• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4711-4715
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• 2013

Aim: The aim of this study was to evaluate acute adverse events and efficacy of three-dimensional intensitymodulated radiotherapy (IMRT) combined with endocrine therapy for intermediate and advanced prostate cancer. Methods: Sixty-seven patients were treated with three-dimensional IMRT combined with maximum androgen blockade. The correlation between radiation-induced rectal injury and clinical factors was further analyzed. Results: After treatment, 21 patients had complete remission (CR), 37 had partial remission (PR), and nine had stable disease (SD), with an overall response rate of 86.5%. The follow-up period ranged from 12.5 to 99.6 months. Thirty-nine patients had a follow-up time of ${\geq}$ five years. In this group, three-year and five-year overall survival rates were 89% and 89.5%, respectively; three-year and five-year progression-free survival rates were 72% and 63%. In univariate analyses, gross tumor volume was found to be prognostic for survival ($X^2$ = 5.70, P = 0.037). Rates of leucopenia and anemia were 91.1% and 89.5%, respectively. Two patients developed acute liver injury, and a majority of patients developed acute radiation proctitis and cystitis, mainly grade 1/2. Tumor volume before treatment was the only prognostic factor influencing the severity of acute radiation proctitis (P < 0.05). Conclusions: IMRT combined with endocrine therapy demonstrated promising efficacy and was well tolerated in patients with intermediate and advanced prostate cancer.

• Molecules and Cells
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• 제45권4호
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• pp.202-215
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• 2022

The androgen receptor (AR) is an important therapeutic target for treating prostate cancer (PCa). Moreover, there is an increasing need for understanding the AR-independent progression of tumor cells such as neuroendocrine prostate cancer (NEPC). Menin, which is encoded by multiple endocrine neoplasia type 1 (MEN1), serves as a direct link between AR and the mixed-lineage leukemia (MLL) complex in PCa development by activating AR target genes through histone H3 lysine 4 methylation. Although menin is a critical component of AR signaling, its tumorigenic role in AR-independent PCa cells remains unknown. Here, we compared the role of menin in AR-positive and AR-negative PCa cells via RNAi-mediated or pharmacological inhibition of menin. We demonstrated that menin was involved in tumor cell growth and metastasis in PCa cells with low or deficient levels of AR. The inhibition of menin significantly diminished the growth of PCa cells and induced apoptosis, regardless of the presence of AR. Additionally, transcriptome analysis showed that the expression of many metastasis-associated genes was perturbed by menin inhibition in AR-negative DU145 cells. Furthermore, wound-healing assay results showed that menin promoted cell migration in AR-independent cellular contexts. Overall, these findings suggest a critical function of menin in tumorigenesis and provide a rationale for drug development against menin toward targeting high-risk metastatic PCa, especially those independent of AR.

• Korean Journal of Radiology
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• 제21권6호
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• pp.684-694
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• 2020

Objective: The purpose was to review the diagnostic performance of the length of tumor capsular contact (LCC) on magnetic resonance imaging (MRI) for detecting prostate cancer extraprostatic extension (EPE). Materials and Methods: PubMed and EMBASE databases were searched up to March 24, 2019. We included diagnostic accuracy studies that evaluated LCC on MRI for EPE detection using radical prostatectomy specimen histopathology as the reference standard. Quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity were pooled and graphically presented using hierarchical summary receiver operating characteristic (HSROC) plots. Meta-regression and subgroup analyses were conducted to explore heterogeneity. Results: Thirteen articles with 2136 patients were included. Study quality was generally good. Summary sensitivity and specificity were 0.79 (95% confidence interval [CI] 0.73-0.83) and 0.67 (95% CI 0.60-0.74), respectively. Area under the HSROC was 0.81 (95% CI 0.77-0.84). Substantial heterogeneity was present among the included studies according to Cochran's Q-test (p < 0.01) and Higgins I² (62% and 86% for sensitivity and specificity, respectively). In terms of heterogeneity, measurement method (curvilinear vs. linear), prevalence of Gleason score ≥ 7, MRI readers' experience, and endorectal coils were significant factors (p ≤ 0.01), whereas method to determine the LCC threshold, cutoff value, magnet strength, and publication year were not (p = 0.14-0.93). Diagnostic test accuracy estimates were comparable across all assessed MRI sequences. Conclusion: Greater LCC on MRI is associated with a higher probability of prostate cancer EPE. Due to heterogeneity among the studies, further investigation is needed to establish the optimal cutoff value for each clinical setting.

• 한국응급구조학회지
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• 제24권3호
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• pp.147-154
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• 2020

Purpose: The purpose of the study was to investigate traumatic urethral injury in a 63-year-old patient with hematuria. Methods: A hematuria patient was transferred by paramedics. At the time of the visit, the patient's blood pressure (151/91mmHg), pulse rate (86/min), body temperature (37.1℃), and other vital signs were stable. Their KTAS (Korean Triage and Acuity Scale) was Level 4. The patient had no damage to the injured area, but a large contrast defect was observed between the prostate urethra and the bladder in urethral angiography performed due to persistent hematuria and pain in the injured area. Results: Following radiological evaluation of a suspected liposarcoma or neuroma mass of the prostate urethra, the mass was removed through urethral tumor resection. The result of histologic evaluation provided a diagnosis of highly differentiated invasive urethral cell carcinoma that had invaded the muscle layer. The patient was given additional treatment for urethral cancer but was rejected and is currently being followed. Conclusion: The prognosis for urinary tract cancer has distinct differences for patients with lymph node metastasis and tumor characteristics. The presence or absence of urethral cancer should be confirmed through angiography, CT, MRI, and cystoscopy.

• Toxicological Research
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• 제26권2호
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• pp.109-115
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• 2010

The purpose of this study was to elucidate the mechanism underlying enhanced radiosensitivity to $^{60}Co\;{\gamma}$-irradiation in human prostate PC-3 cells pretreated with berberine. The cytotoxic effect of the combination of berberine and irradiation was superior to that of berberine or irradiation alone. Cell death and Apoptosis increased significantly with the combination of berberine and irradiation. Additionally, ROS generation was elevated by berberine with or without irradiation. The antioxidant NAC inhibited berberine and radiation-induced cell death. Bax, caspase-3, p53, p38, and JNK activation increased, but activation of Bcl-2, ERK, and HO-1 decreased with berberine treatment with or without irradiation. Berberine inhibited the anti-apoptotic signal pathway involving the activation of the HO-1/NF-${\kappa}B$-mediated survival pathway, which prevents radiation-induced cell death. Our data demonstrate that berberine inhibited the radioresistant effects and enhanced the radiosensitivity effects in human prostate cancer cells via the MAPK/caspase-3 and ROS pathways.

• 한국정보과학회논문지:컴퓨팅의 실제 및 레터
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• 제15권9호
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• pp.700-704
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• 2009

본 논문은 영상보정 및 다단계 정합을 통한 전립선의 MR 영상과 병리 영상 간의 융합방법을 제안한다. 제안 방법은 영상보정, 강체 정합, 비강체 정합, 영상융합의 네 단계로 이루어진다. 첫째, 영상보정 단계에서 T2 MR 강조 영상의 출혈 부위의 자기값을 T1 MR 강조 영상의 자기값으로 대체시키고, 2, 4장으로 분리된 병리 영상을 한장의 영상으로 만든 후 MR 영상과 동일한 해상도로 줄인다. 둘째, 전립선의 T2 MR 강조 영상과 병리 영상 간에 자기간의 상호정보를 최적화하는 강체변환을 구한다. 셋째, TPS 와핑을 이용하여 병리 영상의 전립선 부위가 T2 MR 강조 영상의 전립선 부위에 정합되는 비강체변환을 구한다. 넷째, MR 영상과 변환을 적용시킨 병리 영상을 융합한다. 실험 결과 영상보정 및 다단계 정합 후의 전립선의 T2 MR 강조 영상과 병리 영상의 간의 평균 거리 오차는 0.8815 mm였고, 두 영상의 융합을 통해 T2 MR 강조 영상에서 전립선 암의 위치를 정확하게 볼 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1879-1883
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• 2014

Background: The relationship between obesity and prostate cancer aggressiveness is controversial in recent studies, partly because BMI is the only generally applied marker of obesity. Our study aimed at evaluating the correlation of periprostatic fat (PF) on magnatic resonance imaging (MRI) and adipocytokines with prostate cancer aggressiveness. Patients and method: A total of 184 patients who underwent radical retropubic prostatectomy (RRP) were analyzed retrospectively; different fat measurements on MRI slices and levels of adipocytokines were compared with the clinical and pathologic factors using SSPS ver.13.0. Result: The PF rates showed a statistically significant variation (p=0.019, 0.025) among groups, that is to say, more adipose tissue was distributed in periprostatic areas of high risk patients. Logistic regression analysis adjusted for age revealed a statistically association between the PF, the ratio and the risk of having high-risk disease (p=0.031, 0.024). The levels of IL-6, leptin and c-reactive protein (CRP) significantly increased with the aggressiveness of prostate cancer, and also with PF and its ratio. The strongest correlation was seen between IL-6 and PF (Pearson r coefficient=0.67, P<0.001). No association was observed between adipocytokines and BMI. Conclusion: Periprostatic adiposity not only affects prostate cancer aggressiveness, but also influences the secretion of adipocytokines. IL-6, PF and CRP have promoting effects on progression of prostate cancer.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2000년도 International Symposium on Bioinformatics
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• pp.74-82
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• 2000

Prostate cancer initially responds and regresses in response to androgen depletion therapy, but most human prostate cancers will eventually recur, and re-grow as an androgen independent tumor. Once these tumors become hormone refractory, they usually are incurable leading to death for the patient. Little is known about the molecular details of how prostate cancer cells regress following androgen ablation and which genes are involved in the androgen independent growth following the development of resistance to therapy. Such knowledge would reveal putative drug targets useful in the rational therapeutic design to prevent therapy resistance and control androgen independent growth. The application of genome scale technologies have permitted new insights into the molecular mechanisms associated with these processes. Specifically, we have applied functional genomics using high density cDNA microarray analysis for parallel gene expression analysis of prostate cancer in an experimental xenograft system during androgen withdrawal therapy, and following therapy resistance, The large amount of expression data generated posed a formidable bioinformatics challenge. A novel template based gene clustering algorithm was developed and applied to the data to discover the genes that respond to androgen ablation. The data show restoration of expression of androgen dependent genes in the recurrent tumors and other signaling genes. Together, the discovered genes appear to be involved in prostate cancer cell growth and therapy resistance in this system. We have also developed and applied tissue microarray (TMA) technology for high throughput molecular analysis of hundreds to thousands of clinical specimens simultaneously. TMA analysis was used for rapid clinical translation of candidate genes discovered by cDNA microarray analysis to determine their clinical utility as diagnostic, prognostic, and therapeutic targets. Finally, we have developed a bioinformatic approach to combine pharmacogenomic data on the efficacy and specificity of various drugs to target the discovered prostate cancer growth associated candidate genes in an attempt to improve current therapeutics.

• Korean Journal of Radiology
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• 제24권6호
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• pp.574-589
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• 2023

Radiopharmaceuticals targeting prostate-specific membrane antigens (PSMA) are essential for the diagnosis, evaluation, and treatment of prostate cancer (PCa), particularly metastatic castration-resistant PCa, for which conventional treatment is ineffective. These molecular probes include [⁶⁸Ga]PSMA, [¹⁸F]PSMA, [Al¹⁸F]PSMA, [^99mTc]PSMA, and [⁸⁹Zr]PSMA, which are widely used for diagnosis, and [¹⁷⁷Lu]PSMA and [²²⁵Ac]PSMA, which are used for treatment. There are also new types of radiopharmaceuticals. Due to the differentiation and heterogeneity of tumor cells, a subtype of PCa with an extremely poor prognosis, referred to as neuroendocrine prostate cancer (NEPC), has emerged, and its diagnosis and treatment present great challenges. To improve the detection rate of NEPC and prolong patient survival, many researchers have investigated the use of relevant radiopharmaceuticals as targeted molecular probes for the detection and treatment of NEPC lesions, including DOTA-TOC and DOTA-TATE for somatostatin receptors, 4A06 for CUB domain-containing protein 1, and FDG. This review focused on the specific molecular targets and various radionuclides that have been developed for PCa in recent years, including those mentioned above and several others, and aimed to provide valuable up-to-date information and research ideas for future studies.

• Biomolecules & Therapeutics
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• 제29권6호
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• pp.667-677
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• 2021

The elevated expression of the hyaluronan-mediated motility receptor (HMMR) is known to be highly associated with tumor progression in prostate cancer, but the molecular mechanisms underlying the regulation of HMMR expression remain unclear. Here, we report that mammalian target of rapamycin (mTOR) is a key regulator of HMMR expression, for which its kinase activity is required. Pharmacological inhibitors of mTOR, such as rapamycin and Torin2, markedly suppressed the mRNA level as well as the protein level of HMMR in LNCaP and PC-3 cells. Our data demonstrate that such regulation occurs at the transcription level. HMMR promoter reporter assays revealed that the transcription factor SRF is responsible for the mTOR-mediated transcriptional regulation of HMMR gene. Consistently, the suppression of HMMR expression by Torin2 was noticeably reversed by the overexpression of SRF. Moreover, our findings suggest that the SRF binding sites responsible for the transcriptional regulation of HMMR through the mTOR-SRF axis are located in HMMR promoter sequences carrying the first intron, downstream of the translational start site. Furthermore, the upregulation of HMMR by DHT was abolished by stimulation with rapamycin, prior to DHT treatment, suggesting that mTOR activity is required for the induction of HMMR expression by androgen. Collectively, our study provides new mechanistic insights into the role of mTOR/SRF/AR signaling in HMMR regulation in prostate cancer cells.