Prognostic implications of tumor-infiltrating macrophages, M2 macrophages, regulatory T-cells, and indoleamine 2,3-dioxygenase-positive cells in primary diffuse large B-cell lymphoma of the central nervous system

Nam, Soo Jeong,Kim, Sehui,Kwon, Dohee,Kim, Hannah,Kim, Soyeon,Lee, Eunyoung,Kim, Tae Min,Heo, Dae Seog,Park, Sung Hye,Lim, Megan S.,Kim, Chul Woo,Jeon, Yoon Kyung TaylorFrancis 2018 Oncoimmunology Vol.7 No.7

<P><B>ABSTRACT</B></P><P>Primary diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) is an aggressive disease with a poor prognosis. The status of the tumor immune microenvironment in CNS-DLBCL remains unclear. We investigated the prognostic implications of tumor-associated macrophages (TAMs), regulatory T-cells (Tregs), and indoleamine 2,3-dioxygenase (IDO)<SUP>+</SUP> cells in primary CNS-DLBCL (n = 114) by immunohistochemical analysis. The numbers of tumor-infiltrating immune cells, including CD68<SUP>+</SUP> TAMs, CD163<SUP>+</SUP> or CD204<SUP>+</SUP> M2 macrophages, FOXP3<SUP>+</SUP> Tregs, and IDO<SUP>+</SUP> cells were all significantly lower in CNS-DLBCL versus systemic DLBCL (n = 165; all P < 0.001), but with little difference in the ratio of CD163<SUP>+</SUP>/CD68<SUP>+</SUP> or CD204<SUP>+</SUP>/CD68<SUP>+</SUP> cells. An increase in CD68<SUP>+</SUP> cell numbers was significantly associated with prolonged progression-free survival (PFS) and overall survival in patients with CNS-DLBCL (P = 0.004 and 0.021, respectively). In contrast, an increase in CD204<SUP>+</SUP> cell numbers or a higher ratio of CD204<SUP>+</SUP>/CD68<SUP>+</SUP> cells was related to a shorter PFS (P = 0.020 and 0.063, respectively). An increase in IDO<SUP>+</SUP> cell numbers was associated with a significantly longer PFS (P = 0.019). In combination, the status of low IDO<SUP>+</SUP> cell numbers combined with low CD68<SUP>+</SUP> cell numbers, high CD204<SUP>+</SUP> cell numbers, or a high CD204<SUP>+</SUP>/CD68<SUP>+</SUP> cell ratio all predicted poor PFS in multivariate analyses. This study showed that an increase in CD204<SUP>+</SUP> cell numbers, suggestive of M2 macrophages, was associated with poor clinical outcome in CNS-DLBCL, whereas increased CD68<SUP>+</SUP> or IDO<SUP>+</SUP> cell numbers were related to a favorable prognosis. The analysis of tumor-infiltrating immune cells could help in predicting the prognosis of CNS-DLBCL patients and determining therapeutic strategies targeting tumor microenvironment.</P>

역사문화콘텐츠를 활용한 철원지역 활성화 방안에 관한 연구 : 궁예와 태봉제를 중심으로

김진영(Kim, Megan Jin Young) 글로벌문화콘텐츠학회 2009 글로벌문화콘텐츠 Vol.0 No.3

궁예는 후삼국의 전란 속에서 천하제패를 꿈꾸었던 영걸이었으나 고려의 시조가 된 왕건에게 패한 군주로서 현재 남아있는 역사에서는 펌훼와 왜곡으로 그 실체에 다가서기가 쉽지 않다. 그러나 정사(正史)와는 달리 철원지역에 전해오는 많은 설화는 궁예가 폭압적이고 잔학한 군주가 아니라 불운한 영웅에 대한 지역민들의 측은지심을 느끼게 한다. 뿐만 아니라 지역곳곳에 흩어져 있는 궁예와 관련된 지명들은 백성들로부터 버림받은 폭군이 아니라, 오히려 사랑과 존경을 받은 왕으로 남아 있는 것을 반증한다고 볼 수 있다. Kung-ye is one of the most controversial figures in Korean history. However, it would not require verbose explanation of the fact that he was a hero with strong determination and capabilities, who proclaimed Later Koguryo (Hu Koguryo) at the height of internecine wars. In official history, Kung-ye was overthrown for misdemeanors and malpractice, yet on the contrary, many of the folk-tales and sagas originated from Cheorwon reflect that its residents demonstrate their sympathy for Kung-ye, not a tyrant but rather a very unfortunate king who was seemingly betrayed by the most reliable men of his own. Furthermore, the names of places in Cheorwon are historically related to Kung-ye and Taebong. Accordingly, it is inevitable to state that Kung-ye and his legacies are culturally remarkable prototypes in Cheorwon. With this favorable atmosphere, Cheorwon-gun has gotten into its stride in terms of developing cultural resources and historical heritages, such as Kung-ye Palace and the Taebong Festival, which are expected to lead Cheorwon to a more vitalizing community. Cheorwon is also exerting efforts to collect, analyze, and reassess data about Kung-ye for the purpose of straightening out its perpetually-denounced hero. In this context, this study was conducted to find ways to help invigorate regional economy by utilizing and conserving historical resources based on Kung-ye and Taebong.

Influencing Women's Actions on Cervical Cancer Screening and Treatment in Karawang District, Indonesia

Kim, Young-Mi,Ati, Abigael,Kols, Adrienne,Lambe, Fransisca Maria,Soetikno, Djoko,Wysong, Megan,Tergas, Ana Isabel,Rajbhandari, Presha,Lu, Enriquito Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Introduction: The impact of cervical cancer prevention programs depends on persuading women to go for screening and, if needed, treatment. As part of an evaluation of a pilot project in Indonesia, qualitative research was conducted to explore the factors that influence women's decisions regarding screening and treatment and to generate practical recommendations to increase service coverage and reduce loss to follow up. Methods: Research was conducted at 7 of the 17 public health centers in Karawang District that implemented the pilot project. Interviews and focus group discussions were held with 20 women, 20 husbands, 10 doctors, 18 midwives, 3 district health officials, and 16 advocacy team members. Results: Free services and mobile outreach events encouraged women to go for screening, along with promotional efforts by community health workers, advocacy teams, and the mass media. Knowledge and perceptions were the most important barriers to screening: women were not aware of cervical cancer risks, did not know the disease was treatable, and were fatalistic. Factors facilitating treatment were social support from husbands, relatives, and friends and the encouragement and role modeling of health workers. Barriers to prompt treatment included limited access to services and the requirement for husband's consent for cryotherapy. Conclusion: As cervical cancer prevention services are scaled up throughout Indonesia, the findings suggest three strategies to expand screening coverage and ensure prompt treatment: strengthening community mobilization and advocacy activities, modifying the service delivery model to encourage a single visit approach to screening and treatment, and working to gain men's support.

The Surgical Impact of E-Cigarettes: A Case Report and Review of the Current Literature

Megan Fracol,Robert Dorfman,Lindsay Janes,Swati Kulkarni,Kevin Bethke,Nora Hansen,John Kim 대한성형외과학회 2017 Archives of Plastic Surgery Vol.44 No.6

We report a case of a 51 years old female with a 25 pack year smoking history who underwent bilateral mastectomy and immediate tissue expander reconstruction for newly diagnosed right breast cancer. The patient reported herself as a non-smoker despite significant e-cigarette use, with resulting significant mastectomy skin flap necrosis and breast reconstruction failure. Little is known about the physiologic effect of e-cigarettes on wound healing and tissue perfusion. To this end, we provide an updated review of the impact of e-cigarettes on surgical outcomes. PubMed, Ovid MEDLINE, and PRS GO were searched for the terms “e-cigarette”, “electronic cigarette”, “e-cig”, “electronic nicotine delivery system”, “vaping”, “surgery”, “surgical”, “peri-operative”, “operate”, “operative”, and “wound healing”. Abstract review of all articles was performed. 123 articles returned that contained both variants of e-cigarettes and surgery as keywords. Of those, manual assessment returned three articles which were found to be relevant to e-cigarette use in the surgical patient. No articles were found that compared perioperative complications in e-cigarette versus traditional cigarette users in humans. In conclusion, our case report depicts the potential dangers associated with e-cigarette use in the surgical patient. There is a public misconception that e-cigarettes are healthier than traditional cigarettes and as such their use may go unreported by patients. Early evidence suggests e-cigarettes may induce some of the same physiologic changes as traditional cigarettes, and may have a significant deleterious effect on wound healing.

The Surgical Impact of E-Cigarettes: A Case Report and Review of the Current Literature

Fracol, Megan,Dorfman, Robert,Janes, Lindsay,Kulkarni, Swati,Bethke, Kevin,Hansen, Nora,Kim, John Korean Society of Plastic and Reconstructive Surge 2017 Archives of Plastic Surgery Vol.44 No.6

We report a case of a 51 years old female with a 25 pack year smoking history who underwent bilateral mastectomy and immediate tissue expander reconstruction for newly diagnosed right breast cancer. The patient reported herself as a non-smoker despite significant e-cigarette use, with resulting significant mastectomy skin flap necrosis and breast reconstruction failure. Little is known about the physiologic effect of e-cigarettes on wound healing and tissue perfusion. To this end, we provide an updated review of the impact of e-cigarettes on surgical outcomes. PubMed, Ovid MEDLINE, and PRS GO were searched for the terms "e-cigarette", "electronic cigarette", "e-cig", "electronic nicotine delivery system", "vaping", "surgery", "surgical", "peri-operative", "operate", "operative", and "wound healing". Abstract review of all articles was performed. 123 articles returned that contained both variants of e-cigarettes and surgery as keywords. Of those, manual assessment returned three articles which were found to be relevant to e-cigarette use in the surgical patient. No articles were found that compared perioperative complications in e-cigarette versus traditional cigarette users in humans. In conclusion, our case report depicts the potential dangers associated with e-cigarette use in the surgical patient. There is a public misconception that e-cigarettes are healthier than traditional cigarettes and as such their use may go unreported by patients. Early evidence suggests e-cigarettes may induce some of the same physiologic changes as traditional cigarettes, and may have a significant deleterious effect on wound healing.

Trehalose 6‐phosphate phosphatases of <i>Pseudomonas aeruginosa</i>

Cross, Megan,Biberacher, Sonja,Park, Suk‐,Youl,Rajan, Siji,Korhonen, Pasi,Gasser, Robin B.,Kim, Jeong‐,Sun,Coster, Mark J.,Hofmann, Andreas Federation of American Society for Experimental Bi 2018 The FASEB Journal Vol.32 No.10

Concurrent Isolation of 3 Distinct Cardiac Stem Cell Populations From a Single Human Heart Biopsy

Monsanto, Megan M.,White, Kevin S.,Kim, Taeyong,Wang, Bingyan J.,Fisher, Kristina,Ilves, Kelli,Khalafalla, Farid G.,Casillas, Alexandria,Broughton, Kathleen,Mohsin, Sadia,Dembitsky, Walter P.,Sussman, Grune & Stratton 2017 Circulation research Vol.121 No.2

<P><B><U>Rationale:</U></B></P><P>The relative actions and synergism between distinct myocardial-derived stem cell populations remain obscure. Ongoing debates on optimal cell population(s) for treatment of heart failure prompted implementation of a protocol for isolation of multiple stem cell populations from a single myocardial tissue sample to develop new insights for achieving myocardial regeneration.</P><P><B><U>Objective:</U></B></P><P>Establish a robust cardiac stem cell isolation and culture protocol to consistently generate 3 distinct stem cell populations from a single human heart biopsy.</P><P><B><U>Methods and Results:</U></B></P><P>Isolation of 3 endogenous cardiac stem cell populations was performed from human heart samples routinely discarded during implantation of a left ventricular assist device. Tissue explants were mechanically minced into 1 mm<SUP>3</SUP> pieces to minimize time exposure to collagenase digestion and preserve cell viability. Centrifugation removes large cardiomyocytes and tissue debris producing a single cell suspension that is sorted using magnetic-activated cell sorting technology. Initial sorting is based on tyrosine-protein kinase Kit (c-Kit) expression that enriches for 2 c-Kit<SUP>+</SUP> cell populations yielding a mixture of cardiac progenitor cells and endothelial progenitor cells. Flowthrough c-Kit<SUP>−</SUP> mesenchymal stem cells are positively selected by surface expression of markers CD90 and CD105. After 1 week of culture, the c-Kit<SUP>+</SUP> population is further enriched by selection for a CD133<SUP>+</SUP> endothelial progenitor cell population. Persistence of respective cell surface markers in vitro is confirmed both by flow cytometry and immunocytochemistry.</P><P><B><U>Conclusions:</U></B></P><P>Three distinct cardiac cell populations with individualized phenotypic properties consistent with cardiac progenitor cells, endothelial progenitor cells, and mesenchymal stem cells can be successfully concurrently isolated and expanded from a single tissue sample derived from human heart failure patients.</P>

Activated T Cells Secrete an Alternatively Spliced Form of Common γ-Chain that Inhibits Cytokine Signaling and Exacerbates Inflammation

Hong, C.,Luckey, Megan A.,Ligons, Davinna L.,Waickman, Adam T.,Park, J.Y.,Kim, Grace Y.,Keller, Hilary R.,Etzensperger, R.,Tai, X.,Lazarevic, V.,Feigenbaum, L.,Catalfamo, M.,Walsh, Scott T.R.,Park, J. Cell Press 2014 Immunity Vol.40 No.6

The common γ-chain (γc) plays a central role in signaling by IL-2 and other γc-dependent cytokines. Here we report that activated T cells produce an alternatively spliced form of γc mRNA that results in protein expression and secretion of the γc extracellular domain. The soluble form of γc (sγc) is present in serum and directly binds to IL-2Rβ and IL-7Rα proteins on T cells to inhibit cytokine signaling and promote inflammation. sγc suppressed IL-7 signaling to impair naive T cell survival during homeostasis and exacerbated Th17-cell-mediated inflammation by inhibiting IL-2 signaling upon T cell activation. Reciprocally, the severity of Th17-cell-mediated inflammatory diseases was markedly diminished in mice lacking sγc. Thus, sγc expression is a naturally occurring immunomodulator that regulates γc cytokine signaling and controls T cell activation and differentiation.

A Pulse Check on General Public’s Knowledge, Awareness, and Attitudes towards Liver Health in South Korea

( Hye Won Lee ),( Jin Youn ),( Megan Kim ),( Shikha Singh ),( Sang Hoon Ahn ) 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Ikaros is required to survive positive selection and to maintain clonal diversity during T-cell development in the thymus

Tinsley, Kevin W.,Hong, Changwan,Luckey, Megan A.,Park, Joo-Young,Kim, Grace Y.,Yoon, Hee-won,Keller, Hilary R.,Sacks, Andrew J.,Feigenbaum, Lionel,Park, Jung-Hyun American Society of Hematology 2013 Blood Vol.122 No.14

<P>The zinc-finger protein Ikaros is a key player in T-cell development and a potent tumor suppressor in thymocytes. To understand the molecular basis of its function, we disabled Ikaros activity in vivo using a dominant negative Ikaros transgene (DN-IkTg). In DN-IkTg mice, T-cell development was severely suppressed, and positively selected thymocytes clonally expanded, resulting in a small thymus with a heavily skewed T-cell receptor (TCR) repertoire. Notably, DN-IkTg induced vigorous proliferation concomitant to downregulation of antiapoptotic factor expression such as Bcl2. Ikaros activity was required during positive selection, and specifically at the CD4<SUP>+</SUP>CD8<SUP>lo</SUP> intermediate stage of thymocyte differentiation, where it prevented persistent TCR signals from inducing aberrant proliferation and expansion. In particular, DN-IkTg induced the accumulation of CD4 single-positive (SP) thymocytes with a developmentally transitional phenotype, and it imposed a developmental arrest accompanied by massive apoptosis. Thus, we identified an in vivo requirement for Ikaros function, which is to suppress the proliferative potential of persistent TCR signals and to promote the survival and differentiation of positively selected thymocytes.</P>