Publications by authors named "Sun Mi Yoo"

14 Publications

  • Page 1 of 1

Trend in Prevalence of Smoking and Motivation to Quit among Korean Adult Male Cancer Survivors over the Last 8 Years: The Korea National Health and Nutrition Examination Survey V-VII (2010-2017).

Korean J Fam Med 2021 Jul 20;42(4):281-287. Epub 2021 Jul 20.

Department of Family Medicine, Inje University Haeundae Paik Hospital, Busan, Korea.

Background: This study aimed to investigate trends in the prevalence of current smokers and motivation to quit among Korean male cancer survivors.

Methods: Out of 20,012 men who participated in the Korea National Health and Nutrition Examination Survey V (2010-2012), VI (2013-2015), and VII (2016-2017), 742 cancer survivors were included. A cancer survivor was defined as a person who concurred to the item, "The cancer has been diagnosed by a doctor" in the health questionnaire. Smoking status was classified as current, former, and never smokers. Regarding motivation to quit smoking, we defined those who had a willingness to quit within 6 months as the willing group. Logistic regression analysis was conducted to examine trends in the prevalence of current smokers and the proportion of the willing group among current smokers.

Results: Overall, 3.7% of Korean men who participated in the study were cancer survivors. Current smokers constituted 19.5%, 19.1%, and 15.3% of cancer survivors in phases V, VI, and VII respectively which did not show significant changes (P for trend=0.33). However, the proportion of current smokers in the non-cancer group was significantly reduced to 46.6%, 41.2%, and 38.9% in phases V, VI, and VII, respectively (P for trend <0.001). The proportion of those with a motivation to quit smoking did not show a significant trend in the cancer survivors (P for trend=0.964) and non-cancer group (P for trend=0.884).

Conclusion: Prevalence of current smokers and motivation to quit in Korean male cancer survivors did not show significant trends.
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http://dx.doi.org/10.4082/kjfm.19.0134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321906PMC
July 2021

FBXW7-mediated stability regulation of signal transducer and activator of transcription 2 in melanoma formation.

Proc Natl Acad Sci U S A 2020 01 16;117(1):584-594. Epub 2019 Dec 16.

College of Pharmacy, The Catholic University of Korea, Bucheon-si, Gyeonggi-do 14662, Republic of Korea;

In this study, we provide critical evidence that STAT2 stability regulation plays an essential role in melanoma cell proliferation and colony growth. We found that the interaction of FBXW7 and STAT2 induced STAT2 destabilization via a ubiquitination-mediated proteasomal degradation pathway. Notably, GSK3β-mediated STAT2 phosphorylation facilitated STAT2-FBXW7 interactions via the DNA binding domain of STAT2 and domains 1, 2, 6, and 7 of FBXW7 WD40. Importantly, the inverse correlation between protein levels of STAT2 and FBXW7 were observed not only in human melanoma cells but also in a human skin cancer tissue array. The relationship between protein levels of STAT2 and FBXW7, cell proliferation, and colony growth were similarly observed in the melanoma cell lines SK-MEL-2, -5, and -28. Moreover, STAT2 knockdown in melanoma cells suppressed melanoma cell proliferation and colony formation. These data demonstrated that FBXW7-mediated STAT2 stability regulation plays an essential role in melanoma cell proliferation and cancer growth.
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http://dx.doi.org/10.1073/pnas.1909879116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955312PMC
January 2020

RSK2-Mediated ELK3 Activation Enhances Cell Transformation and Breast Cancer Cell Growth by Regulation of c-fos Promoter Activity.

Int J Mol Sci 2019 Apr 23;20(8). Epub 2019 Apr 23.

Integrated Research Institute of Pharmaceutical Sciences, BRL & BK21 Plus team, Pharmaceutical Biochemistry, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Korea.

Ribosomal S6 kinase 2 (RSK2), regulated by Ras/Raf/MEKs/ERKs, transmits upstream activation signals to downstream substrates including kinases and transcription and epigenetic factors. We observed that ELK members, including ELK1, 3, and 4, highly interacted with RSK2. We further observed that the RSK2-ELK3 interaction was mediated by N-terminal kinase and linker domains of RSK2, and the D and C domains of ELK3, resulting in the phosphorylation of ELK3. Importantly, RSK2-mediated ELK3 enhanced promoter activity. Notably, chemical inhibition of RSK2 signaling using kaempferol (a RSK2 inhibitor) or U0126 (a selective MEK inhibitor) suppressed EGF-induced promoter activity. Moreover, functional deletion of RSK2 by knockdown or knockout showed that RSK2 deficiency suppressed EGF-induced promoter activity, resulting in inhibition of AP-1 transactivation activity and Ras-mediated foci formation in NIH3T3 cells. Immunocytofluorescence assay demonstrated that RSK2 deficiency reduced ELK3 localization in the nucleus. In MDA-MB-231 breast cancer cells, knockdown of RSK2 or ELK3 suppressed cell proliferation with accumulation at the G1 cell cycle phase, resulting in inhibition of foci formation and anchorage-independent cancer colony growth in soft agar. Taken together, these results indicate that a novel RSK2/ELK3 signaling axis, by enhancing c-Fos-mediated AP-1 transactivation activity, has an essential role in cancer cell proliferation and colony growth.
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http://dx.doi.org/10.3390/ijms20081994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515335PMC
April 2019

Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis.

Eur Urol 2020 01 13;77(1):3-10. Epub 2019 Apr 13.

Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.

Background: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases.

Objective: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT).

Design, Setting, And Participants: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT).

Outcome Measurements And Statistical Analysis: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment.

Results And Limitations: A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS).

Conclusions: WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted.

Patient Summary: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.
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http://dx.doi.org/10.1016/j.eururo.2019.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521828PMC
January 2020

Epimagnolin targeting on an active pocket of mammalian target of rapamycin suppressed cell transformation and colony growth of lung cancer cells.

Mol Carcinog 2019 07 18;58(7):1221-1233. Epub 2019 Mar 18.

Pharmaceutical Biochemistry, Basic Research Laboratory & BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, Republic of Korea.

Mammalian target of rapamycin (mTOR) has a pivotal role in carcinogenesis and cancer cell proliferation in diverse human cancers. In this study, we observed that epimagnolin, a natural compound abundantly found in Shin-Yi, suppressed cell proliferation by inhibition of epidermal growth factor (EGF)-induced G1/S cell-cycle phase transition in JB6 Cl41 cells. Interestingly, epimagnolin suppressed EGF-induced Akt phosphorylation strongly at Ser473 and weakly at Thr308 without alteration of phosphorylation of MAPK/ERK kinases (MEKs), extracellular signal-regulated kinase (ERKs), and RSK1, resulting in abrogation of the phosphorylation of GSK3β at Ser9 and p70S6K at Thr389. Moreover, we found that epimagnolin suppressed c-Jun phosphorylation at Ser63/73, resulting in the inhibition of activator protein 1 (AP-1) transactivation activity. Computational docking indicated that epimagnolin targeted an active pocket of the mTOR kinase domain by forming three hydrogen bonds and three hydrophobic interactions. The prediction was confirmed by using in vitro kinase and adenosine triphosphate-bead competition assays. The inhibition of mTOR kinase activity resulted in the suppression of anchorage-independent cell transformation. Importantly, epimagnolin efficiently suppressed cell proliferation and anchorage-independent colony growth of H1650 rather than H460 lung cancer cells with dependency of total and phosphorylated protein levels of mTOR and Akt. Inhibitory signaling of epimagnolin on cell proliferation of lung cancer cells was observed mainly in mTOR-Akt-p70S6K and mTOR-Akt-GSK3β-AP-1, which was similar to that shown in JB6 Cl41 cells. Taken together, our results indicate that epimagnolin potentiates as chemopreventive or therapeutic agents by direct active pocket targeting of mTOR kinase, resulting in sensitizing cancer cells harboring enhanced phosphorylation of the mTORC2-Akt-p70S6k signaling pathway.
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http://dx.doi.org/10.1002/mc.23005DOI Listing
July 2019

Magnolin targeting of ERK1/2 inhibits cell proliferation and colony growth by induction of cellular senescence in ovarian cancer cells.

Mol Carcinog 2019 01 21;58(1):88-101. Epub 2018 Sep 21.

Integrated Research Institute of Pharmaceutical Sciences, BK21 PLUS Team & BRL, College of Pharmacy, The Catholic University of Korea, Wonmi-gu, Bucheon-si, Gyeonggi-do, Korea.

Ras/Raf/MEKs/ERKs and PI3 K/Akt/mTOR signaling pathways have key roles in cancer development and growth processes, as well as in cancer malignance and chemoresistance. In this study, we screened the therapeutic potential of magnolin using 15 human cancer cell lines and combined magnolin sensitivity with the CCLE mutaome analysis for relevant mutation information. The results showed that magnolin efficacy on cell proliferation inhibition were lower in TOV-112D ovarian cancer cells than that in SKOV3 cells by G1 and G2/M cell cycle phase accumulation. Notably, magnolin suppressed colony growth of TOV-112D cells in soft agar, whereas colony growth of SKOV3 cells in soft agar was not affected by magnolin treatment. Interestingly, phospho-protein profiles in the MAPK and PI3 K signaling pathways indicated that SKOV3 cells showed marked increase of Akt phosphorylation at Thr308 and Ser473 and very weak ERK1/2 phosphorylation levels by EGF stimulation. The phospho-protein profiles in TOV-112D cells were the opposite of those of SKOV3 cells. Importantly, magnolin treatment suppressed phosphorylation of RSKs in TOV-112D, but not in SKOV3 cells. Moreover, magnolin increased SA-β-galactosidase-positive cells in a dose-dependent manner in TOV-112D cells, but not in SKOV3 cells. Notably, oral administration of Shin-Yi fraction 1, which contained magnolin approximately 53%, suppressed TOV-112D cell growth in athymic nude mice by induction of p16 and p27 . Taken together, targeting of ERK1 and ERK2 is suitable for the treatment of ovarian cancer cells that do not harbor the constitutive active P13 K mutation and the loss-of-function mutations of the p16 and/or p53 tumor suppressor proteins.
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http://dx.doi.org/10.1002/mc.22909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585859PMC
January 2019

Relationship between Age at Menarche and Metabolic Syndrome in Premenopausal Women: Korea National Health and Nutrition Examination Survey 2013-2014.

Korean J Fam Med 2018 Sep 30;39(5):300-306. Epub 2018 Jul 30.

Department of Family Medicine, Inje University Haeundae Paik Hospital, Busan, Korea.

Background: Early menarche may be associated with increased risk of cardiovascular disease. The aim of this study was to evaluate the relationship between age at menarche and metabolic syndrome (MetS) in Korean premenopausal women.

Methods: We used nationally representative data from the Korea National Health and Nutrition Examination Survey from 2013 to 2014, and 3,023 premenopausal women aged 20-55 years were our subjects. We defined early menarche as age at first menstrual period less than 12 years. Multivariable logistic regression analysis was used to evaluate the relationship between age at menarche and MetS after adjusting for current age, and socioeconomic, lifestyle, and reproductive variables.

Results: MetS was much more common in women aged 40-55 years than in women aged 20-39 years (4.1% vs. 15.1%). Compared with women who experienced menarche at age 12-15 years, the risk of MetS in the early menarche group was not higher in either age group, after adjusting for current age, and socioeconomic, lifestyle, and reproductive variables (odds ratio [OR], 1.767; 95% confidence interval [CI], 0.718-4.351 in those aged 20-39 years; OR, 1.780; 95% CI, 0.775-4.085 in those aged 40-55 years). The risk of MetS in women with menarche at age ≥16 years was not higher than in women with menarche at age 12-15 years.

Conclusion: Early or late menarche was not associated with an increased risk of MetS in premenopausal Korean women. Even before menopause, current age has a major influence on the development of MetS.
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http://dx.doi.org/10.4082/kjfm.17.0022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166116PMC
September 2018

Relationship between Dry Eye Syndrome and Frequency of Coffee Consumption in Korean Adults: Korea National Health and Nutrition Examination Survey V, 2010-2012.

Korean J Fam Med 2018 Sep 27;39(5):290-294. Epub 2018 Jul 27.

Department of Family Medicine, Inje University Haeundae Paik Hospital, Busan, Korea.

Background: Dry eye syndrome is a common health problem in the adult population. Many risk factors including age, sex, prior eye surgery, various chronic diseases, and lifestyle factors can affect its development. We have evaluated the risk of dry eye syndrome based on the frequency of coffee consumption among Korean adult population.

Methods: A total of 9,752 adults with age 19 years and older were randomly selected between 2010 and 2012. They have all participated in the National Health and Nutrition Examination Survey V of Korea. Dry eye syndrome was being diagnosed by the physicians at some points in the participant's lifetime. The average daily coffee intake was divided into the following: less than 1 cup, 1 to 2 cups, and 3 cups or more. Various physio-environmental factors and medical conditions were used as correction variables to assess the risk of dry eye syndrome in relation to the frequency of coffee consumption.

Results: The prevalence of dry eye syndrome decreased to 9.2%, 8.8%, and 6.3% as coffee consumption increased from less than 1 cup to 1-2 cups and more than 3 cups, respectively. However, there was no significant relationship between the frequency of coffee consumption and the risk of dry eye syndrome after adjusting various risk factors.

Conclusion: There is no relationship between the frequency of coffee consumption and risk of dry eye syndrome.
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http://dx.doi.org/10.4082/kjfm.17.0047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166118PMC
September 2018

Clinical Outcomes for Patients With Gleason Score 10 Prostate Adenocarcinoma: Results From a Multi-institutional Consortium Study.

Int J Radiat Oncol Biol Phys 2018 07 5;101(4):883-888. Epub 2018 Apr 5.

Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, California.

Purpose: Gleason score (GS) 10 disease is the most aggressive form of clinically localized prostate adenocarcinoma (PCa). The long-term clinical outcomes and overall prognosis of patients presenting with GS 10 PCa are largely unknown because of its rarity.

Methods And Materials: The study included 112 patients with biopsy-determined GS 10 PCa who received treatment with radical prostatectomy (RP, n = 26), external beam radiation therapy (EBRT, n = 48), or EBRT with a brachytherapy boost (EBRT-BT, n = 38) between 2000 and 2013. Propensity scores were included as covariates for comparative analysis. Overall survival, prostate cancer-specific survival, and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method with inverse probability of treatment weighting to control for confounding.

Results: The median follow-up period was 4.9 years overall (3.9 years for RP, 4.8 years for EBRT, and 5.7 years for EBRT-BT). Significantly more EBRT patients than EBRT-BT patients received upfront androgen deprivation therapy (98% vs 79%, P < .01 by χ test), though the durations were similar (median, 24 months vs 22.5 months). Of the RP patients, 34% received postoperative EBRT, and 35% received neoadjuvant systemic therapy. The propensity score-adjusted 5-year overall survival rate was 80% for the RP group, 73% for the EBRT group, and 83% for the EBRT-BT group. The corresponding adjusted 5-year prostate cancer-specific survival rates were 87%, 75%, and 94%, respectively. The EBRT-BT group trended toward superior DMFS when compared with the RP group (hazard ratio, 0.3; 95% confidence interval 0.1-1.06; P = .06) and had superior DMFS when compared with the EBRT group (hazard ratio, 0.4; 95% confidence interval 0.1-0.99; P = .048).

Conclusions: To our knowledge, this is the largest series ever reported on the clinical outcomes of patients with biopsy-determined GS 10 PCa. These data provide useful prognostic benchmark information for physicians and patients. Aggressive therapy with curative intent is warranted, as >50% of patients remain free of systemic disease 5 years after treatment.
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http://dx.doi.org/10.1016/j.ijrobp.2018.03.060DOI Listing
July 2018

Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis.

Cell Death Dis 2018 03 14;9(3):401. Epub 2018 Mar 14.

Integrated Research Institute of Pharmaceutical Sciences & BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Republic of Korea.

Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis. Moreover, a molecular docking study revealed that kaempferol inhibited FGFR3 activity by binding to the active pocket of the FGFR3 kinase domain. Kaempferol forms hydrogen bonds with the FGFR3 backbone oxygen of Glu555 and Ala558 and the side chain of Lys508. Notably, the inhibition of bFGF-FGFR3-RSK2 signaling by kaempferol suppresses the proliferation and migration of RA FLSs and the release of activated T-cell-mediated inflammatory cytokines, such as IL-17, IL-21, and TNF-α. We further found that activated phospho-FGFR3 and -RSK2 were more highly observed in RA than in OA synovium. The hyperplastic lining and sublining lymphoid aggregate layers of RA synovium showed p-RSK2-expressing CD68 macrophages with high frequency, while pRSK2-expressing CD4 T-cells was observed at a lower frequency. Notably, kaempferol administration in collagen-induced arthritis mice relieved the frequency and severity of arthritis. Kaempferol reduced osteoclast differentiation in vitro and in vivo relative to the controls and was associated with the inhibition of osteoclast markers, such as tartrate-resistant acid phosphatase, integrin β3, and MMP9. Conclusively, our data suggest that bFGF-induced FGFR3-RSK2 signaling may play a critical role during the initiation and progression of RA in terms of FLS proliferation and enhanced osteoclastogenesis, and that kaempferol may be effective as a new treatment for RA.
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http://dx.doi.org/10.1038/s41419-018-0433-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851988PMC
March 2018

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer.

JAMA 2018 03;319(9):896-905

Department of Urology, University of California, Los Angeles.

Importance: The optimal treatment for Gleason score 9-10 prostate cancer is unknown.

Objective: To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment.

Design, Setting, And Participants: Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013.

Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy.

Main Outcomes And Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes.

Results: Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]).

Conclusions And Relevance: Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.
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http://dx.doi.org/10.1001/jama.2018.0587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885899PMC
March 2018

Gaps in Radiation Therapy Awareness: Results From an Educational Multi-institutional Survey of US Internal Medicine Residents.

Int J Radiat Oncol Biol Phys 2017 08 29;98(5):1153-1161. Epub 2017 Mar 29.

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California. Electronic address:

Purpose: Internists and primary care providers play a growing role in cancer care. We therefore evaluated the awareness of radiation therapy in general and specifically the clinical utility of stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) among current US internal medicine residents.

Methods And Materials: A web-based institutional review board-approved multi-institutional survey was distributed to US internal medicine residency programs. The survey evaluated trainee demographic characteristics, baseline radiation oncology awareness, knowledge of the role of SBRT for early-stage NSCLC, and whether the survey successfully improved awareness.

Results: Thirty US internal medicine programs participated, with an overall participant response rate of 46% (1177 of 2551). Of the trainees, 93% (n=1076) reported no radiation oncology education in their residency, 39% (n=452) reported confidence in knowing when to consult radiation oncology in an oncologic emergency, and 26% (n=293) reported confidence in knowing when to consult radiation oncology in the setting of a newly diagnosed cancer. Of the participants, 76% (n=850) correctly identified that surgical resection is the standard treatment in operable early-stage NSCLC, but only 50% (n=559) of participants would recommend SBRT to a medically inoperable patient, followed by 31% of participants (n=347) who were unsure of the most appropriate treatment, and 10% (n=117) who recommended waiting to offer palliative therapy. Ninety percent of participants (n=1029) agreed that they would benefit from further training on when to consult radiation oncology. Overall, 96% (n=1072) indicated that the survey increased their knowledge and awareness of the role of SBRT.

Conclusions: The majority of participating trainees received no education in radiation oncology in their residency, reported a lack of confidence regarding when to consult radiation oncology, and overwhelmingly agreed that they would benefit from further training. These findings should serve as a call to increase the educational collaboration between internal medicine and radiation oncology departments to ensure optimal cancer care.
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http://dx.doi.org/10.1016/j.ijrobp.2017.03.028DOI Listing
August 2017

Molecular Targeting of ERKs/RSK2 Signaling Axis in Cancer Prevention.

J Cancer Prev 2015 Sep;20(3):165-71

College of Pharmacy, The Catholic University of Korea, Bucheon, Korea.

RSK2 is a downstream signaling protein of ERK1 and ERK2 and plays a key role in physiological homeostasis. For this reason, RSK2 is a highly conserved protein among the p90RSK family members. In its location in the signaling pathway, RSK2 is a kinase just upstream of transcription and epigenetic factors, and a few kinases involved in cell cycle regulation and protein synthesis. Moreover, activation of RSK2 by growth factors is directly involved in cell proliferation, anchorage-independent cell transformation and cancer development. Direct evidences regarding the etiological roles of RSK2 in cancer development in humans have been published by our research group illustrating that elevated total- and phospho-RSK2 protein levels mediated by ERK1 and ERK2 are higher in skin cancer tissues compared to normal skin tissues. Notably, it has been shown that RSK2 ectopic expression in JB6 Cl41 cells induces cell proliferation and anchorage- independent cell transformation. Importantly, knockdown of RSK2 suppresses Ras-mediated foci formation and anchorage-independent colony growth of cancer cells. Kaempferol is a one of the natural compounds showing selectivity in inhibiting RSK2 activity in epidermal growth factor-induced G1/S cell cycle transition and cell transformation. Thus, ERKs/RSK2 signaling axis is an important target signaling molecule in chemoprevention.
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http://dx.doi.org/10.15430/JCP.2015.20.3.165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597804PMC
September 2015

Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway.

BMC Cancer 2015 Aug 8;15:576. Epub 2015 Aug 8.

College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Republic of Korea.

Background: Magnolin is a natural compound abundantly found in Magnolia flos, which has been traditionally used in oriental medicine to treat headaches, nasal congestion and anti-inflammatory reactions. Our recent results have demonstrated that magnolin targets the active pockets of ERK1 and ERK2, which are important signaling molecules in cancer cell metastasis. The aim of this study is to evaluate the effects of magnolin on cell migration and to further explore the molecular mechanisms involved.

Methods: Magnolin-mediated signaling inhibition was confirmed by Western blotting using RSK2(+/+) and RSK2(-/-) MEFs, A549 and NCI-H1975 lung cancer cells, and by NF-κB and Cox-2 promoter luciferase reporter assays. Inhibition of cell migration by magnolin was examined by wound healing and/or Boyden Chamber assays using JB6 Cl41 and A549 human lung cancer cells. The molecular mechanisms involved in cell migration and epithelial-to-mesenchymal transition were determined by zymography, Western blotting, real-time PCR and immunocytofluorescence.

Results: Magnolin inhibited NF-κB transactivation activity by suppressing the ERKs/RSK2 signaling pathway. Moreover, magnolin abrogated the increase in EGF-induced COX-2 protein levels and wound healing. In human lung cancer cells such as A549 and NCI-H1975, which harbor constitutive active Ras and EGFR mutants, respectively, magnolin suppressed wound healing and cell invasion as seen by a Boyden chamber assay. In addition, it was observed that magnolin inhibited MMP-2 and -9 gene expression and activity. The knockdown or knockout of RSK2 in A549 lung cancer cells or MEFs revealed that magnolin targeting ERKs/RSK2 signaling suppressed epithelial-to-mesenchymal transition by modulating EMT marker proteins such as N-cadherin, E-cadherin, Snail, Vimentin and MMPs.

Conclusions: These results demonstrate that magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway.
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http://dx.doi.org/10.1186/s12885-015-1580-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529708PMC
August 2015
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