-expressing human neural stem cells inhibit tumor growth in prostate cancer-bearing mice

Lee, H.J.,Doo, S.W.,Kim, D.H.,Cha, Y.J.,Kim, J.H.,Song, Y.S.,Kim, S.U. Elsevier ; Elsevier Science Pub. Co 2013 Cancer letters Vol.335 No.1

Prostate cancer is the most common malignancy among men. Prostate cancer-related deaths are largely attributable to the development of hormone resistance in the tumor. No effective chemotherapy has yet been developed for advanced prostate cancer. It is desirable if a drug can be delivered directly and specifically to prostate cancer cells. Stem cells have selective migration ability toward cancer cells and therapeutic genes can be easily transduced into stem cells. In one form of gene therapy for cancer, the stem cells carry a gene encoding an enzyme that transforms an inert prodrug into a toxic product. Cytosine deaminase (CD) transforms the pro-drug 5-fluorocytosine into highly cytotoxic 5-fluorouracil (5-FU). The migration of the genetically modified stem cells was monitored by molecular magnetic resonance imaging, after labeling the stem cells with fluorescent magnetic nanoparticles (MNPs). Human neural stem cells encoding CD (HB1.F3.CD) were prepared and labeled with MNP. In tumor-bearing C57B mice, systemically transplanted HB1.F3.CD stem cells migrated toward the tumor and in combination with prodrug 5-FC, the volume of tumor implant was significantly reduced. These findings may contribute to development of a new selective chemotherapeutic strategy against prostate cancer.

β-glucan induces apoptosis the expression of apoptotic factors in human prostate cancer cells

김현우,고홍범 한국예방수의학회 2013 예방수의학회지 Vol.37 No.3

Prostate cancer is a leading cause of death among the aging men. Surgical or radio therapy is effective when the cancer is confined to the prostate gland but once the cancer spreads beyond the pelvis, even chemotherapy and hormonal ablation therapy fails in curing this disease. Our previous studies have shown that β-glucan induces apoptosis in prostate cancer cells. Cellular viability of these cells treated with β-glucan was measured by MTT assay. β-glucan induced dose- and time-dependent inhibition of cell viability in LNCaP cancer cells. In flow cytometry analysis, β-glucan induced dose- and time-dependent apoptotic activities in LNCaP cancer cells. In addition, increased of expression caspase-3, caspase-9, Bax, and cytochrome C but decreased of expression Bcl-2 was observed in LNCaP cells treated with β-glucan. These results suggest that β-glucan induces apoptosis in LNCaP human prostate cancer cells mediated mainly through the increased of expression caspase-3, -9, Bax, cytochrome C and decreased of expression Bcl-2.