5알파 환원효소억제제 복용 후 혈중 전립선특이항원의 변화

김현우(Hyeon Woo Kim),하홍구(Hong Koo Ha) 대한비뇨기종양학회 2012 대한비뇨기종양학회지 Vol.10 No.2

The aim of this review is to provide a discussion of serum prostate specific antigen (PSA) after use of 5α-reductase inhibitors (5αRIs). The 5αRIs that are used to treat benign prostatic hyperplasia may reduce operation risks and acute urinary retention. However, it causes alteration of serum PSA level requiring clinician’s attention. After two large studies, Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study, many literatures has showed that 5αRI reduces the prevalence of prostate cancer, especially in low grade cancer. However, the incidence of high grade prostate cancer increased in 5αRI group than placebo group. Recently, some authors revealed that serum PSA sensitivity to prostate cancer increased in the 5αRIs arm than placebo using serum PSA doubling rule, serum PSA density and increasing serum PSA after nadir level. The serum PSA is usually doubled in patients with 5αRIs more than 12 months because these decrease serum PSA level down to approximately 50% at 1 year compared to baseline. It seems to be such a simple method but may yield serum PSA overestimation during first 6 months and underestimation after 4 years of the use of 5αRIs. Some authors have reported serum PSA density is useful in increasing sensitivity to prostate cancer after 1 year use of 5αRI that reduce serum PSA noising effect of benign prostatic hyperplasia. Recently, increasing serum PSA after nadir level has been seemed to be an attractive method to detect prostate cancer in patients with use of 5αRIs.

전이성 전립선암 환자에서 항남성 호르몬 요법의 예후 인자

김정남(Jung Man Kim),이창렬(Chang Yell Lee),하홍구(Hong Koo Ha),정문기(Moon Kee Chung) 대한비뇨기종양학회 2006 대한비뇨기종양학회지 Vol.4 No.4

Reactive Oxygen Species Mediates Lysophosphatidic Acid-induced Migration of SKOV-3 Ovarian Cancer Cells

Eun Kyoung Kim(김은경),Hye Sun Lee(이혜선),Hong Koo Ha(하홍구),Sung Ji Yun(윤성지),Jung Min Ha(하정민),Young Whan Kim(김영환),In Hye Jin(진인혜),Hwa Kyoung Shin(신화경),Sun Sik Bae(배순식) 한국생명과학회 2012 생명과학회지 Vol.22 No.12

세포의 이동은 성장, 면역 작용, 그리고 혈관 신생 등 많은 생리현상에 중요한 역할을 한다. 또한 염증 및 종양세포 침윤 등의 다양한 병리적 현상과도 밀접한 연관이 있다. 본 연구에서는 lysophosphatidic acid (LPA)는 활성산소의 생성을 통해 SKOV-3 난소암세포의 이동을 조절한다는 것을 관찰하였다. 먼저, 난소 암세포인 SKOV-3에서 LPA에 의한 세포의 이동이 강하게 일어남을 확인하였다. LPA에 의한 SKOV-3 세포의 이동은 phosphatidylinositol 3-kinase (PI3K)/Akt 신호전달체계를 저해시키는 약물에 의해서 완벽히 억제됨을 확인하였으나 ERK 신호전달체계를 저해시키는 약물에 의해서는 전혀 영향을 받지 않았다. 그리고 SKOV-3 세포에서 LPA에 의한 활성산소 형성이 시간에 따라 강하게 일어남을 확인하였다. 더욱이 LPA에 의한 활성산소 형성도 PI3K 또는 Akt의 저해제에 의해서 완벽히 억제됨을 확인하였으나 ERK 신호전달을 억제하였을 때는 거의 영향을 받지 않았다. SKOV-3 세포에서 LPA에 의해 생성된 활성산소는 diphenylene idonium (DPI, 10 μM), apocyanin (Apo, 10 μM)과 같은 NADPH oxidase 억제제를 전 처리하였을 때 활성산소가 형성되지 못함을 관찰하였다. 그러나 xanthine oxidase (allopurinol, Allo, 10 μM), cyclooxygenase (indomethacin, Indo, 10 μM), 또는 mitochondrial respiratory chain complex I (rotenone, Rot, 10 μM)를 억제하였을 때는 LPA에 의한 활성산소 형성에 영향을 주지 못함을 확인하였다. 마지막으로 활성산소 억제제인 N-acetylcysteine (NAC, 10 μM)에 의해서 LPA에 의한 암세포의 이동이 억제됨을 관찰하였다. 이와 더불어 LPA에 의한 SKOV-3 세포의 이동도 NADPH oxidase 억제에 의해 저해가 됨을 확인하였다. 이러한 연구결과로 보아 LPA에 의한 활성산소의 형성에는 3K/Akt/NADPH oxidase 신호전달체계가 중추적인 역할을 하며 이를 통해 암세포의 이동을 조절한다는 것을 알 수 있었다. Cell motility plays an essential role in many physiological responses, such as development, immune reaction, and angiogenesis. In the present study, we showed that lysophosphatidic acid (LPA) modulates cancer cell migration by regulation of generation of reactive oxygen species (ROS). Stimulation of SKOV-3 ovarian cancer cells with LPA strongly promoted migration. but this migration was completely blocked by pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Inhibition of the ERK pathway had no effect on migration. Stimulation of SKOV-3 ovarian cancer cells with LPA significantly induced the generation of ROS in a time-dependent manner. LPA-induced generation of ROS was significantly blocked by pharmacological inhibition of PI3K or Akt, but inhibition of the ERK signaling pathway had little effect. LPA-induced generation of ROS was blocked by pretreatment of SKOV-3 ovarian cancer cells with an NADPH oxidase inhibitor, whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I had no effect. Scavenging of ROS by N-acetylcysteine completely blocked LPA-induced migration of SKOV-3 ovarian cancer cells. Inhibition of NADPH oxidase blocked LPA-induced migration whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I did not affect LPA-induced migration of SKOV-3 ovarian cancer cells. Given these results, we suggest that LPA induces ROS generation through the PI3K/Akt/NADPH oxidase signaling axis, thereby regulating cancer cell migration.

전립선조직검사 적응증

구자윤(Ja Yoon Ku),전태경(Tae Kyung Jern),하홍구(Hong Koo Ha) 대한비뇨기종양학회 2014 대한비뇨기종양학회지 Vol.12 No.2

The prevalence of prostate cancer is stiffly increasing in Korea. In contrasts to the frequency of occurrence, there is no definite guideline for the cut off value of serum PSA. So, we reviewed the usefulness of serum PSA and recently reported guidelines in the prostate cancer detection. Nowadays, the cut off value of PSA continued to change, moreover, it is difficult to satisfied both sensitivity and specificity, at the same time. Also, the value of PSA relies on the assay method or laboratory. Various methods such as the percent of free PSA, PSA velocity and PSA doubling time have been used to enhance the detection rate during prostate biopsy. However, these methods did not make certainty in deciding whether performing the prostate biopsy. To complement the uncertainty of PSA and its derivatives, the new ways such as proPSA, PCA3 and gene fusion have been recently documented. Currently, the clearly indication of prostate biopsy is placed in controversy. Therefore, in the future, new methods to overcome non-specificity of PSA should be considered.

Risk Factors for pT3a Prostate Cancer in the Patients With cT1-2 on Preoperative Multiparametric Magnetic Resonance Imaging

Kyung Hwan Kim(김경환),Ja Yoon Ku(구자윤),Won Young Park(박원영),Seung Baek Hong(홍승백),Suk Kim(김석),Hong Koo Ha(하홍구) 대한비뇨기종양학회 2020 대한비뇨기종양학회지 Vol.18 No.2

Purpose: Our study aimed to evaluate the predictive value of multiparametric magnetic resonance imaging (mpMRI) to assess the capsular extension of prostate cancer. Risk factors for extraprostatic invasion or microscopic invasion of bladder neck (pT3a stage) in the cases showing localized disease findings on MRI scan were also identified. Materials and Methods: We identified 198 patients who underwent robot-assisted or conventional laparoscopic radical prostatectomy in our institute between June, 2016 and May, 2018. Altogether, 170 patients with preoperational mpMRI scans and complete pathologic data were included. Positive and negative predictive values of mpMRI to detect capsular extension were estimated. Chi-square test was performed for ratio variables. Logistic regression analysis was performed to identify capsular invasion risk factors. Results: Median age and prostate-specific antigen level were 68 years and 7.5 ng/mL, respectively. Based on findings, 16 patients (9.4%) were identified as cT3a stage (unilateral or bilateral extraprostatic extension), whereas 37 patients (21.8%) as pT3a stage. Positive and negative predictive values of mpMRI to detect capsular extension were 75.0% and 73.9%, respectively. In the logistic regression analysis, positive biopsy core rate was the significant predictor for pT3a disease in the patients with negative capsular invasion findings on mpMRI (p<0.001). According to receiver-operating characteristic curve (area under the curve=0.691, p=0.001), the positive biopsy core rate of 0.275 was the best threshold. Conclusions: Multiparametric MRI is an appropriate test to predict pT3a disease preoperatively. The patients with positive core rate over 0.275 may have pT3a diseases despite negative image findings.

전이성 전립선암 환자에서 항남성 호르몬 요법의 예후 인자 비교

김정만,이창렬,하홍구,이완,정문기 부산대학교 병원 암연구소 2006 부산대병원학술지 Vol.- No.20

Purpose: The prognostic factors in patients with metastatic prostate cancer after androgen deprivation treatment was assessed retrospectively. Subject and Methods: Seventy patients with metastatic prostatic cancer treated with androgen deprivation therapy were included in this study. Variety of possible prognostic factors, such as age, pretreatment serum prostate specific antigen (PSA), Gleason score, value of nadir serum PSA, duration to nadir serum PSA and treatment modality were analyzed. Results: Median age of patients was 70.5 (56-90) years and 16 patients were expired, who's median survival time was 27.2 (6-97) months and median survival time of patients who are alive was 27.6 (3-82) months. Median survival time of pretreatment serum PSA level of 0-9.99 ng/ml, 10-99.99 ng/ml, 100-499.99 ng/ml and >500 ng/ml was 42.0, 23, 19 and 15 months, repectively (p=0.019). Median survival time of nadir serum PSA of 0-0.2 ng/ml, 0.21-4 ng/ml and >4 ng/ml was 22.5, 19.5 and 16 months, repectively (p<0.0001). Median survival time of monotherapy and combination therapy was 23 and 19 months, respectively (p=0.035). But age, gleason score and duration to nadir serum PSA did not relate significantly with survival. Conclusion: The results of present study suggest that pretreatment serum PSA, the value of nadir serum PSA and treatment modality are significant prognostic indicators for survival in patients with metastatic prostate cancer treated with androgen deprivation therapy.

Rebamipide의 사람 정액내 항산화효과

박남철,심상보,엄박천,차창석,하홍구 大韓泌尿器科學會 2002 Korean Journal of Urology Vol.43 No.4