2020 Korean guidelines for the management of metastatic prostate cancer

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.

A study on research trends for gestational diabetes mellitus and breastfeeding: Focusing on text network analysis and topic modeling / 한국간호교육학회지

Purpose@#The aim of this study was to identify core keywords and topic groups in the ‘Gestational diabetes mellitus (GDM) and Breastfeeding’ field of research for better understanding research trends in the past 20 years. @*Methods@#This was a text-mining and topic modeling study composed of four steps: 1) collecting abstracts, 2) extracting and cleaning semantic morphemes, 3) building a co-occurrence matrix, and 4) analyzing network features and clustering topic groups. @*Results@#A total of 635 papers published between 2001 and 2020 were found in databases (Web of Science, CINAHL, RISS, DBPIA, RISS, KISS). Among them, 3,639 words extracted from 366 articles selected according to the conditions were analyzed by text network analysis and topic modeling. The most important keywords were 'exposure', ‘fetus’, ‘hypoglycemia’, 'prevention' and 'program'. Six topic groups were identified through topic modeling. The main topics of the study were ‘cardiovascular disease' and 'obesity'. Through the topic modeling analysis, six themes were derived: ‘cardiovascular disease’, ‘obesity’, ‘complication prevention strategy’, ‘support of breastfeeding’, ‘educational program’ and ‘management of GDM’. @*Conclusion@#This study showed that over the past 20 years many studies have been conducted on complications such as cardiovascular diseases and obesity related to gestational diabetes and breastfeeding. In order to prevent complications of gestational diabetes and promote breastfeeding, various nursing interventions, including gestational diabetes management and educational programs for GDM pregnancies, should be developed in nursing fields.

2020 Korean guidelines for the management of metastatic prostate cancer

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.

A study on research trends for gestational diabetes mellitus and breastfeeding: Focusing on text network analysis and topic modeling / 한국간호교육학회지

Purpose@#The aim of this study was to identify core keywords and topic groups in the ‘Gestational diabetes mellitus (GDM) and Breastfeeding’ field of research for better understanding research trends in the past 20 years. @*Methods@#This was a text-mining and topic modeling study composed of four steps: 1) collecting abstracts, 2) extracting and cleaning semantic morphemes, 3) building a co-occurrence matrix, and 4) analyzing network features and clustering topic groups. @*Results@#A total of 635 papers published between 2001 and 2020 were found in databases (Web of Science, CINAHL, RISS, DBPIA, RISS, KISS). Among them, 3,639 words extracted from 366 articles selected according to the conditions were analyzed by text network analysis and topic modeling. The most important keywords were 'exposure', ‘fetus’, ‘hypoglycemia’, 'prevention' and 'program'. Six topic groups were identified through topic modeling. The main topics of the study were ‘cardiovascular disease' and 'obesity'. Through the topic modeling analysis, six themes were derived: ‘cardiovascular disease’, ‘obesity’, ‘complication prevention strategy’, ‘support of breastfeeding’, ‘educational program’ and ‘management of GDM’. @*Conclusion@#This study showed that over the past 20 years many studies have been conducted on complications such as cardiovascular diseases and obesity related to gestational diabetes and breastfeeding. In order to prevent complications of gestational diabetes and promote breastfeeding, various nursing interventions, including gestational diabetes management and educational programs for GDM pregnancies, should be developed in nursing fields.

Erratum: Correction of the Text in the Article “Table”: Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study

While recently extending that research, however, the authors discovered that 236 members of the general population were mistakenly to be duplicated by the investigating agency (Word Research) and 1,241 were reported rather than 1,005. The authors present corrections and discuss the relevant data. The authors wish to apologize to the publisher and readers of Journal of Korean Medical Science for these errors.

Erratum: Correction of the Text in the Article “Table”: Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study

While recently extending that research, however, the authors discovered that 236 members of the general population were mistakenly to be duplicated by the investigating agency (Word Research) and 1,241 were reported rather than 1,005. The authors present corrections and discuss the relevant data. The authors wish to apologize to the publisher and readers of Journal of Korean Medical Science for these errors.

Erratum: Correction of the Text in the Article “Table”: Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study

While recently extending that research, however, the authors discovered that 236 members of the general population were mistakenly to be duplicated by the investigating agency (Word Research) and 1,241 were reported rather than 1,005. The authors present corrections and discuss the relevant data. The authors wish to apologize to the publisher and readers of Journal of Korean Medical Science for these errors.

Erratum: Correction of Ethics Statement: Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study

The approval number of Institutional Review Board (IRB) was wrong in the article.

Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study

BACKGROUND: It is difficult to decide whether to inform the child of the incurable illness. We investigated attitudes of the general population and physicians toward prognosis disclosure to children and associated factors in Korea. METHODS: Physicians working in one of 13 university hospitals or the National Cancer Center and members of the general public responded to the questionnaire. The questionnaire consisted of the age appropriate for informing children about the prognosis and the reason why children should not be informed. This survey was conducted as part of research to identify perceptions of physicians and general public on the end-of-life care in Korea. RESULTS: A total of 928 physicians and 1,241 members of the general public in Korea completed the questionnaire. Whereas 92.7% of physicians said that children should be informed of their incurable illness, only 50.7% of the general population agreed. Physicians were also more likely to think that younger children should know about their poor prognosis compared with the general population. Physicians who opposed incurable illness disclosure suggested that children might not understand the situation, whereas the general public was primarily concerned that disclosure would exacerbate the disease. Physicians who were women or religious were more likely to want to inform children of their poor prognosis. In the general population, gender, education, comorbidity, and caregiver experience were related to attitude toward poor prognosis disclosure to children. CONCLUSION: Our findings indicate that physicians and the general public in Korea differ in their perceptions about informing children of poor prognosis.

Korean Treatment Guidelines for Metastatic Prostate Cancer Developed by the Korean Association for Clinical Oncology / 대한내과학회지

The management of advanced prostate cancer has evolved rapidly. Androgen deprivation therapy, via surgical or medical castration, is the first-line therapy for hormone-naïve metastatic prostate cancer. For approximately a decade, docetaxel-based chemotherapy was the only approved agent to show a survival benefit for castration-resistant prostate cancer. However, over the last 5 years, significant advances in the field have led to the approval of several new agents with different mechanisms of action, such as the new androgen pathway inhibitors abiraterone and enzalutamide, a new cytotoxic agent, cabazitaxel, and new bone-seeking agents such as radium-223, which have all been associated with improved quality of life and pain palliation and an increase in survival. However, there has been no Korean treatment guideline for metastatic prostate cancer which is developed based on thorough search for relevant articles, including recently developed agents, and adequate review and assessment of evidences, and thus, a guideline adequate for domestic circumstance is eagerly needed. Experts from the Genitourinary Oncology Committee of the Korea Cancer Study Group developed clinical recommendations for the treatment of metastatic prostate cancer based on 19 key questions. The Korean Association for Clinical Oncology, the Korean Prostate Society, the Korean Urological Oncology Society, and the Korean Society of Pathologists reviewed and endorsed the guidelines. These are the first Korean treatment guidelines developed specifically for metastatic prostate cancer.

Prediction of survival by applying current prognostic models in diffuse large B-cell lymphoma treated with R-CHOP followed by autologous transplantation

BACKGROUND: Among the currently available prognostic models for diffuse large B-cell lymphoma (DLBCL), we investigated to determine which is most adoptable for DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) followed by upfront autologous stem cell transplantation (auto-SCT). METHODS: We retrospectively evaluated survival differences among risk groups based on the International Prognostic Index (IPI), the age-adjusted IPI (aaIPI), the revised IPI (R-IPI), and the National Comprehensive Cancer Network IPI (NCCN-IPI) at diagnosis in 63 CD20-positive DLBCL patients treated with R-CHOP followed by upfront auto-SCT. RESULTS: At the time of auto-SCT, 74.6% and 25.4% of patients had achieved complete remission and partial remission after R-CHOP, respectively. As a whole, the 5-year overall (OS) and progression-free survival (PFS) rates were 78.8% and 74.2%, respectively. The 5-year OS and PFS rates according to the IPI, aaIPI, R-IPI, and NCCN-IPI did not significantly differ among the risk groups for each prognostic model (P-values for OS: 0.255, 0.337, 0.881, and 0.803, respectively; P-values for PFS: 0.177, 0.904, 0.295, and 0.609, respectively). CONCLUSION: There was no ideal prognostic model among those currently available for CD20-positive DLBCL patients treated with R-CHOP followed by upfront auto-SCT.

Ginsenoside Rg1 and 20(S)-Rg3 Induce IgA Production by Mouse B Cells

Ginsenosides are the major components of ginseng, which is known to modulate blood pressure, metabolism, and immune function, and has been used to treat various diseases. It has been reported that ginseng and several ginsenosides have immunoregulatory effects on the innate and T cell-mediated immune response. However, their effects on the humoral immune response have not been fully explored. The present study examined the direct effects of red ginseng extract (RGE) and ginsenosides on mouse B cell proliferation and on antibody production and the expression of germline transcripts (GLT) by mouse B cells in vitro. RGE slightly reduced B cell proliferation, but increased IgA production by LPS-stimulated B cells. Furthermore, ginsenoside Rg1 and 20(S)-Rg3 selectively induced IgA production and expression of GLTalpha transcripts by LPS-stimulated B cells. Collectively, these results suggest that ginsenoside Rg1 and 20(S)-Rg3 can drive the differentiation of B cells into IgA-producing cells through the selective induction of GLTalpha expression.

R-CHOP chemoimmunotherapy followed by autologous transplantation for the treatment of diffuse large B-cell lymphoma

BACKGROUND: We investigated factors that influence outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab combined with the CHOP regimen (R-CHOP) followed by upfront autologous stem cell transplantation (Auto-SCT). METHODS: We retrospectively evaluated survival differences between subgroups based on the age-adjusted International Prognostic Index (aaIPI) and revised-IPI (R-IPI) at diagnosis, disease status, and positron emission tomographic/computerized tomographic (PET/CT) status at transplantation in 51 CD20-positive DLBCL patients treated with R-CHOP followed by upfront Auto-SCT. RESULTS: Patients had either stage I/II bulky disease (5.9%) or stage III/IV disease (94.1%). The median patient age at diagnosis was 47 years (range, 22-66 years); 53.3% and 26.7% had high-intermediate and high risks according to aaIPI, respectively. At the time of Auto-SCT, 72.5% and 27.5% experienced complete (CR) and partial remission (PR) after R-CHOP, respectively. The median time from diagnosis to Auto-SCT was 7.27 months (range, 3.4-13.4 months). The 5-year overall (OS) and progression-free survival (PFS) were 77.3% and 72.4%, respectively. The 5-year OS and PFS rates according to aaIPI, R-IPI, and PET/CT status did not differ between the subgroups. More importantly, the 5-year OS and PFS rates of the patients who achieved PR at the time of Auto-SCT were not inferior to those of the patients who achieved CR (P=0.223 and 0.292, respectively). CONCLUSION: Survival was not influenced by the aaIPI and R-IPI at diagnosis, disease status, or PET/CT status at transplantation, suggesting that upfront Auto-SCT might overcome unfavorable outcomes attributed to PR after induction chemoimmunotherapy.

SUMO Proteins are not Involved in TGF-beta1-induced, Smad3/4-mediated Germline alpha Transcription, but PIASy Suppresses it in CH12F3-2A B Cells

TGF-beta induces IgA class switching by B cells. We previously reported that Smad3 and Smad4, pivotal TGF-beta signal-transducing transcription factors, mediate germline (GL) alpha transcription induced by TGF-beta1, resulting in IgA switching by mouse B cells. Post-translational sumoylation of Smad3 and Smad4 regulates TGF-beta-induced transcriptional activation in certain cell types. In the present study, we investigated the effect of sumoylation on TGF-beta1-induced, Smad3/4-mediated GLalpha transcription and IgA switching by mouse B cell line, CH12F3-2A. Overexpression of small ubiquitin-like modifier (SUMO)-1, SUMO-2 or SUMO-3 did not affect TGF-beta1-induced, Smad3/4-mediated GLalpha promoter activity, expression of endogenous GLalpha transcripts, surface IgA expression, and IgA production. Next, we tested the effect of the E3 ligase PIASy on TGF-beta1-induced, Smad3/4-mediated GLalpha promoter activity. We found that PIASy overexpression suppresses the GLalpha promoter activity in cooperation with histone deacetylase 1. Taken together, these results suggest that SUMO itself does not affect regulation of GLalpha transcription and IgA switching induced by TGF-beta1/Smad3/4, while PIASy acts as a repressor.

Dectin-1 Stimulation Selectively Reinforces LPS-driven IgG1 Production by Mouse B Cells

Dectin-1, which specifically recognizes beta-glucan of fungal cell walls, is a non-Toll-like receptor (TLR) pattern recognition receptor and a representative of C-type lectin receptors (CLRs). The importance of Dectin-1 in innate immune cells, such as dendritic cells and macrophages, has previously been well studied. However, the function of Dectin-1 in B cells is very poorly understood. To determine the role of Dectin-1 in B cell activation, we first investigated whether mouse B cells express Dectin-1 and then assessed the effect of Dectin-1 stimulation on B cell proliferation and antibody production. Mouse B cells express mRNAs encoding CLRs, including Dectin-1, and surface Dectin-1 was expressed in B cells of C57BL/6 rather than BALB/c strain. Dectin-1 agonists, heat-killed Candida albicans (HKCA) and heat-killed Saccharomyces cerevisiae (HKSC), alone induced B cell proliferation but not antibody production. Interestingly, HKSC, HKCA, and depleted zymosan (a selective Dectin-1 agonist) selectively enhanced LPS-driven IgG1 production. Taken together, these results suggest that, during fungal infection, beta-glucan-stimulated Dectin-1 may cooperate with TLR4 to specifically enhance IgG1 production by mouse B cells.

Kinetic Analysis of CpG-Induced Mouse B Cell Growth and Ig Production

Immune cells express toll-like receptors (TLRs) and respond to molecular patterns of various pathogens. CpG motif in bacterial DNA activates innate and acquired immune systems through binding to TLR9 of immune cells. Several studies reported that CpG can directly regulate B cell activation, differentiation, and Ig production. However, the role of CpG in B cell growth and Ig production is not fully understood. In this study, we analyzed the effect of CpG on the kinetics of mouse B cell viability, proliferation, and Igs production. Overall, CpG enhanced mouse B cell growth and production of Igs in a dose-dependent manner. Unlike LPS, 100 nM CpG (high dose) did not support TGF-beta1-induced IgA and IgG2b production. Moreover, 100 nM CpG treatment abrogated either LPS-induced IgM or LPS/TGF-beta1-induced IgA and IgG2b production, although B cell growth was enhanced by CpG under the same culture conditions. We subsequently found that 10 nM CpG (low dose) is sufficient for B cell growth. Again, 10 nM CpG did not support TGF-beta1-induced IgA production but, interestingly enough, supported RA-induced IgA production. Further, 10 nM CpG, unlike 100 nM, neither abrogated the LPS/TGF-beta1-nor the LPS/RA-induced IgA production. Taken together, these results suggest that dose of CpG is critical in B cell growth and Igs production and the optimal dose of CpG cooperates with LPS in B cell activation and differentiation toward Igs production.

The Effect of Tissue Plasminogen Activator on TGF-beta1 Pre-Treated Human Mesothelial Cell Line / 결핵및호흡기질환

BACKGROUND: In an effort to find alternative therapeutic agents to prevent excessive fibrosis as a sequela to complicated parapneumonic effusion or empyema, we examined the effect of tissue plasminogen activator (tPA) as a fibrinolytic agent combined with talc or transforming growth factor (TGF)-beta1 in a human pleural mesothelial cell line, MeT-5A. METHODS: MeT-5A cells were stimulated with various doses of talc, doxycycline or TGF-beta1 for 24 h and then were treated with tPA for an additional 24 h. Cell viability was measured by MTT assay. The production of interleukin (IL)-8 and vascular endothelial growth factor (VEGF) in the culture supernatants was measured by ELISA. Real-time PCR was carried out for measurement of type I collagen mRNA. RESULTS: MeT-5A cells treated with talc showed a dose-dependent increase in production of IL-8. Talc also increased production of type I collagen mRNA at low doses, but talc did not influence the induction of VEGF. Addition of tPA to talc-stimulated cells showed further increases in the production of IL-8, but tPA did not influence the production of VEGF or type I collagen mRNA. TGF-beta1 increased the production of both VEGF and collagen type I mRNA, both of which were effectively inhibited by additional tPA treatment in MeT-5A cells. CONCLUSION: TGF-beta1 is a potent inducer of collagen synthesis without induction of IL-8 in MeT-5A cells. Addition of tPA after TGF-beta1 stimulation inhibited further fibrosis by direct inhibition of collagen mRNA synthesis as well as by inhibition of VEGF production.

Production of TNF-alpha and IL-6 in Macrophages by Mycobacterial Protein Antigens

BACKGROUND: Mycobacterial antigens released as PIM, LM, LAM, lipoproteins and other cellular factors may contribute to macrophage and dendritic cell activation through pattern recognition receptors such as TLRs. In this study, we assessed cytokine production and ERK activation with stimulation of several major mycobacterial antigens. METHODS: Purified mycobacterial antigens (10, 22, 30, 38kappaDa) and recombinant antigens (6, 16, 19, 38kappaDa, Ag85A antigen) were studied. The production of cytokines (TNF-alpha, IL-12, IL-6) was measured by ELISA. The ERK activation was detected by western blotting. The expression of TLR2 or TLR4 was measured by flow cytometry. RESULTS: Among purified antigens only 30kappaDa antigen induced production of IL-6 or TNF-alpha in THP-1 macrophage cells. When THP-1 macrophage cells were treated with 30kappaDa antigen, phosphorylation of ERK was detected. ERK activation also occurred in TLR2 transfectant HEK293 cells with 30kappaDa antigen stimulation. CONCLUSION: 30kappaDa antigen is one of the major mycobacterial antigens inducing cytokine production and MAP kinases phosphorylation in macrophages.

Purification of Native Ag85 Complex, 38-kDa and MTB12 Protein Antigens from the Culture Filtrate of Mycobacterium tuberculosis

The purification of immunodominant native protein antigens from the culture filtrates of Mycobacterium tuberculosis is needed for the development of new vaccines and immunodiagnostic reagents against tuberculosis. In the present study, we conducted large scale purification of well-known secreted antigens, Ag85 complex, 38-kDa, and MTB12, from the culture filtrate proteins (CFPs) prepared from M. tuberculosis H37Rv grown as a surface pellicle on synthetic Sauton medium. The protein and antigen concentrations of culture filtrates were sufficiently increased after 6 week of culture. The MTB12 antigen was detected as early as 1 week of culture, and Ag85 complex and 38-kDa antigen were detected after 2 and 3 week of culture, respectively, by immunodiffusion with specific antiserum against 100-fold concentrated culture filtrates. For large-scale purification, the six-week-culture filtrates of M. tuberculosis H37Rv diluted 2.5-fold with 20 mM Tris-HCl, (P)H 8.3 were subjected to anion-exchange chromatography. The CFPs were eluted with 100 mM NaCl-20 mM Tris-HCl, pH 8.3 and concentrated by ultrafiltration. The concentrated CFPs were fractionated with ammonium sulfate, and followed by hydrophobic interaction chromatography and anion-exchange chromatography (FPLC). Eventually, 10 mg of Ag85 complex, 0.56 mg of 38-kDa, and 1.81 mg of MTB12 antigens were purified from 1 liter of the six-week-culture filtrates of M. tuberculosis H37Rv which contained 307.81 mg of protein of culture filtrate.

Induction of TNF-alpha, IL-12, IL-10, MCP-1 and IL-8 in Human Peripheral Blood Monocytes in Response to the Cell Wall-Associated Triton X-100 Soluble Protein (TSP) Antigens of Mycobacterium tuberculosis

Mycobacterium tuberculosis is a potent inducer of cytokine production by mononuclear phagocytes, which are an important cellular component in the first line immune defence. In this study, the cell wall-associated Triton X-100 soluble protein (TSP) antigens, TSP-H37Rv, TSP-H37Ra, TSP-K, and TSP-BCG, were isolated from M. tuberculosis H37Rv, M. tuberculosis H37Ra, M. tuberculosis K-strain, and M. bovis BCG, respectively. The monocytes were isolated from the peripheral blood mononuclear cells of healthy individuals and were co-cultured with each TSP antigens and the secretory proteins of M. tuberculosis (PPD and 30-kDa antigen) to measure the production of cytokines; tumor necrosis factor (TNF)-a, interleukin (IL)-12, IL-8 and monocyte chemotactic protein-1 (MCP-1). The TSP-H37Rv antigen- stimulated monocytes showed higher level of TNF-a and IL-12 production compared to those of other TSP antigens and PPD. Especially, IL-12 production in response to the TSP-H37Rv antigen was significantly elevated in comparison with that of PPD-stimulated monocytes (TSP-H37Rv, 255.5+/-256.9 pg/ml; PPD, 55.7+/-55.4 pg/ml). However, the 30-kDa antigen did not induce TNF-alpha expression and also showed the lowest level of cytokine and chemokine production by monocytes. MCP-1 and IL-8 production were similarly increased in response to all TSP antigens and the PPD antigen. The production of IL-12 by the TSP-H37Rv antigen stimulation was significantly increased in PPD reactors than that in the non-reactor group, while the levels of other cytokines stimulated with each TSP antigens, 30-kDa and PPD antigen were not significantly different between the tuberculin reactor and the non-reactor groups. These results suggest that the cell wall-associated TSP antigen isolated from M. tuberculosis H37Rv acts as a more potent IL-12 inducer than the PPD antigen in innate immune response and thus it could further activate the Th1-mediated immune responses effectively against M. tuberculosis infection.